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206 Study Matches
Canakinumab for the Prevention of Progression to Cancer in Patients With Clonal Cytopenias of Unknown Significance, IMPACT Study
This phase II trial tests how well canakinumab works to prevent progression to cancer in patients with clonal cytopenias of unknown significance (CCUS). CCUS is a blood condition defined by a decrease in blood cells. Blood cells are composed of either red blood cells, white blood cells, or platelets. In patients with CCUS, blood counts have been low for a long period of time. Patients with CCUS also have a mutation in one of the genes that are responsible for helping blood cells develop. The combination of genetic mutations and low blood cell counts puts patients with CCUS at a higher risk to develop blood cancers in the future. This transformation from low blood cell counts to cancer may be caused by inflammation in the body. Canakinumab is a monoclonal antibody that may block inflammation in the body by targeting a specific antibody called the anti-human interleukin-1beta (IL-1beta).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years to old
PHASE2
NCT05641831
STU-2024-0699
Inclusion Criteria:
* Patients with age \>= 18 with high-risk CCUS
* Must meet ALL the following criteria:
* Unexplained, clinically meaningful cytopenias (greater than 4 months) in one or more of the following lineages: erythroid cells, neutrophils, platelets. Clinically meaningful cytopenia is institution specific and threshold may vary on age, sex, and race. Decision-making should depend upon lab values specific to the institution and supersede public works. Based upon published work, significant cytopenias are defined as the following (must meet criteria in at least one lineage):
* Erythroid Cells:
* Hemoglobin \< 11 g/dL
* White Blood Cells:
* Absolute Neutrophil Count \< 1800/microL and \> 500/microL
* Platelets:
* Platelet Count \< 150,000/microL and \> 50,000/microL
* MDS criteria not fulfilled
* No other evidence of hematological malignancy
* No or only mild (\< 10%) bone marrow dysplasia
* Blast cells \< 5% detected via morphologic examination of blood and/or bone marrow smears which can also be supported by flow cytometry and/or immunohistochemical studies
* Any of the following:
* Isolated somatic spliceosome mutation at any VAF (SRSF2, SF3B1, U2AF1, or ZRSR2)
* Isolated TP53 mutation greater than 5% VAF
* At least 1 mutation in TET2, DMNT3A, or ASXL1 at any VAF coupled with at least 1 other known myeloid pathogenic somatic mutation or known pathogenic germline mutation that predisposes to myeloid malignancy as determined by next generation sequencing and bone marrow biopsy
* A TET2, DMNT3A, or ASXL1 greater than 10% VAF coupled with another TET2, DMNT3A, or ASXL1 greater than 10% VAF
* The presence of two or more known myeloid pathogenic somatic or germline mutations (other than TET2, ASXL1, DMNT3A, TP53, or spliceosome mutations) greater than 10% VAF
* Ability to understand and willingness to sign the written informed consent document
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
* Patients with a history of hypertension or active hypertension are strongly encouraged to optimize blood pressure control
* Creatinine clearance greater than 45 ml/min using Cockcroft-Gault
* Total bilirubin =\< 1.5 x ULN
* Aspartate transaminase (AST) \< 3 x ULN
* Alanine transaminase (ALT) \< 3 x ULN
Exclusion Criteria:
* Concurrent malignancy requiring active systemic therapy
* Diagnosis of MDS or any other myeloid malignancy in the patient's lifetime
* History of Hypersensitivity to canakinumab or drug of a similar class
* Active infection requiring prompt evaluation and treatment or history of recurrent infections
* Known active or recurrent hepatic disorder including cirrhosis, hepatitis B and C (via positive or indeterminate central laboratory \[lab\] results)
* Subjects with active tuberculosis. In subjects with a history of tuberculosis but without active tuberculosis, if the results of the evaluation require treatment per local guidelines, then the treatment should be initiated before randomization (unless otherwise required by Health Authorities or Institutional Review Board (IRB) in which case curative treatment must be completed prior to screening)
* Subjects with suspected or proven immunocompromised state or infections. If the results of this screening per local treatment guidelines or clinical practice require treatment for said infection then the patient is not eligible. Suspected or proven immunocompromised states or infections include:
* Those with any other medical condition such as active infection, treated or untreated, which in the opinion of the investigator places the subject at an unacceptable risk for participation in immunomodulatory therapy. If in the opinion of the investigator, the patient's immunocompromised state does not pose an unacceptable risk for participation, in the absence of uncontrolled infection, and the patient does not have a history of serious infections (such as tuberculosis); then the patient may participate in this study.
* Known history of testing positive for human immunodeficiency virus (HIV) infections. For countries where HIV status is mandatory: testing positive for HIV during screening using a local test.
* Allogeneic bone marrow or solid organ transplant (history of any or within a certain period of time?)
* Those requiring systemic or local treatment in doses with systemic effects e.g.:
* Prednisone \> 20 mg (or equivalent) oral or intravenous daily for \> 14 days
* Prednisone \> 5 mg and =\< 20 mg (or equivalent) daily for \> 30 days
* Equivalent dose of methotrexate \> 15 mg weekly
* Note: Azathioprine is allowed. Daily glucocorticoid-replacement for conditions such as adrenal or pituitary insufficiency is allowed. Topical, inhaled or local steroid use in doses that are not considered to cause systemic effects are permitted. Steroids for pre-medication related to chemotherapy as per local standard of care are permitted.
* Live or attenuated vaccination within 3 months prior to first dose of study drug (e.g. Measles/Mumps/Rubella \[MMR\], Yellow Fever, Rotavirus, Smallpox, etc.) and after initiation of canakinumab treatment
* Use of erythropoietin stimulating agents (ESA) or growth factors within four weeks prior to the start of the study
* Pregnant or nursing women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using basic methods of contraception during dosing of study treatment and for up to 130 days after last dose of study drug. Basic contraception methods include:
* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least 6 weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
* Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject
* Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps). For UK: with spermicidal foam/gel/film/cream/ vaginal suppository
* Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate \< 1%), for example hormone vaginal ring or transdermal hormone contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS). In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Prior to entry into this study, cisplatin-based chemotherapy, which may be toxic to the fetus, may be given. The time between the end of cisplatin-based chemotherapy and the start canakinumab/placebo treatment is variable, resulting in a variable need for continuation of highly effective contraception. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (i.e. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks prior to first dose of study drug. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the Informed Consent Form (ICF). PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration and Biopsy, DRUG: Canakinumab, PROCEDURE: Chest Radiography, PROCEDURE: Echocardiography, DRUG: Placebo Administration, OTHER: Quality-of-Life Assessment
Clonal Cytopenia of Undetermined Significance, Myeloid and Monocytic Leukemia, Leukemia, Not Otherwise Specified, Leukemia, Other
UT Southwestern
A Multi-Institution Study of TGFβ Imprinted, Ex Vivo Expanded Universal Donor NK Cell Infusions as Adoptive Immunotherapy in Combination With Gemcitabine and Docetaxel in Patients With Relapsed or Refractory Pediatric Bone and Soft Tissue (TINKS)
The purpose of this study is to determine if the addition of infusions of a type of immune cell called a "natural killer", or NK cell to the sarcoma chemotherapy regimen GEM/DOX (gemcitabine and docetaxel) can improve outcomes in people with childhood sarcomas that have relapsed or not responded to prior therapies. The goals of this study are: * To determine the safety and efficacy of the addition of adoptive transfer of universal donor, TGFβ imprinted (TGFβi), expanded NK cells to the pediatric sarcoma salvage chemotherapeutic regimen gemcitabine/docetaxel (GEM/DOX) for treatment of relapsed and refractory pediatric sarcomas To determine the 6-month progression free survival achieved with this treatment in patients within cohorts of relapsed or refractory osteosarcoma, Ewing sarcoma, rhabdomyosarcoma and non-rhabdomyosarcoma soft tissue sarcoma. * To identify toxicities related to treatment with GEM/DOX + TGFβi expanded NK cells Participants will receive study drugs that include chemotherapy and NK cells in cycles; each cycle is 21 days long and you can receive up to 8 cycles. * Gemcitabine (GEM): via IV on Days 1 and 8 * Docetaxel (DOX): via IV on Day 8 * Prophylactic dexamethasone: Day 7-9 to prevent fluid retention and hypersensitivity reaction * Peg-filgrastim (PEG-GCSF) or biosimilar: Day 9 to help your white blood cell recover and allow more chemotherapy to be given * TGFβi NK cells: via IV on Day 12
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Avanthi Shah
ALL
2 Years to 40 Years old
PHASE1
NCT05634369
STU-2023-0706
Inclusion Criteria:
• Patients must be between the ages ≥ 2 years and ≤ 40 years of age and have had a relapsed or refractory osteosarcoma, Ewing sarcoma, rhabdomyosarcoma or non-rhabdomyosarcoma soft tissue sarcoma.
• Patients must have measurable disease using RECIST 1.1 criteria
• Patients must have had at least one and no more than four total lines of cytotoxic systemic treatment for relapse sarcoma. Local control with surgical resection or radiation therapy of the primary tumor and any metastatic sites as clinically indicated as standard of care per the treating physician must be considered prior to enrollment.
• Prior Therapy: Therapy may not have been received more recently than the timeframes defined below: * Myelosuppressive chemotherapy: Patients must not have received myelosuppressive therapy within 14 days of protocol therapy * Radiation: At least 2 weeks must have elapsed from the start of protocol therapy since local palliative XRT (small port); 4 weeks must have elapsed for all other radiation therapy * Hematopoietic Cell Transplant (HCT): Patients must have at least 6 weeks elapsed after autologous and allogeneic hematopoietic cell transplant * Biologic (anti-neoplastic agent): At least 7 days or 5 half-lives of the drug, whichever is longer, must have elapsed from the start of protocol therapy since the completion of therapy with a biologic agent. * Monoclonal antibodies: At least 3 weeks must have elapsed from the start of protocol therapy since prior therapy that included a monoclonal antibody. * Prior use of Gemcitabine and/or Docetaxel: Patients who have received these agents for prior treatment may be included if previous treatments were given ≥ 6 months prior to enrollment on this study, and there were no allergic reactions, pulmonary edema or fibrosis, Grade 3 or higher neuropathy or other non-hematologic Grade 4 adverse events related to gemcitabine and/or docetaxel therapies. 4\) Performance status: Karnofsky ≥ 60 for patients ≥16 years of age. Lansky score of ≥ 60 for patients \< 16 years of age (see Appendix A) 5) Organ Function Requirements: Patients must have normal organ and marrow function within 7 days of starting protocol therapy as defined below: * Absolute Neutrophil Count ≥1000/mcL * Platelet count ≥100,000/mcL transfusion independent defined as no platelet transfusions within the last 72 hours * Total bilirubin \< 1.5x upper limit of normal for age * AST(SGOT)/ALT(SGPT) ≤ 2.5 x institutional upper limit of normal * Serum creatinine \< 1.5 x upper limit of normal based on age/gender (Table 3) OR creatinine clearance ≥70 mL/min/1.73 m2 for patients with creatinine levels above institutional normal * Shortening fraction ≥ 27% by ECHO OR ejection fraction of ≥ 50% by ECHO or gated radionuclide study * Echocardiogram done within 12 months of study entry will be acceptable. If patient has required anthracycline chemotherapy since last ECHO and enrollment on this study, echocardiogram should be repeated. * No evidence for dyspnea at rest, no chronic oxygen requirement, and room air pulse oximetry \>94% if there is a clinical indication for pulse oximetry 6) Neuropathy: Patients must have ≤ Grade 2 neuropathy at enrollment 7) Patients with seizure disorders may be enrolled if seizures are well controlled on anti-convulsant, with the exception of diazepam given its potential deleterious effects on NK cell activity. 8\) Contraception: The effects of expanded NK cells on the developing human fetus are unknown. For this reason and because the chemotherapeutic preparative agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of preparatory regimen administration. 9\) All patients and/or their parents or legal guardians must have the ability to understand and the willingness to sign a written informed consent/assent document.
Exclusion Criteria:
• Patients who are receiving any other investigational agents.
• Patients must not be receiving any additional medicines being given for the specific purpose of treating cancer
• Patients with a history of allergic reactions attributed to docetaxel, gemcitabine, or peg-filgrastim or biosimilar
• Patients who have received any prior cellular therapies, such as CAR-T cells or other expanded or manufactured cellular products.
• Patients with bone marrow only disease are not eligible for this study.
• Patients with any of the following "Intermediate" (rarely metastasizing) or "malignant" Grade 2 or Grade 3 tumors of any size, as defined in the WHO Classification of Soft Tissue Tumors are not eligible for this study: * So-called fibrohistiocytic tumors - plexiform fibrohistiocytic tumor, giant cell tumor of soft tissues * Fibroblastic/myofibroblastic tumors - solitary fibrous tumor, malignant solitary fibrous tumor, inflammatory myofibroblastic tumor, low grade myofibroblastic sarcoma, myxoinflammatory fibroblastic sarcoma, atypical myxoinflammatory fibroblastic tumor, myxofibrosarcoma, low grade fibromyxoid sarcoma, sclerosing epithelioid fibrosarcoma * Tumors of uncertain differentiation - epithelioid sarcoma, alveolar soft part sarcoma, clear cell sarcoma of soft tissue, angiomatoid fibrous histiocytoma, ossifying fibromyxoid tumour, myoepithelioma, myoepithelial carcinoma, extraskeletal myxoid chondrosarcoma, neoplasms with perivascular epithelioid cell differentiation (PEComa), initial sarcoma, atypical fibroxanthoma, mixed tumor NOS, phosphaturic mesenchymal tumor, malignant ossifying fibromyxoid tumor, malignant mixed tumor, malignant phosphaturic mesenchymal tumor * Chondro-osseous tumors - extraskeletal osteosarcoma * Pericytic (perivascular) tumors - malignant glomus tumor * Nerve sheath tumors - malignant peripheral nerve sheath tumor, malignant granular cell tumor, epithelioid malignant peripheral nerve sheath tumor, malignant Triton tumor * Undifferentiated sarcomas (with a specific pathologic category in the WHO classification) - undifferentiated round cell sarcoma, undifferentiated epithelioid sarcoma, undifferentiated spindle cell sarcoma
• Patients who, in the judgment of the treating physician, has tumors near critical structures for which transient swelling would cause substantial symptoms, such as tumor within the bowel mucosa
• Patients with CNS metastatic disease will not be eligible for this study.
• Concomitant Medications: * Due to their effect on NK cell function, systemic corticosteroids outside of the supportive dexamethasone given from day 7 through 9 should be used ONLY for life-threatening conditions (i.e., life-threatening allergic reactions and anaphylaxis such as bronchospasm, stridor) unresponsive to other measures. The use of dexamethasone as an anti-emetic is not permitted. Corticosteroid therapy can be used as a premedication for transfusion in patients known to have a history of transfusion reactions or for treatment of an unexpected transfusion reaction (hydrocortisone 2 mg/kg or less or an equivalent dose of an alternative corticosteroids). The use of steroids during protocol therapy other than the study- required prophylactic dexamethasone doses requires clear justification and documentation of use for a life-threatening condition. * The following are also prohibited while on study treatment * Strong CYP3A4 inducers. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/; medical reference texts such as the Physicians' Desk Reference may also provide this information. * Diazepam * Chemotherapeutic agents other than the study drugs
• Uncontrolled intercurrent illness including, but not limited to: * ongoing or active infection * psychiatric illness/social situations that would limit compliance with study requirements
• Pregnancy or Breast-Feeding: Pregnant or breast-feeding woman will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies with Gemcitabine and Docetaxel
• HIV Infection: HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the study medications. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
BIOLOGICAL: GEM/DOX + TGFBi expanded NK cells
Pediatric Sarcoma, Refractory, Pediatric Sarcoma, Relapsed, Bones and Joints, Sarcoma, Soft Tissue
Children’s Health
FORAGER-1: A Study of LOXO-435 (LY3866288) in Participants With Cancer With a Change in a Gene Called FGFR3 (FORAGER-1)
The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-435 by itself or when it is combined with other standard medicines that treat cancer. LOXO-435 may be used to treat cancer of the cells that line the urinary system and other solid tumor cancers that have a change in a particular gene (known as the FGFR3 gene). Participation could last up to 30 months (2.5 years) and possibly longer if the disease does not get worse.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years and over
PHASE1
NCT05614739
STU-2023-0080
Inclusion Criteria:
* Have solid tumor cancer with an FGFR3 pathway alteration on molecular testing in tumor or blood sample that is deemed as actionable
* Cohort A1: Presence of an alteration in FGFR3 or its ligands
* Cohort A2, B2, B3, and B5: Histological diagnosis of urothelial cancer (UC) that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration
* Cohorts B1 and B4: Histological diagnosis of urothelial cancer that is locally advanced or metastatic
* Cohort C1: Must have histological diagnosis of a non-urothelial solid tumor malignancy that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration
* Measurability of disease:
* Cohort A1 and B3: Measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST v1.1)
* Cohorts A2, B1, B2, B4, B5, and C1: Measurable disease required as defined by RECIST v1.1
* Have adequate tumor tissue sample available. Participants with inadequate tissue sample availability may still be considered for enrollment upon review
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 for Cohorts A1, A2, B3, and B5
* Less than or equal to 2 for Cohorts B1, B2, B4, and C1
* Prior Systemic Therapy Criteria:
* Cohort A1/C1: Participant has received all standard therapies for which the participant was deemed to be an appropriate candidate by the treating Investigator; OR the participant is refusing the remaining most appropriate standard of care treatment; OR there is no standard therapy available for the disease. There is no restriction on number of prior therapies.
* Cohort A2, B2, B3 participants must have received at least one prior regimen, and cohorts B1 and B4 participants at least 2 prior regimens, in the locally advanced or metastatic setting
* There is no restriction on number of prior therapies
* Cohort B5: Participants have not received prior systemic therapy for locally advanced or metastatic UC
* FGFR inhibitor specific requirements:
* Cohort A1/A2/B3: Prior FGFR inhibitor treatment is permitted but not required
* Cohort B1/B4: Participants must have been previously treated with erdafitinib
* Cohort B2, B5, and C1: Participants must be FGFR inhibitor naïve
Exclusion Criteria:
* Participants with primary central nervous system (CNS) malignancy
* Untreated or uncontrolled CNS metastases
* Current evidence of corneal keratopathy or retinal disorder. Individuals with asymptomatic ophthalmic conditions may be eligible
* Any serious unresolved toxicities from prior therapy
* Significant cardiovascular disease
* Prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF)
* Active uncontrolled systemic infection or other clinically significant medical conditions
* Participants who are pregnant, lactating, or plan to breastfeed during the study or within 6 months of the last dose of study treatment. Participants who have stopped breastfeeding may be enrolled DRUG: LOXO-435, DRUG: Pembrolizumab, DRUG: enfortumab vedotin
Urinary Bladder Neoplasms, Neoplasm Metastasis, Ureteral Neoplasms, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Kaposis sarcoma, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Unknown Sites, Urinary Bladder
Bladder Cancer, Bladder Urothelial Carcinoma, Urinary Bladder Cancer, Urinary Tract Cancer, Renal Pelvis Cancer, Ureter Cancer
UT Southwestern; Parkland Health & Hospital System
Selinexor in Maintenance Therapy After Systemic Therapy for Participants With p53 Wild-Type, Advanced or Recurrent Endometrial Carcinoma (XPORT-EC-042)
The purpose of this study is to evaluate the efficacy and safety of selinexor as a maintenance treatment in patients with p53 wt endometrial carcinoma (EC), who have achieved a partial response (PR) or complete response (CR) (per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v 1.1\]) after completing at least 12 weeks of platinum-based therapy. A total of 276 participants will be enrolled in the study and randomized in a 1:1 ratio to maintenance therapy with either selinexor or placebo.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Miller
ALL
18 Years and over
PHASE3
NCT05611931
STU-2023-0654
Inclusion Criteria:
Patients must meet all of the following inclusion criteria in order to be eligible to participate in this study:
* Adults (Aged ≥ 18 years)
* Histologically confirmed endometrial cancer (endometrioid, serous, undifferentiated, or carcinosarcoma sub-types) that is TP53 wild type by central NGSHistologically confirmed EC including endometrioid, serous, undifferentiated, and carcinosarcoma
* Must have completed at least 12 weeks of platinum-based chemotherapy (with or without immune checkpoint inhibitors), with a confirmed partial or complete response according to RECIST v1.1
* Must be able to initiate C1D1 within 3-8 weeks after last platinum dose
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Adequate bone marrow function and organ function
Exclusion Criteria:
Patients meeting any of the following exclusion criteria are not eligible to participate in this study:
* Uterine sarcomas, clear cell or small cell carcinoma with neuroendocrine differentiation
* Palliative radiotherapy administered within 14 days of intended C1D1
* Any gastrointestinal dysfunction that could interfere with the absorption of oral study therapy
* Serious psychiatric or medical conditions that could interfere with study participation or would make study involvement unreasonably hazardous
* Previous treatment with an XPO1 inhibitor
* Stable disease or disease progression after platinum-based chemotherapy
* Pregnancy, breastfeeding, or other legal/ethical restrictions to trial participation
* Known dMMR/MSI-H EC tumors that are medically eligible to receive an immune checkpoint inhibitor DRUG: Selinexor, DRUG: Matching Placebo for selinexor
Endometrial Cancer, Corpus Uteri
Selinexor, KPT-330, Advanced or Recurrent Endometrial Carcinoma, XPORT-EC, ENGOT-EN20, GOG-3083, XPORT-EC-042, p53 wild-type, Tumor protein 53 wild-type
UT Southwestern; Parkland Health & Hospital System
Study to Compare Axicabtagene Ciloleucel With Standard of Care Therapy as First-line Treatment in Participants With High-risk Large B-cell Lymphoma (ZUMA-23)
The goal of this clinical study is to compare the study drug, axicabtagene ciloleucel, versus standard of care (SOC) in first-line therapy in participants with high-risk large B-cell lymphoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Praveen Ramakrishnan Geethakumari
ALL
18 Years and over
PHASE3
NCT05605899
STU-2023-0133
Key
Inclusion Criteria:
* Histologically confirmed large B cell lymphoma (LBCL) based on 2016 World Health Organization (WHO) classification by local pathology lab assessment, including of the following:
* Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS)
* High-grade B-cell lymphoma (HGBL)
* Note: Transformed DLBCL from follicular lymphoma or from marginal zone lymphoma is eligible if no prior treatment with anthracycline-containing regimen.
* High-risk disease defined as an International Prognostic Index (IPI) score of 4 or 5 at initial diagnosis.
* Have received only 1 cycle of rituximab plus chemotherapy (R-chemotherapy).
* Adequate bone marrow, renal, hepatic, pulmonary, and cardiac function.
* Females of childbearing potential must have a negative serum or urine pregnancy test.
Key Exclusion Criteria:
* The following WHO 2016 subcategories by local assessment:
* T-cell/histiocyte-rich LBCL
* Primary DLBCL of the central nervous system (CNS)
* Primary mediastinal (thymic) LBCL
* B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma
* Burkitt lymphoma
* History of Richter's transformation of chronic lymphocytic leukemia
* Presence of detectable cerebrospinal fluid (CSF)-malignant cells, brain metastases, or a history of CNS involvement of lymphoma.
* Presence of cardiac lymphoma involvement.
* Any prior treatment for LBCL other than the 1 cycle of R-chemotherapy.
* History of severe immediate hypersensitivity reaction to any of the agents used in this study.
* Presence of CNS disorder. History of stroke, transient ischemic attack, or posterior reversible encephalopathy syndrome (PRES) within 12 months prior to enrollment.
* History of acute or chronic active hepatitis B or C infection.
* Positive for human immunodeficiency virus (HIV) unless taking appropriate anti-HIV medications, with an undetectable viral load by PCR and with a cluster of differentiation 4 (CD4) count \> 200 cells/uL.
* Medical conditions or residual toxicities from prior therapies likely to interfere with assessment of safety or efficacy of study treatment. Please refer to protocol for further details.
* History of clinically significant cardiac disease within 12 months before enrollment.
* History of any medical condition requiring maintenance systemic immunosuppression/systemic disease modifying agents within the last 2 years.
Note: Other protocol defined Inclusion/Exclusion criteria may apply. BIOLOGICAL: Axicabtagene Ciloleucel, DRUG: Cyclophosphamide, DRUG: Fludarabine, DRUG: Etoposide, DRUG: Rituximab, DRUG: Doxorubicin, DRUG: Vincristine, DRUG: Prednisone
High-risk Large B-cell Lymphoma (LBCL), Non-Hodgkins Lymphoma, Other Hematopoietic, Soft Tissue
UT Southwestern
Studying the Effect of Levocarnitine in Protecting the Liver From Chemotherapy for Leukemia or Lymphoma
This phase III trial compares the effect of adding levocarnitine to standard chemotherapy versus (vs.) standard chemotherapy alone in protecting the liver in patients with leukemia or lymphoma. Asparaginase is part of the standard of care chemotherapy for the treatment of acute lymphoblastic leukemia (ALL), lymphoblastic lymphoma (LL), and mixed phenotype acute leukemia (MPAL). However, in adolescent and young adults (AYA) ages 15-39 years, liver toxicity from asparaginase is common and often prevents delivery of planned chemotherapy, thereby potentially compromising outcomes. Some groups of people may also be at higher risk for liver damage due to the presence of fat in the liver even before starting chemotherapy. Patients who are of Japanese descent, Native Hawaiian, Hispanic or Latinx may be at greater risk for liver damage from chemotherapy for this reason. Carnitine is a naturally occurring nutrient that is part of a typical diet and is also made by the body. Carnitine is necessary for metabolism and its deficiency or absence is associated with liver and other organ damage. Levocarnitine is a drug used to provide extra carnitine. Laboratory and real-world usage of the dietary supplement levocarnitine suggests its potential to prevent or reduce liver toxicity from asparaginase. The overall goal of this study is to determine whether adding levocarnitine to standard of care chemotherapy will reduce the chance of developing severe liver damage from asparaginase chemotherapy in ALL, LL and/or MPAL patients.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kathleen Ludwig
ALL
15 Years to 40 Years old
PHASE3
NCT05602194
STU-2023-1026
Inclusion Criteria:
* \>= 15 and \< 40 years at time of diagnosis
* Newly diagnosed B-ALL, T-ALL, lymphoblastic lymphoma (LLy), or mixed-phenotype acute leukemia/lymphoma (MPAL)
* Note: Philadelphia chromosome (PH)+ and PH-like acute leukemia are eligible (use of tyrosine kinase inhibitors \[TKI\] or CRLF2- targeted concomitant medication must be documented, if used)
* Conjugated bilirubin =\< 1.5 x upper limit of normal (ULN) for age, regardless of baseline bilirubin (within 7 days prior to enrollment), and
* Serum glutamate pyruvate transaminase (SGPT) (ALT) =\< 225 U/L (=\< 5x ULN) (within 7 days prior to enrollment), and
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L and serum glutamic oxaloacetic transaminase (SGOT) (AST) to 50 U/L regardless of baseline
* SGOT (AST) =\< 250 U/L (=\< 5x ULN) (within 7 days prior to enrollment)
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L and SGOT (AST) to 50 U/L regardless of baseline
* For patients receiving ursodiol prior to enrollment, laboratory values must meet above criteria off ursodiol for 7 days
* PEDIATRIC PATIENTS (AGE 15-17 years):
* A 24-hour urine creatinine clearance \>= 30 mL/min/1.73 m\^2 (within 7 days prior to enrollment) OR
* A glomerular filtration rate (GFR) \>= 30 mL/min/1.73 m\^2. GFR must be performed using one of the following methods (within 7 days prior to enrollment):
* 1\. Estimated GFR (eGFR) \>= 30 mL/min/1.73 m\^2.
* An online calculator is available through the National Kidney Foundation at https://www.kidney.org/professionals/kdoqi/gfr\_calculatorped
* 2\. Measured GFR \>= 30 mL/min/1.73 m\^2 (any age). If measured GFR is used, it must be performed using direct measurement with a nuclear blood sampling method or small molecule clearance method (iothalamate or other molecule per institutional standard).
* ADULT PATIENTS (AGE 18 YEARS OR OLDER): Creatinine clearance \>= 30 mL/min, as estimated by the Cockcroft and Gault formula or a 24-hour urine collection (within 7 days prior to enrollment). Estimated creatinine clearance is based on actual body weight
* An online calculator is available through the National Kidney Foundation at https://www.kidney.org/professionals/kdoqi/gfr\_calculatorcoc
* Berlin-Frankfurt-Munich (BFM), Children's Oncology Group (COG), or C10403-based Induction regimen and must be inclusive of \>= 1 dose of pegaspargase or calaspargase pegol, and
* First dose of asparaginase must be planned within the first week of induction therapy, and
* Dose of pegaspargase or calaspargase pegol must be \>= 1,000 IU/ m\^2 (dose-capping permitted per primary regimen)
* Note: Co-enrollment on a therapeutic consortia trial is not required
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
* Down syndrome
* Known inherited or autoimmune liver disease impacting conjugated bilirubin (e.g., Alagille syndrome, primary sclerosing cholangitis, other)
* Known biopsy (or imaging) proven severe liver fibrosis (Batts-Ludwig \>= stage 3)
* Unable to tolerate oral formulation of study drug at enrollment
* Patients who received chemotherapy or treatment for a prior malignancy are not eligible
* The following are permitted: steroid prophase, hydroxyurea, or other cytoreduction prior to initiation of Induction chemotherapy (must be documented) and chemotherapy for current diagnosis (i.e. initiation of Induction therapy within enrollment window). Chemotherapy prior to enrollment for treatment of a non-malignancy (e.g., steroid or methotrexate for autoimmune disease) is also permitted and must be documented
* Female patients who are pregnant since fetal toxicities and teratogenic effects in humans are unknown for study drug. A pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation PROCEDURE: Biospecimen Collection, DRUG: Calaspargase Pegol, DIETARY_SUPPLEMENT: Levocarnitine, DRUG: Pegaspargase, OTHER: Quality-of-Life Assessment
B Acute Lymphoblastic Leukemia, B Acute Lymphoblastic Leukemia With t(9,22)(q34.1,q11.2), BCR-ABL1, B Acute Lymphoblastic Leukemia, BCR-ABL1-Like, Lymphoblastic Lymphoma, Mixed Phenotype Acute Leukemia, T Acute Lymphoblastic Leukemia, Lymphoid Leukemia, Lymphoma
Children’s Health
A Phase 2a, Single-dose, Open-label Study to Evaluate Diagnostic Performance and Safety of Pegsitacianine, an Intraoperative Fluorescence Imaging Agent for the Detection of Cancer, in Patients With Unknown Primary Head and Neck Cancer (ILLUMINATE STUDY)
This is a non-randomized, open-label, single-center, safety and imaging feasibility study of Pegsitacianine, an intraoperative fluorescence imaging agent.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Baran Sumer
ALL
18 Years to 99 Years old
PHASE2
NCT05576974
STU-2022-0460
Inclusion Criteria:
• Adults ≥18 years of age
• Biopsy-confirmed diagnosis, for primary or recurrent disease (or high clinical suspicion in the opinion of the Investigator)
• Part 1: Stage 1 to 4 HNSCC
• Part 2: UPC squamous cell carcinoma of the head and neck with metastatic disease to at least a single cervical node, AND no biopsy proven evidence of the primary cancer's location.
• Acceptable hematologic status (as standard surgery protocol requires, as determined by the Investigator), kidney function and liver function. Elevations of creatinine, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or total bilirubin \>1.5× the upper limit of normal \[ULN\] must be determined to be not clinically significant by the Investigator and approved by the Medical Monitor.
• Documented negative serum pregnancy test for women of childbearing potential (i.e., premenopausal women with intact reproductive organs and women \<2 years after menopause)
• Male patients and female patients of child-bearing potential (i.e., premenopausal women with intact reproductive organs and women \<2 years after menopause) must agree to and comply with using medically acceptable contraception including surgical sterilization (e.g., hysterectomy, bilateral oophorectomy, bilateral tubal ligation), intrauterine device, oral contraceptive, contraceptive patch, long acting injectable contraceptive, partner's vasectomy, double-barrier method (condom or diaphragm plus spermicide or condom plus diaphragm), or abstinence during the trial and for 6 months thereafter
• Agree to abstain from alcohol consumption from 72 hours before Pegsitacianine administration through completion of Study Day 10 (±48 hours) visit in Part 1 and Part 2.
• Adequate potential for follow up
Exclusion Criteria:
• Tumors at sites of which the surgeon would assess that in vivo intraoperative imaging would not be feasible.
• Life expectancy \<12 weeks
• Karnofsky Performance Status \<70%
• Hepatic impairment (Child-Pugh score \>5) or significant liver disease including active hepatitis or cirrhosis
• Lab values or any sign, symptom, or medical condition that in the opinion of the PI would prevent surgical resection
• Medical or psychiatric conditions that compromise the patient's ability to give informed consent.
• Pregnant or lactating women
• Receiving or planned to receive, during the duration of the study, concomitant medication with a high chance of hepatotoxicity, as judged by the PI based on standard protocols within the study center
• Alcohol consumption within 72 hours before Pegsitacianine administration
• Received an investigational agent within the shorter of 5 half-lives or 30 days before Pegsitacianine dosing
• Inability to adhere to the schedule of assessments or any circumstance that would interfere with the validity of assessments performed in the study
• The PI considers that the patient should not participate in the study
DRUG: Pegsitacianine
Head and Neck Cancer, Unknown Primary Cancer, Head and Neck Squamous Cell Carcinoma, Head and Neck
UT Southwestern
A Study of Teclistamab in Combination With Daratumumab and Lenalidomide (Tec-DR) and Talquetamab in Combination With Daratumumab and Lenalidomide (Tal-DR) in Participants With Newly Diagnosed Multiple Myeloma (MajesTEC-7)
The purpose of this study is to compare the efficacy of teclistamab in combination with daratumumab and lenalidomide (Tec-DR) and talquetamab in combination with daratumumab and lenalidomide (Tal-DR) versus daratumumab, lenalidomide, dexamethasone (DRd).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Aimaz Afrough
ALL
18 Years and over
PHASE3
NCT05552222
STU20250678
Inclusion Criteria:
* Have a diagnosis of multiple myeloma according to the International Myeloma Working Group (IMWG) diagnostic criteria
* Be newly diagnosed and not considered a candidate for high-dose chemotherapy with autologous stem cell transplant (ASCT) due to: ineligible due to advanced age OR; ineligible due to the presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with ASCT OR; deferral of high-dose chemotherapy with ASCT as initial treatment
* Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2
* A participant must agree not to be pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of study treatment
* A participant must agree not to plan to father a child while enrolled in this study or within 100 days after the last dose of study treatment
Exclusion Criteria:
* Received any prior therapy for multiple myeloma or smoldering myeloma other than a short course of corticosteroids (not to exceed total of 160 milligrams \[mg\] dexamethasone or equivalent). In addition, received a cumulative dose of systemic corticosteroids equivalent to greater than or equals to (\>=) 20 mg of dexamethasone within 14 days before randomization
* Had plasmapheresis within 28 days of randomization
* Had a stroke, transient ischemic attack, or seizure within 6 months prior to randomization
* Known allergies, hypersensitivity, or intolerance to teclistamab or talquetamab excipients
* Known contraindications to the use of daratumumab or lenalidomide per local prescribing information
* Myeloma Frailty Index of \>=2 with the exception of participants who have a score of 2 based on age alone DRUG: Teclistamab, DRUG: Daratumumab, DRUG: Lenalidomide, DRUG: Dexamethasone, DRUG: Talquetamab
Multiple Myeloma
UT Southwestern
Study of SGR-1505 in Mature B-Cell Neoplasms
The purpose of this study is to evaluate safety and tolerability and to determine the maximum tolerated dose (MTD) and/or recommended dose (RD) of SGR-1505.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Heather Wolfe
All
18 Years and over
Phase 1
NCT05544019
STU-2023-0636
Inclusion Criteria:
• Subject must have a history of histologically or cytologically confirmed mature B-cell malignancy.
• Subject must have measurable or detectable disease according to the applicable disease-specific classification system.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Life expectancy ≥ 12 weeks.
Exclusion Criteria:
• For a subject with indolent NHL and CLL/SLL, the subject is in need of immediate cytoreductive therapy (unless the patient has no remaining treatment choice with potential benefit) and has an indication for treatment.
• Subject has previous invasive malignancy in the last 2 years.
• Subject has a known allergy to SGR-1505 or excipients of SGR-1505.
• Subject has symptomatic or active CNS involvement of disease.
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that would place the participant at increased risk to the use of an investigational drug.
Drug: SGR-1505
Mature B-Cell Neoplasm, Non Hodgkin Lymphoma, DLBCL, Waldenström Macroglobulinemia, MALT Lymphoma, Follicular Lymphoma, Pediatric-Type Follicular Lymphoma, IRF4 Gene Rearrangement, EBV-Positive DLBCL, Nos, Burkitt Lymphoma, Plasmablastic Lymphoma, High-grade B-cell Lymphoma, Primary Cutaneous Follicle Center Lymphoma, Primary Effusion Lymphoma, Mantle Cell Lymphoma, DLBCL Germinal Center B-Cell Type, Primary Mediastinal Large B Cell Lymphoma, T-Cell/Histiocyte Rich Lymphoma, ALK-Positive Large B-Cell Lymphoma, Primary Cutaneous Diffuse Large B-Cell Lymphoma, Splenic Marginal Zone Lymphoma, Chronic Lymphocytic Leukemia, Nodal Marginal Zone Lymphoma, HHV8-Positive DLBCL, Nos, Lymphoplasmacytic Lymphoma, Duodenal-Type Follicular Lymphoma, Lymphoid Leukemia, Non-Hodgkins Lymphoma
MALT1, NF-kB
UT Southwestern
Study of JANX007 in Subjects With Metastatic Castration-Resistant Prostate Cancer (ENGAGER-PSMA-01)
This study is a first-in-human, Phase 1, open-label, multicenter study to assess the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and the preliminary efficacy of JANX007 in adults with metastatic castration-resistant prostate cancer (mCRPC).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
MALE
18 Years to 100 Years old
PHASE1
NCT05519449
STU-2024-0923
Inclusion Criteria:
* Male ≥18 years of age at the time of signing informed consent
* Histologically or cytologically confirmed adenocarcinoma of the prostate
* For Dose Escalation and Backfill: Having mCRPC that progressed after at least one novel anti-androgen therapy and at least one taxane containing regimen. Participants who have actively refused a taxane containing regimen or are medically unsuitable to receive taxane are eligible
* Adequate organ function
* For Monotherapy Expansion Part a: Have received ≤ 2 anti-androgen therapies in either the HSPC or CRPC setting and no more than 1 prior taxane regimen in the HSPC or CRPC setting. Participants who have actively refused a taxane regimen or are medically unsuitable to receive taxane are eligible.
* For Monotherapy Expansion Part b: Have received ≤ 2 anti-androgen therapies in either the HSPC or CRPC settings
* For Monotherapy Expansion Part d: Have received ≤ 1 anti-androgen therapy and a poly(ADP-ribose) polymerase (PARP) inhibitor for mCRPC and have progressed following treatment with the PARP inhibitor
* For Combination Expansion: Have received ≤ 1 anti-androgen therapy other than darolutamide in the HSPC setting and ≤ 1 taxane in the mCRPC setting. Participants who have actively refused a taxane regimen or are medically unsuitable to receive taxane are eligible.
Exclusion Criteria:
* Prior solid organ transplant
* Prior treatment with PSMA-targeted CAR-T cell therapy or PSMA-CD3, PSMA-CD28 or other CD3 T-cell engaging bispecific antibodies or radioligand therapy
* Clinically significant cardiovascular disease
* For Monotherapy Expansion Part a: Prior receipt of any treatment other than an ARPI or taxane in the mCRPC setting
* For Monotherapy Expansion Part b: Prior receipt of any treatment other than an anti-androgen therapy or prior receipt of a taxane containing regimen or more than 1 prior line of therapy for mCRPC
* For Monotherapy Part d: More than 1 prior line of therapy for mCRPC or prior receipt of any treatment other than an anti-androgen therapy and PARP inhibitor for mCRPC or prior receipt of a taxane in the mCRPC setting
* For Combination expansion: More than 1 prior line of therapy for mCRPC or prior receipt of any treatment other than a taxane for mCRPC or prior receipt of Darolutamide or prior receipt of a taxane for HSPC
* Active clinically significant infection (bacterial, viral, fungal, mycobacteria or other)
* Any medical condition or clinical laboratory abnormality likely to interfere with assessment of safety or efficacy of study treatment BIOLOGICAL: JANX007, DRUG: Darolutamide
Prostate Cancer, Metastatic Castration-resistant Prostate Cancer, Castration Resistant Prostatic Cancer, Prostate
Prostate Cancer, Castration-resistant prostate cancer
UT Southwestern
Molecular and Clinical Risk-Directed Therapy for Infants and Young Children With Newly Diagnosed Medulloblastoma
This is a multi-center, multinational phase 2 trial that aims to explore the use of molecular and clinical risk-directed therapy in treatment of children 0-4.99 years of age with newly diagnosed medulloblastoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Daniel Bowers
ALL
to 59 Months old
PHASE2
NCT05535166
STU-2023-0119
Inclusion Criteria - Screening Phase (All Patients)
* Participants with presumptive/suspected newly diagnosed medulloblastoma.
* Participant meets one of the following criteria at the time of screening:
* Age \< 36 months OR Age ≥ 36 months and \< 60 months with presumptive/suspected non-metastatic disease
* Participant must have adequate tumor tissue from primary tumor for central review of pathology and molecular classification by methylation and IHC
* Participant must be able to begin treatment as outlined in the protocol within 36 days of definitive surgery (day of surgery is Day 0). In case a second surgery is clinically indicated to remove the residual tumor prior to starting treatment, the second surgery will be considered as the definitive surgery (Day 0).
* Parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines.
Exclusion Criteria - Screening Phase
* Participants with other clinically significant medical disorders (i.e., serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction) that could compromise their ability to tolerate protocol therapy or would interfere with the study procedure.
Inclusion Criteria - Study Enrollment (All Patients)
* Participant must be \< 60 months of age at time of enrollment.
* Note: Each treatment stratum has additional specific age requirements
* Participant must have confirmation of newly diagnosed medulloblastoma per Central Review:
* Central review includes histopathology, IHC and St. Jude Clinical Genomic Methylation Profiling conducted on MLPNet. If tissue or the extracted DNA does not meet quality control criteria for methylation analysis or if methylation classifier is unable assign molecular group/subgroup within the assigned classifier (MLPNet) parameters, then IHC will be used to define molecular group of these cases. IHC cannot be used to determine molecular subgroup. Therefore, IHC defined SHH patients will be enrolled on Stratum S-1 under "SHH-NOS", and all NWNS and indeterminate molecular group will be enrolled on stratum N.
* Note: Diagnosis of medulloblastoma, as well as group and subgroup assignment, will be done by central pathology review at St. Jude only. No outside testing is allowed for trial enrollment.
* Participant must have disease staged by MRI of the brain and spine and by cytologic examination of CSF\* and be placed into the following categories:
* M0: no evidence of metastatic disease.
* must include a negative CSF cytology result
* M1: Tumor cells found in the CSF but no other evidence of metastasis
* M2: Intracranial tumor beyond the primary tumor site
* M3: Metastatic disease in the spine
* M4: Extraneural metastatic disease
* \*All participants are to undergo CSF cytologic examination regardless of presence or absence of gross metastatic disease unless procedure is medically contraindicated. CSF is to be obtained by lumbar puncture (LP) performed at least 10 days after surgery. If LP is medically contraindicated, ventricular CSF from a shunt or Ommaya reservoir may be used for staging but this is not the preferred option due to lower sensitivity. If LP is medically contraindicated and the patient doesn't have a shunt or reservoir for CSF sampling, the treating physician should reach out to PI or Co-PI regarding decision on enrollment to SJiMB21. The decision to enroll without CSF cytology will be made on case-by-case basis.
* Note: Participants who have M2 disease and positive CSF will be assigned to M3.
* Note: Participants will be assigned to the highest stage number for which they meet eligibility.
* Note: Treatment stratums may have additional stage requirements.
* Patient must have received no previous radiotherapy, chemotherapy, or other brain tumor-directed therapy other than corticosteroid therapy and surgery.
* Participant must have a Lansky performance score of \> 30 (except for patients with posterior fossa syndrome.
* Participant must have adequate organ function prior to study entry, as defined by:
* Absolute neutrophil counts (ANC) \>750/mm\^3
* Platelet count ≥ 50,000/mm\^3 without support of a platelet transfusion within 7 days
* Hemoglobin ≥8.0 g/dL (with or without support of a blood transfusion).
* Normal liver function as defined by Alanine aminotransferase (ALT) concentration ≤ 3 x 45 U/L and total bilirubin ≤ 3 x 1.0.
* Adequate renal function as defined by a serum creatinine concentration:
* Age - 0 to \<1year; Maximum Serum Creatinine (mg/dl) - Male 0.5; Female 0.5
* Age - 1 to \< 2years; Maximum Serum Creatinine (mg/dl) - Male 0.6; Female 0.6
* Age - 1 to \< 2yearsr; Maximum Serum Creatinine (mg/dl) - Male 0.8; Female 0.8
* Participant's parent or legal guardian has the ability to understand and the willingness to sign a written informed consent document according to institutional guidelines.
Inclusion Criteria - Stratum S-2
* Participant must have confirmed diagnosis of the following medulloblastoma molecular group and subgroup per Central Review.
* Medulloblastoma SHH-2
* Participant must meet one of the following criteria at time of enrollment:
* Age \<36 months OR Age ≥ 36 months and \< 60 months with non-metastatic disease (M0) Inclusion Criteria - Stratum S-1
* Participant must have confirmed diagnosis of one of the following medulloblastoma molecular subgroups per Central Review.
* Medulloblastoma SHH-1
* Medulloblastoma SHH-3
* Medulloblastoma SHH-4
* Medulloblastoma SHH-NOS
* Includes medulloblastoma cases that could not be assigned to a molecular subgroup using the DNA methylation classifier, but which are in the SHH group and/or cases defined as SHH by IHC.
* Participant must be \< 36 months of age at time of enrollment
* Note: Patients who are \< 36 months of age, regardless of metastatic status (M0/M+), are eligible for enrollment on stratum S-1.
Inclusion Criteria - Stratum N
* Participant must have confirmed diagnosis of one of the following medulloblastoma molecular subgroups per Central Review.
* Medulloblastoma G3
* Medulloblastoma G4
* Medulloblastoma - Not classified into SHH (i.e., NWNS or indeterminate)
* Includes medulloblastoma cases that could not be assigned to a molecular group using the DNA methylation classifier but which are in the NWNS class and/or defined as NWNS by IHC.
* Participant must be \<36 months of age at time of enrollment
* All NWNS patients (M+ and M0) are eligible for enrollment in stratum N
Exclusion Criteria - All Patients
* CNS embryonal tumor other than medulloblastoma, for example, patients with diagnosis of Atypical Teratoid/Rhabdoid Tumor (ATRT), PNET, Pineoblastoma, Ependymoma, and ETMR are excluded.
* Participant with prior treatment for medulloblastoma, including:
* Radiotherapy
* Chemotherapy
* Cancer directed immunotherapy
* Targeted agents
* NOTE: Corticosteroid therapy is acceptable; prior treatment with chemotherapy, immunotherapy or targeted agents for non-cancer directed indications are acceptable as long as these have been stopped at least 14 days prior to start of therapy or 2 half-lives from last dose. (i.e., methotrexate for juvenile rheumatoid arthritis, JAK inhibitor therapy for eczema, etc.)
* Participant who is actively receiving any other investigational agents.
* Participant with other clinically significant medical disorders (i.e., serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction) that could compromise their ability to tolerate protocol therapy or would interfere with the study procedures or results.
PROCEDURE: Surgical resection, PROCEDURE: Ommaya/VPS, DRUG: Methotrexate, DRUG: Cisplatin, DRUG: Vincristine, DRUG: Cyclophosphamide, DRUG: Carboplatin, DRUG: Topotecan, DRUG: Etoposide, DRUG: Pegfilgrastim, DRUG: Filgrastim, RADIATION: Irradiation, OTHER: Educational and Media Intervention, OTHER: SOC, Educational and Media Intervention, DRUG: Methotrexate
Medulloblastoma, Brain and Nervous System
SJiMB21, Brain Cancer, Brain Tumors in Children, Medulloblastoma Sonic Hedgehog subgroup 1, Medulloblastoma Sonic Hedgehog subgroup 2, Medulloblastoma Sonic Hedgehog subgroup 3, Medulloblastoma Sonic Hedgehog subgroup 4, Medulloblastoma Sonic Hedgehog-not otherwise specified, Medulloblastoma G3, Medulloblastoma G4, Medulloblastoma indeterminate, MLPNet, Neural Net Classification Pipeline, Non-WNT non-SHH medulloblastoma, Posterior fossa syndrome, St. Jude Brain Tumor Studies, Treatment for Brain Tumors in Infants and Young Children, Untreated Childhood Medulloblastoma
Children’s Health
A Study to Give Treatment Inside the Eye to Treat Retinoblastoma
This phase II trial tests the safety and side effects of adding melphalan (by injecting it into the eye) to standard chemotherapy in early treatment of patients with retinoblastoma (RB). RB is a type of cancer that forms in the tissues of the retina (the light-sensitive layers of nerve tissue at the back of the eye). It may be hereditary or nonhereditary (sporadic). RB is considered harder to treat (higher risk) when there are vitreous seeds present. Vitreous seeds are RB tumors in the jelly-like fluid of the eye (called the vitreous humor). The term, risk, refers to the chance of the cancer not responding to treatment or coming back after treatment. Melphalan is in a class of medications called alkylating agents. It may kill cancer cells by damaging their deoxyribonucleic acid (DNA) and stopping them from dividing. Other chemotherapy drugs given during this trial include carboplatin, vincristine, and etoposide. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Adding melphalan to standard chemotherapy early in treatment may improve the ability to treat vitreous seeds and may be better than standard chemotherapy alone in treating retinoblastoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Daniel Bowers
ALL
up to 18 Years old
PHASE2
NCT05504291
STU-2023-0581
Inclusion Criteria:
* Patient must be \< 18 years of age at enrollment
* Patient must have newly diagnosed intraocular (localized) retinoblastoma and meet one of the following criteria:
* Unilateral Group D retinoblastoma with vitreous seeding; OR
* Bilateral retinoblastoma with worst eye Group D, with vitreous seeding present and the contralateral eye is Group A-C; OR
* Bilateral Group D retinoblastoma with at least one eye with vitreous seeding; OR
* Bilateral retinoblastoma with one Group D eye with vitreous seeding and one Group E eye where the Group E eye has been enucleated prior to any therapy. Note exclusion for high-risk features
* Bilateral retinoblastoma with one Group D eye with vitreous seeding and one Group E eye where the Group E eye has not been enucleated prior to any therapy at the discretion of the treating physician. Note exclusion for patients with evidence of metastatic or extra orbital spread
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\<16 years of age
* Peripheral absolute neutrophil count (ANC) \>= 750/uL (must be performed within 7 days prior to enrollment unless otherwise indicated)
* Platelet count \>= 75,000/uL (transfusion independent) (must be performed within 7 days prior to enrollment)
* A serum creatinine based on age/sex as follows (must be performed within 7 days prior to enrollment; must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment):
* 1 month to \< 6 months = 0.4 (male and female)
* 6 months to \< 1 year = 0.5 (male and female)
* 1 to \< 2 years = 0.6 (male and female)
* 2 to \< 6 years = 0.8 (male and female)
* 6 to \< 10 years = 1.0 (male and female)
* 10 to \< 13 years = 1.2 (male and female)
* 13 to \< 16 years = 1.5 (male) and 1.4 (female)
* \>= 16 years = 1.7 (male) and 1.4 (female) OR - a 24-hour urine Creatinine clearance \>= 70 mL/min/1.73 m\^2 OR - a glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
* Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
* For patients \< 1 month of age, serum creatinine levels must be \< 1.5 x the treating institution's creatinine upper limit of normal (ULN) for patients \< 1 month of age or the creatinine clearance or radioisotope GFR must be \>= 70 mL/min/1.73 m\^2
* The threshold creatinine values were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Center for Disease Control (CDC)
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment; must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment)
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (must be performed within 7 days prior to enrollment; must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment)
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
Exclusion Criteria:
* Patients with evidence of metastatic or extra-orbital spread
* Patients must not have an invasive infection at time of protocol entry
* Patients must not have had any prior anti-cancer therapy other than cryotherapy and/or laser therapy (green or infrared) to the study eye(s) and non-study eye, including systemic chemotherapy, intra-arterial chemotherapy, radioactive plaque, brachytherapy, or radiation therapy.
* Note: A study eye is defined as being Group D with vitreous seeding. Patients may have had enucleation of one eye as long as the remaining eye is Group D with vitreous seeds
* Patients with bilateral disease who undergo enucleation of a Group E eye prior to initiation of therapy and show evidence of high-risk histopathology features in the enucleated eye. High-risk histopathology includes choroid involvement \>= 3 mm, post lamina optic nerve involvement, full thickness scleral invasion or optic nerve invasion to the cut end
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, DRUG: Etoposide, PROCEDURE: Examination Under Anesthesia, PROCEDURE: Magnetic Resonance Imaging, DRUG: Melphalan, PROCEDURE: Ultrasound Biomicroscopy, DRUG: Vincristine
Bilateral Retinoblastoma, Childhood Intraocular Retinoblastoma, Group D Retinoblastoma, Stage I Retinoblastoma, Unilateral Retinoblastoma, Eye and Orbit
Children’s Health
Study of Cabozantinib and Nivolumab in Metastatic Castration Resistant Prostate Cancer (CANOPY)
This is a multicenter, single-arm, two-stage open-label phase 2 study of the combination of cabozantinib + nivolumab in subjects with advanced castration-resistant prostate cancer (CRPC).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Qian Qin
MALE
18 Years and over
PHASE2
NCT05502315
STU-2023-0313
Inclusion Criteria:
Subjects must meet all of the following applicable inclusion criteria to participate in this study:
* Willing and able to provide, or have a legally authorized representative provide, written informed consent and HIPAA authorization for the release of personal health information. A signed informed consent must be obtained before screening procedures are performed. NOTE: HIPAA authorization may be either included in the informed consent or obtained separately.
* Males 18 years of age and above.
* Histological or cytological proof of prostate adenocarcinoma or mixed adenocarcinoma/neuroendocrine tumors. Pure small cell of the prostate is not allowed.
* ECOG status of ≤ 2
* Progressive mCRPC as defined: 1) castrate levels of serum testosterone \< 50 ng/dL AND 2) progressive disease as defined by PSA or radiographic progression. Subjects with measurable and non-measurable disease (i.e., bone only metastases) are allowed. NOTE: ENROLLMENT of subjects with non-measurable disease (i.e., bone only metastases) will be capped at 50% of enrollment target (n=25).
* Must have exposure to one prior taxane (or be taxane ineligible or refuse taxane) AND one prior AR-targeting agent (for example, abiraterone, enzalutamide, apalutamide, darolutamide). Receipt of taxane or AR-targeting agent may be in the hormone sensitive or castration resistant setting. Subjects may have received more than 1 prior Androgen receptor signaling inhibitors (ARSI). Subjects may have had prior 177Lu-PSMA-617.
* Recovery to baseline or ≤ Grade 1 CTCAE v5.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
* Normal organ function with acceptable initial laboratory values within 14 days of treatment start:
* WBC: ≥ 2,500/mcL
* ANC: ≥ 1,500/mcL
* Hemoglobin: ≥ 9 g/dL (transfusions are permitted)
* Platelet count: ≥ 100,000/mcL
* Serum creatinine or calculated Creatinine Clearance: Serum creatinine ≤ 1.5 x ULN or calculated CrCl ≥ 30 mL/min as defined by Cockcroft-Gault equation
* Total Bilirubin: ≤ 1.5 x ULN (≤ 3 x ULN for subjects with documented Gilbert's disease)
* SGOT (AST): ≤ 3 x ULN
* SGPT (ALT): ≤ 3 x ULN
* Alkaline Phosphatase (ALP): ≤ 5 x ULN with documented bone metastases
* Serum Albumin: ≥ 2.8 g/dL
* Urine protein/creatinine ratio (UPCR): ≤ 2 mg/mg (≤ 113.2 mg/mmol), or 24-h urine protein ≤ 2 g
* Subjects must agree to use a medically acceptable method of birth control as outlined in the protocol
* HIV-positive with negative viral loads on stable antiretroviral regimen will be considered eligible. Subjects must have CD4 count \> 350.
Exclusion Criteria:
Subjects meeting any of the criteria below may not participate in the study:
* Disease progression on prior checkpoint inhibitor treatment.
* Prior cabozantinib.
* Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
* Receipt of any type of cytotoxic, biologic or investigational systemic anti-cancer agent within 4 weeks before first dose of study treatment.
* Treatment with abiraterone, apalutamide, or darolutamide within 2 weeks of treatment initiation. Treatment with investigational prostate cancer directed therapy within 4 weeks of treatment initiation. Treatment with enzalutamide within 4 weeks of treatment initiation.
* Receipt of more than 1 line of chemotherapy (including both hormone sensitive and CRPC). First-generation anti-androgen use (such as bicalutamide) will not be tabulated as a line of therapy.
* Administration of a live, attenuated vaccine within 30 days prior to first dose of study treatment.
* Active autoimmune disease or condition requiring prednisone \>10 mg daily (or equivalent). Physiologic replacement is permitted. Topical, ocular, intra-articular steroids or inhaled corticosteroids are permitted.
* Imminent or established spinal cord compression based on clinical and/or imaging findings.
* Radiation therapy within 1 week of study treatment start.
* Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment.
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
* Malabsorption syndrome.
* Requirement for hemodialysis or peritoneal dialysis.
* History of solid organ or allogenic stem cell transplant.
* Active hepatitis B/C or positive TB test with active mycobacterial infection requiring systemic treatment.
* Active treatment (within 5 days of registration) with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:
* Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose molecular weight heparins (LMWH).
* Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
* The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
* Cardiovascular disorders:
* Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
* Uncontrolled hypertension defined as sustained blood pressure (BP) \> 150 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment.
* Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose of study treatment.
* Subjects with a diagnosis of incidental, subsegmental PE or DVT within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation (see exclusion criterion above) for at least 1 week before first dose of study treatment.
* Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation
* The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.
* Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment.
* Clinically significant hematuria, hematemesis, or hemoptysis of \> 0.5 teaspoon (2.5ml) of red blood, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 12 weeks before first dose of study treatment.
* Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
* Lesions invading or encasing any major blood vessels.
* Other clinically significant disorders that would preclude safe study participation.
* Serious non-healing wound/ulcer/bone fracture.
* Uncompensated/symptomatic hypothyroidism.
* Moderate to severe hepatic impairment (Child-Pugh B or C).
* Major surgery (e.g., laparoscopic nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 2 weeks before first dose of study treatment. Minor surgeries within 10 days before first dose of study treatment. Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
* Corrected QT interval calculated by Fridericia formula (QTcF) \>500 ms per electrocardiogram (ECG) within 14 days before first dose of study treatment \[add reference for Fridericia formula\]. NOTE: If a single ECG shows a QTcF with an absolute \>500 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility.
* Any other active malignancy at time of first dose of study treatment or diagnosis of another malignancy within 3 years prior to first dose of study treatment that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer or superficial bladder cancer.
* Known allergy to any of the compounds under investigation.
* Inability to swallow tablets. DRUG: Cabozantinib, DRUG: Nivolumab
Castration-Resistant Prostate Cancer, Metastatic Cancer, Prostate
Castration resistant prostate cancer, Immunotherapy, Targeted therapy, Bone metastases
UT Southwestern
A Study of LP-300 With Carboplatin and Pemetrexed in Never Smokers With Advanced Lung Adenocarcinoma (HARMONIC)
The goal of this clinical trial is to determine clinical advantages for LP-300 in combination with carboplatin and pemetrexed in the never smoker patient population. The primary objectives of this study are to determine progression-free survival (PFS) and overall survival (OS) in the study-defined patient population when LP-300 is co-administered with the standard of care chemotherapy drugs carboplatin and pemetrexed compared to carboplatin and pemetrexed alone. This has been designed as a multicenter, open label, phase II trial with 90 patients to be enrolled in the United States.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Jonathan Dowell
ALL
18 Years and over
PHASE2
NCT05456256
STU-2023-0857
Inclusion Criteria:
• Patients with confirmed histopathological diagnosis of inoperable advanced (Stage III or IV) primary adenocarcinoma (including bronchioalveolar cell carcinoma) of the lung with specific actionable genomic alterations (e.g., mesenchymal epithelial transition (MET) exon14 skipping mutations, anaplastic lymphoma kinase (ALK), epidermal growth factor receptor (EGFR), neurotrophic tyrosine receptor kinase (NTRK) fusions, etc.). If pathological or radiological findings are inconclusive for a diagnosis of primary adenocarcinoma of the lung, additional studies must be performed to confirm primary lung versus metastatic adenocarcinoma. Patients with no known actionable genomic alterations are ineligible to enroll in the study.
• Locally advanced inoperable or metastatic lung cancer.
• Patients must be never smokers: a never smoker is an adult who has never smoked, or who has smoked less than 100 cigarettes (or equivalent in other products such as vapes, cigars, pipes, hookahs, and marijuana use) in his or her lifetime. Note: a patient with actionable genomic alteration(s) who is a former smoker may be enrolled if such a patient would ordinarily be treated with pemetrexed and carboplatin combination based on institutional standard clinical practice; consultation with the sponsor's Medical monitor would be required
• Patients who have received systemic treatment with tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer but have experienced disease progression, unacceptable TKI-related toxicities, or are unable to tolerate the further use of TKIs.
• Prior radiation therapy is allowed, provided (1) that at least one area of measurable tumor (by computed tomography (CT) scan with at least one target lesion) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 that has not been subject to prior irradiation, and (2) that any such therapy is completed and any radiation-induced sequelae are recovered at least 21 days before randomization.
• Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Patients who are at least 18 years of age.
• Patients with documented stable central nervous system (CNS) metastases with no cognitive deficits, or progressive sensory or motor deficits, or seizures during the last 21 days prior to enrollment are eligible. Patients must have discontinued anti-seizure medications and steroids at least 14 days prior to patient enrollment.
• Patients must have fully recovered from any prior major surgical or diagnostic staging procedure (e.g., thoracotomy, mediastinoscopy), and have a post-operative status of at least 30 days before enrollment.
• Patients must have adequate bone marrow, adequate hepatic function, and baseline creatinine levels documented by specific laboratory criteria within 21 days prior to enrollment, including the following: * White blood cell count ≥ 2 x 10\*9/L * Absolute neutrophil count (ANC) ≥ 1.5 x 10\*9/L * Hemoglobin ≥ 10 g/dL * Platelet count ≥ 100 x 10\*9/L * Total bilirubin \< 1.5 x the upper limit of normal (ULN). For patients with Gilbert's syndrome, total bilirubin \< 2.5 x ULN * Aspartate aminotransferase/ serum glutamic oxaloacetic transaminase (AST/SGOT) ≤ 2.5 x ULN * Alanine aminotransferase/ serum glutamic pyruvic transaminase (ALT/SGPT) ≤ 2.5 x ULN * Alkaline phosphatase ≤ 2.5 x ULN * Baseline serum creatinine level no greater than 1.5 mg/dL or 133 μmol/L. * Creatinine clearance ≥ 45 mL/min as calculated using the Cockcroft-Gault methodology (Cockcroft 1976) * Magnesium ≥ 1.7 mg/dL
• Female patients of child-bearing potential must have a negative pregnancy test and must agree to use an acceptable contraceptive method during the study and for 12 weeks after their last dose of study treatment. Male patients with partners of child-bearing potential must also agree to use an adequate method of contraception for the duration of the study and for 12 weeks after their last dose of study treatment. Note: a) A patient is considered of childbearing potential if she is biologically capable of having children and is sexually active. Medically acceptable contraceptives include: (1) surgical sterilization (such as a tubal ligation, hysterectomy, or vasectomy), (2) approved hormonal contraceptives (such as birth control pills, patches, implants or injections), (3) barrier methods (such as a condom or diaphragm) used with a spermicide (only if used in combination with another mentioned method), or (4) an intrauterine device (IUD). Contraceptive measures and other medications sold for emergency use after unprotected sex, are not acceptable methods for routine use. If a female patient becomes pregnant, study therapy must be discontinued immediately. Lastly, b) the period for use of contraception after last dose of pemetrexed or carboplatin should be determined by the domestic drug labels and/or institutional standard clinical practice. For S Korea, contraception is to be used for 6 months after the last dose.
• Patients must have been disease-free at least two years for other malignancies, excluding: * Curatively-treated basal cell carcinoma, * Ductal carcinoma in situ (DCIS) of the breast * Non-melanomatous carcinoma of the skin, or * Carcinoma in situ of the cervix.
• Be willing to provide an archival tumor tissue sample, if available. The archival sample must be from a tumor lesion that was not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. The sample must have been obtained less than 36 months prior to consent.
• Provide signed, written, Institutional Review Board (IRB) approved informed consent prior to any screening procedures.
Exclusion Criteria:
• Patients with small cell, squamous cell, large cell, undifferentiated, mesothelioma, or any form of mixed (e.g., small cell and adenocarcinoma or squamous and adenocarcinoma) histopathological diagnosis of primary lung cancer.
• Patients with metastatic adenocarcinoma arising from any primary site other than the lung.
• Patients who have received any prior investigational agents except for investigational TKI drugs. The minimum drug washout period for all TKIs, including approved and investigational, is ≥ 5 half-lives or 2 weeks, whichever is shorter.
• Patients who have received chemotherapy and/or immunotherapy but transitioned to a TKI with no evidence of disease progression will be allowed to enroll. Patients who experienced disease progression while on chemotherapy and/or immunotherapy will be ineligible for the trial.
• Patients taking medications that are sensitive substrates of CYP2C19 or P-gp transporters
• Patients with recent onset (within 6 months of randomization) of congestive heart failure (New York Heart Association Classification Class II or greater), angina pectoris, unstable angina pectoris, serious uncontrolled cardiac arrhythmias, myocardial infarction, stroke, or transient ischemic attacks.
• Have a corrected QT interval (using Fridericia's correction formula) (QTcF) of \> 470 msec. (average of triplicate ECGs) at Screening and/or on C1D1 (pre- dose) except for a documented bundle branch block or unless secondary to pacemaker. In the case of a documented bundle branch block or a pacemaker, discussion with the Medical Monitor is required prior to enrollment.
• Patients with unstable CNS metastases (characterized by progressive sensory/motor impairment, cognitive/speech impairment, or seizure activity) within 21 days before enrollment.
• Patients who do not have at least one (1) measurable disease site that has not been previously irradiated.
• Patients who are known to be positive for human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HbsAg) or hepatitis C virus (HCV).
• Patients with active infections, active interstitial lung disease, uncontrolled high blood pressure, uncontrolled diabetes mellitus, uncontrolled seizures (not due to CNS metastases) within the last 3 months, or other serious underlying medical condition.
• Patients with documented hypersensitivity to any of the study medications (LP-300, pemetrexed, carboplatin and/or excipients) or supportive agents that may be used.
• Patients who are pregnant or are breastfeeding.
• Patients who have undergone blood transfusions within 10 days before randomization.
• Any other medical intervention or other condition which, in the opinion of the Principal Investigator, could compromise adherence to study requirements or confound the interpretation of study results.
• Patients who have a life expectancy of less than 3 months.
DRUG: LP-300, DRUG: Pemetrexed, DRUG: Carboplatin
Adenocarcinoma of Lung, Carcinoma, Non-Small-Cell Lung, Lung/Thoracic
never smoker, non smoker, EGFR, ALK, ROS, MET, tyrosine kinase inhibitor, TKI, pemetrexed, carboplatin, NSCLC, never-smoker, non-smoker, TK inhibitor, lung cancer
UT Southwestern; Parkland Health & Hospital System
A Study of TTI-101 as Monotherapy and in Combination in Participants With Locally Advanced or Metastatic, and Unresectable Hepatocellular Carcinoma
The primary objectives of Cohort A Phase 1b are to evaluate the safety and tolerability of TTI-101 orally administered as a single agent to participants with locally advanced or metastatic, and unresectable Hepatocellular Carcinoma (HCC) and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of TTI-101 as a single agent. The primary objectives of Cohort A Phase 2 are to evaluate the safety and tolerability of TTI-101 orally administered as a single agent at the RP2D to participants with locally advanced or metastatic, and unresectable HCC and to assess the preliminary efficacy of TTI-101 as a single agent in participants with locally advanced or metastatic, and unresectable HCC. The secondary objectives of Cohort A Phase 2 are to assess response, progression, survival, and pharmacokinetics. The primary objectives of Cohorts B and C Phase 1b are to evaluate the safety and tolerability of TTI-101 orally administered in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C) to participants with locally advanced or metastatic, or unresectable HCC and to determine the MTD and/or RP2D of TTI-101 when used in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C). The primary objectives of Cohorts B and C Phase 2 are to evaluate the safety and tolerability of TTI-101 orally administered in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C) at the RP2D to participants with locally advanced or metastatic, and unresectable HCC and to assess the preliminary efficacy of TTI-101 in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C) to participants with locally advanced or metastatic, and unresectable HCC. The secondary objectives of Cohorts B and C Phase 2 are to assess response, progression, survival, and pharmacokinetics.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Hsieh
All
18 Years and over
Phase 1/Phase 2
NCT05440708
STU-2022-0622
Inclusion Criteria:
• Able to understand and willing to provide informed consent and able to comply with the study procedures and restrictions.
• Age ≥18 years at the time of informed consent.
• Have histologically or radiographically (Liver Imaging Reporting and Data Systems category 5) confirmed diagnosis of locally advanced or metastatic, and unresectable HCC. Participants without cirrhosis require histological confirmation.
• Cohorts A and B only: Willing to provide a representative fresh tumor tissue specimen prior to enrollment. The fresh tumor specimen must be obtained after progression on the prior therapy. No biopsy is required for participants in Cohort C.
• Measurable disease as per RECIST Version 1.1. Participants who received prior local therapy are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST Version 1.1.
• Able to swallow tablets.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Has adequate hematologic and organ function as defined by the following local laboratory values at screening:
• Absolute neutrophil count (ANC) ≥1.5 × 10^9/L (1500/μL) without granulocyte colony-stimulating factor support.
• Lymphocyte count ≥0.5 × 10^9/L (500/μL).
• Platelet count ≥75 × 10^9/L (75,000/μL) without transfusion.
• Hemoglobin ≥90 g/L (9 g/dL). Participants may be transfused to meet this criterion.
• Serum albumin ≥28 g/L (2.8 g/dL).
• AST, ALT, and alkaline phosphatase (ALP) ≤5 × upper limit of normal (ULN).
• Serum bilirubin ≤2 mg/dL.
• Adequate renal function defined as either:
• creatinine clearance ≥40 mL/min calculated using the Cockcroft-Gault formula, or
• 24-hour urine collection.
• Prothrombin time/international normalized ratio (PT/INR) and activated partial thromboplastin time (aPTT) ≤2 × ULN, except for participants receiving anticoagulation therapy.
• Child-Pugh class A or B7 within 7 days prior to enrollment.
• Females of childbearing potential (ie, ovulating, premenopausal, and not surgically sterile) must:
• Have a negative serum pregnancy test at screening.
• Not be breastfeeding or lactating.
• Agree to use a highly effective method of birth control for the duration of the study and for at least 30 days after the last dose in the study. Effective forms of birth control include barrier methods used in conjunction with a spermicidal agent (according to standard local practices), nonhormonal intrauterine devices, or permanent sterilization.
• Males must:
• Agree to use a condom for at least 30 days after the last dose in the study even if vasectomized in order to prevent delivery of the drug via seminal fluid.
• Agree to abstain from sperm donation through 30 days after administration of the last dose of the study treatment.
• Unless surgically sterile, males with female partners of childbearing potential must agree to use 2 methods of acceptable birth control for at least 30 days after the last dose in the study. Effective forms of birth control include barrier methods used in conjunction with a spermicidal agent (according to standard local practices), nonhormonal intrauterine devices in female partners, or permanent sterilization. Cohort A:
• In addition to the general inclusion criteria, participants enrolled in Cohort A must have demonstrated objective progression on up to 3 prior lines of systemic antitumor drug therapy. Cohort B:
• In addition to the general inclusion criteria, participants enrolled in Cohort B must have demonstrated objective progression following at least 2 cycles of first-line anti-PD-1 or anti-PD-L1 monotherapy or combination therapy. Participants may have received no more than one line of prior therapy.
• Agree to use contraception as specified in the general inclusion criteria for at least 4 months following the last dose of pembrolizumab in accordance with the approved prescribing information. Cohort C:
• In addition to the general inclusion criteria, participants enrolled in Cohort C must be naïve to systemic treatment for locally advanced or metastatic, and unresectable HCC.
• Must have had an evaluation (gastroduodenoscopy) for the presence of varices within 6 months prior to initiation of bevacizumab therapy.
• Agree to use contraception as specified in the general inclusion criteria for at least 5 months after the last dose of atezolizumab and at least 6 months after the last dose of bevacizumab in accordance with the approved prescribing information.
Exclusion Criteria:
• Pregnant or breastfeeding.
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
• History of leptomeningeal disease.
• Previous treatment of the current malignancy with a signal transducer and activator of transcription (STAT) inhibitor.
• Previous therapy with:
• Standard therapy including chemotherapy, immunotherapy, biologic therapy, or any other anticancer therapy within 28 days (or 5 elimination half-lives for non-cytotoxics, whichever is shorter) of Cycle 1 Day 1 (6 weeks for nitrosoureas or mitomycin).
• Any investigational agent within 28 days (or 5 elimination half-lives for a non-cytotoxic investigational therapy, whichever is shorter) of Cycle 1 Day 1 or 5 half-lives for a small molecule/targeted therapy.
• Extensive prior radiotherapy to more than 30% of bone marrow reserves, or prior bone marrow/stem cell transplantation within 5 years from enrollment.
• Herbal preparations are not allowed throughout the study. These herbal medications include but are not limited to St. John's wort, kava, ephedra (mahung), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng. Participants should stop using herbal medications 7 days prior to the first dose of study treatment.
• Is not fully recovered from all coronavirus disease 2019 (COVID-19)-related symptoms for 2 weeks prior to Cycle 1 Day 1, if previously tested positive for COVID-19.
• Ongoing toxicity (except alopecia) due to a prior therapy, unless returned to baseline or Grade 1 or less.
• Has had major surgery within 3 weeks prior to starting investigational product (IP) or has not recovered from major side effects due to surgery.
• Significantly impaired cardiac function such as unstable angina pectoris, congestive heart failure with New York Heart Association Class III or IV, myocardial infarction within the last 12 months prior to study entry; serious arrhythmia (including QTc prolongation of >470 ms and/or pacemaker) or prior diagnosis of congenital long QT syndrome or left ventricular ejection fraction <50% on screening echocardiogram.
• Pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Participants with indwelling catheters for control of effusions or ascites are allowed.
• History of cerebrovascular accident or stroke within the previous 2 years.
• History of hepatic encephalopathy.
• Uncontrolled or symptomatic hypercalcemia (ionized calcium >1.5 mmol/L, calcium >12 mg/dL, or corrected serum calcium >ULN).
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
• History of Grade 3 or 4 allergic reactions attributed to compounds of similar chemical or biologic composition as TTI-101 (hydroxyl-naphthalene sulfonamides).
• Known active metastases in the central nervous system (unless stable by brain imaging studies for at least 1 month without evidence of cerebral edema and no requirements for corticosteroids or anticonvulsants).
• History of difficulty swallowing oral medications, malabsorption, or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the IP.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Participants with chronic hepatitis B virus (HBV) infection, unless screening viral load <500 IU/mL on stable doses of antiviral therapy. Note: Participants with chronic hepatitis C virus (HCV) infection are allowed to enroll into the study but do not have a defined maximum viral load requirement for study entry. Participants with both HBV and HCV infection are excluded unless they have negative HCV ribonucleic acid (RNA).
• History of malignancy other than HCC within 3 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (eg, 5-year overall survival [OS] rate >90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
• Has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate participation in the clinical study, or compromise compliance with the protocol such as:
• Chronic pancreatitis.
• Active untreated or uncontrolled fungal, bacterial, or viral infections (including COVID-19), sepsis, etc.
• Acute and chronic, active infectious disorders including viral and nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy.
• Is unable to understand and to comply with study instructions and requirements. Cohort B: In addition to the general exclusion criteria, participants enrolled in Cohort B must fulfill the following additional exclusion criteria:
• Discontinued prior treatment with anti-PD-1 or anti-PD-L1 for any reason other than disease progression. Cohort C: In addition to the general exclusion criteria and Cohort B criteria, participants enrolled in Cohort C must fulfill the following additional exclusion criteria:
• Inadequately controlled arterial hypertension (defined as systolic blood pressure [BP] ≥150 mmHg and/or diastolic BP ≥100 mmHg), based on an average of ≥3 BP readings on ≥2 sessions.
• Participant has received prior systemic chemotherapy for locally advanced or metastatic and/or unresectable HCC. However, participant may have received either neo-adjuvant or adjuvant chemotherapy as long as it was completed at least 6 months prior to the first dose of study treatment.
• Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high risk for bleeding and a prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment.
• Urine dipstick for proteinuria ≥2+ at screening. If a 24-hour urine collection shows <1 g of protein in 24 hours, the participant is eligible.
• Current or recent (within 10 days of first dose of study treatment) use of aspirin (>325 mg/day) or treatment with dipyridamole, ticlopidine, clopidogrel, and cilostazol.
• Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants. Prophylactic anticoagulants (eg, low-dose warfarin with target INR <1.5 × ULN or low-dose low molecular weight heparin) are allowed.
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 3 days prior to the first dose of bevacizumab.
• History of gastrointestinal perforation or evidence of abdominal free air not explained by paracentesis or recent surgical procedure.
• Metastatic disease that involves major airways or blood vessels. Participants with portal or hepatic vein involvement are not excluded.
• Participant has experienced any of the following within 6 months prior to enrollment: arterial thromboembolic event (including myocardial infarction, coronary arterial disease, transient ischemic attack, stroke, etc), congestive heart failure, hemoptysis, or pulmonary embolism.
• Participant has experienced a fistula. Cohorts B and C: In addition to the general exclusion criteria and the cohort-specific criteria listed above, participants enrolled in Cohorts B and C must fulfill the following additional exclusion criteria:
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during pembrolizumab treatment or within 5 months after the last dose of pembrolizumab treatment.
• Active or history of immune-mediated disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
• Participants with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
• Participants with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Participants with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (eg, participants with psoriatic arthritis are excluded) are eligible for the study provided all of the following conditions are met:
• Rash must cover <10% of body surface area.
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids.
• No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor α [TNF-α] agents) within 2 weeks prior to initiation of study treatment. Participants receiving low-dose corticosteroids (equivalent of prednisone 10 mg/day or lower) or who receive pulse corticosteroids due to intravenous (IV) contrast allergy are not excluded.
• Active tuberculosis.
• Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Participants receiving prophylactic antibiotics (eg, to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
• Prior allogeneic stem cell or solid organ transplantation.
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
Drug: TTI-101, Drug: Pembrolizumab, Drug: Atezolizumab, Drug: Bevacizumab
Hepatocellular Carcinoma, Liver
Hepatocellular carcinoma, TTI-101, Pembrolizumab, Atezolizumab, Bevacizumab, revert
UT Southwestern; Parkland Health & Hospital System
A Study of ASP2138 Given by Itself or Given With Other Cancer Treatments in Adults With Stomach Cancer, Gastroesophageal Junction Cancer, or Pancreatic Cancer
Claudin 18.2 protein, or CLDN18.2 is a protein found on cells in the digestive system. It is also found on some tumors. Researchers are looking at ways to attack CLDN18.2 to help control tumors. ASP2138 is thought to bind to CLDN18.2 and a protein on a type of immune cell called a T-cell. This "tells" the immune system to attack the tumor. ASP2138 is a potential treatment for people with stomach cancer, gastroesophageal junction cancer (GEJ cancer) or pancreatic cancer. GEJ is where the tube that carries food (esophagus) joins the stomach. Before ASP2138 is available as a treatment, the researchers need to understand how it is processed by and acts upon the body. In this study, ASP2138 will either be given by itself, or given together with standard treatments for gastric, GEJ and pancreatic cancer. Pembrolizumab and mFOLFOX6, and ramucirumab and paclitaxel are standard treatments for gastric and GEJ cancer. mFOLFIRINOX is a standard treatment for pancreatic cancer. This information will help find a suitable dose of ASP2138 given by itself and together with the standard cancer treatments and to check for potential medical problems from the treatments. The main aims of the study are: * To check the safety of ASP2138 and how well people can tolerate medical problems during the study. * To find a suitable dose of ASP2138 to be used later in the study. * These are done for ASP2138 given by itself and when given together with the standard cancer treatments. Adults 18 years or older with stomach cancer, GEJ cancer, or pancreatic cancer can take part. Their cancer is locally advanced unresectable or metastatic. Locally advanced means the cancer has spread to nearby tissue. Unresectable means the cancer cannot be removed by surgery. Metastatic means the cancer has spread to other parts of the body. There should also be the CLDN18.2 marker in a tumor sample. People cannot take part if they need to take medicines to suppress their immune system, have blockages or bleeding in their gut, have specific uncontrollable cancers, have specific infections, have a condition such as hemophagocytic lymphohistiocytosis (HLH) which is when the body over-reacts to a "trigger" such as infection, or have a specific heart condition ("New York Heart Association Class III or IV"). Phase 1: Lower to higher doses of ASP2138 * ASP2138 is either given through a vein (intravenous infusion) or just under the skin (subcutaneous injection). * Different small groups are given lower to higher doses of ASAP2138. * ASP2138 is either given by itself, or given with 1 of 3 standard treatments: * Pembrolizumab and mFOLFOX6 (first treatment for gastric GEJ cancer) * Ramacirumab and paclitaxel (Second treatment for gastric or GEJ cancer) * ASP2138 with mFOLFIRINOX (first treatment for pancreatic cancer) Phase 1b: doses of ASP2138 worked out from Phase 1 * ASP2138 is either given through a vein or just under the skin. This depends on the findings from Phase 1. * People with gastric cancer, GEJ cancer or pancreatic cancer are given doses of ASP2138, worked out from Phase 1. * This includes doses of ASP2138 given by itself and ASP2138 given with the standard cancer treatments. * The standard cancer treatments given depends on the type of cancer they have. End of treatment visit: This is 7 days after final dose of study treatment or if the study doctor decides to stop the person's treatment. People who have locally advanced unresectable pancreatic cancer will not receive ASP2138 by itself.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Syed Kazmi
ALL
18 Years and over
PHASE1
NCT05365581
STU-2022-0586
Inclusion Criteria:
* Participant is considered an adult according to local regulation at the time of signing the informed consent form (ICF).
* Female participant is not pregnant, confirmed by serum pregnancy test \&vmedical evaluation by interview \& at least 1 of the following conditions apply:
* Not a woman of childbearing potential (WOCBP)
* WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 6 months after final study intervention administration.
* Female participant must agree not to breastfeed starting at screening \& throughout the study period \& for 6 months after the final study intervention administration.
* Female participant must not donate ova starting at screening \& throughout the study period \& for 6 months after the final study intervention administration.
* Male participant with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period \& for 6 months after the final study intervention administration.
* Male participant must not donate sperm during the treatment period \& for 6 months after the final study intervention administration.
* Male participant with pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period \& for 6 months after the final study intervention administration.
* Participant's tumor sample is positive for claudin (CLDN)18.2 expression by central immunohistochemistry (IHC) testing.
* Participant has radiographically-confirmed, locally advanced, unresectable or metastatic disease within 28 days prior to the first dose of study intervention.
* Participant has at least 1 measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 within 28 days prior to the first dose of study intervention. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
* Participant has QT interval by Fredericia (QTcF) =\< 470 msec.
* Participant agrees not to participate in another interventional study while receiving study Intervention in the present study.
* Participant has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Participant has predicted life expectancy \>= 12 weeks.
* Participant must meet all of criteria based on laboratory tests within 7 days prior to the first dose of study Intervention. In case of multiple laboratory data within this period, the most recent data should be used. If a participant has received a recent blood transfusion, the laboratory tests must be obtained \>= 1 week after any blood transfusion.
Monotherapy Disease specific Criteria: Gastric/GEJ Cancer
* Participant has histologically confirmed metastatic, locally advanced unresectable gastric/gastroesophageal junction (GEJ) adenocarcinoma.
* Escalation: Participant with gastric/GEJ adenocarcinoma who has progressed, is intolerant, has refused, or for whom there is no standard approved therapies that impart significant clinical benefit (no limit to the number of prior treatment regimens).
* Unique to South Korea: Participant with gastric/GEJ adenocarcinoma who has refused standard approved therapies is not allowed.
* Expansion: Participant with gastric/GEJ adenocarcinoma must have received no more than 3 prior lines of systemic chemotherapy treatment.
* Unique to EU: Expansion: Participant with gastric/GEJ adenocarcinoma must have received at least first-line standard therapies in the metastatic setting, must have received ramucirumab treatment if eligible \& where ramucirumab is available, \& no more than 3 prior lines of systemic chemotherapy treatment.
Monotherapy Disease specific Criteria: Pancreatic Cancer
* Participant has histologically or cytologically confirmed metastatic pancreatic adenocarcinoma.
* Escalation: Participant with pancreatic adenocarcinoma who has progressed, is intolerant, has refused, or for whom there is no standard approved therapies that impart significant clinical benefit (no limit to the number of prior treatment regimens).
* Unique to South Korea: Participant with pancreatic adenocarcinoma who has refused standard approved therapies is not allowed.
* Expansion: Participants with pancreatic adenocarcinoma must have received no more than 2 prior lines of systemic chemotherapy treatment.
Note: Participants with locally advanced unresectable pancreatic adenocarcinoma will not be admitted in monotherapy arms.
* Unique to EU: Participant with pancreatic adenocarcinoma must have received at least first-line standard therapies in the metastatic setting \& no more than 2 prior lines of systemic chemotherapy treatment.
For all participants in combination therapy (CT) administration:
* If a participant has received a recent blood transfusion, the laboratory tests must be obtained ≥ 1 week after any blood transfusion.
Combination Therapy Disease-specific (CTDS) Inclusion Criteria:
ASP2138 in Combination with Pembrolizumab \& mFOLFOX6 as First-line Therapy in Gastric/GEJ Cancer
* Participant has histologically confirmed diagnosis of gastric/GEJ adenocarcinoma.
* Participant has metastatic or locally advanced unresectable gastric/GEJ adenocarcinoma.
* Participant with gastric/GEJ adenocarcinoma has progressed \& must not have been previously treated for metastatic disease with either chemotherapy or prior checkpoint inhibitor therapy.
* Participant has a human epidermal growth factor receptor 2 (HER2)-negative tumor per local testing.
* For CT with oxaliplatin, follow contraception guidelines from time of informed consent through at least 9 months after final study intervention.
(Unique to South Korea: For CT with oxaliplatin, follow contraception guidelines from time of informed consent through at least 15 months after final study intervention for women \& 12 months after final study intervention for men).
Unique to EU:
* Participant must have a PD-L1 CPS ≥ 1.
CTDS Inclusion Criteria:
ASP2138 in Combination with Ramucirumab \& Paclitaxel as Second-line Therapy in Gastric/GEJ Cancer
* Participant has histologically confirmed diagnosis of gastric/GEJ adenocarcinoma.
* Participant has metastatic or locally advanced unresectable gastric/GEJ adenocarcinoma.
* Participant with gastric/GEJ adenocarcinoma must have previously received 1 line of systemic chemotherapy treatment (i.e., documented objective radiological or clinical disease progression after first line platinum \& fluoropyrimidine treatment in the metastatic setting or disease progression during or within 4 months of the last dose of perioperative treatment.
CTDS Inclusion Criteria:
ASP2138 in Combination with mFOLFIRINOX as First-line Therapy in Pancreatic Cancer
* Participant has histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma.
* Participant has confirmed metastatic or locally advanced unresectable pancreatic adenocarcinoma.
* Participant has pancreatic adenocarcinoma, has progressed \& must not have received prior systemic anticancer therapy for their advanced disease.
* For CT with oxaliplatin, follow contraception guidelines from time of informed consent through at least 9 months after final study intervention.
(Unique to South Korea: For CT with oxaliplatin, follow contraception guidelines from time of informed consent through at least 15 months after final study intervention for women \& 12 months after final study intervention for men).
Japan \& Korea Specific:
For All Participants in ASP2138 in Combination with Pembrolizumab \& CAPOX:
\- If a participant has received a recent blood transfusion, the laboratory tests must be obtained ≥ 1 week after any blood transfusion.
CTDS Inclusion Criteria:
ASP2138 in Combination with Pembrolizumab \& CAPOX as First-line Therapy in Gastric/GEJ Cancer
* Participant has histologically confirmed diagnosis of gastric/GEJ adenocarcinoma.
* Participant has metastatic or locally advanced unresectable gastric/GEJ adenocarcinoma.
* Participant with gastric/GEJ adenocarcinoma must not have been previously treated for metastatic disease with either chemotherapy or prior checkpoint inhibitor therapy.
* Participants have a HER2-negative tumor per local testing.
* For CT with oxaliplatin, follow contraception guidelines from time of informed consent through at least 9 months after final study intervention.
Exclusion Criteria:
* Participant has received other investigational agents, or antineoplastic therapy including other immunotherapy or devices concurrently or within 21 days or 5 times the half-life, whichever is shorter, prior to first dose of study intervention administration.
* Participant has any condition which makes the participant unsuitable for study participation.
* Participant has known immediate or delayed hypersensitivity or contraindication to any component of study intervention.
* Participant has had prior severe allergic reaction or intolerance to known ingredients of ASP2138 or other antibodies, including humanized or chimeric antibodies.
* Participant weighs \< 40 kg.
* Participant has received systemic immunosuppressive therapy, including systemic corticosteroids 14 days prior to first dose of study intervention. Participant using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 10 mg per day of prednisone or equivalent), receiving a single daily dose of systemic corticosteroids or receiving systemic corticosteroids as pre-medication for radiologic imaging contrast use are allowed.
* Participant has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent/recurrent vomiting.
* Participant has significant gastric bleeding \&/or untreated gastric ulcers that exclude the participant from participation.
* Participant has symptomatic CNS metastases or participant has evidence of unstable CNS metastases even if asymptomatic (e.g., progression on scans). Participants with previously treated CNS metastases are eligible, if they are clinically stable \& have no evidence of CNS progression by imaging for at least 4 weeks prior to start of study intervention \& are not requiring immunosuppressive doses of systemic steroids (\> 10 mg per day of prednisone or equivalent) for longer than 2 weeks.
* Participant is known to have HIV infection. However, participants with cluster of differentiation (CD4) + T cell counts \>= 350 cells/µL \& no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within the past 6 months are eligible. NOTE: Screening for human immunodeficiency virus (HIV) infection should be conducted per local requirements.
* Participant is known to have active hepatitis B (positive hepatitis B surface antigen \[HBsAg\]) or hepatitis C infection. Testing is required for known history of these infections or as mandated by local requirements. NOTE: Screening for these infections should be conducted per local requirements.
* For participant who is negative for HBsAg, but hepatitis B core antibody (HBc Ab) positive, a hepatitis B virus (HBV) deoxyribonucleic acid (DNA) test will be performed \& if positive the participant will be excluded.
* Participant with positive hepatitis C virus (HCV) serology, but negative HCV ribonucleic acid (RNA) test results are eligible.
* Participant treated for HCV with undetectable viral load results are eligible
* Participant has had within 6 months prior to first dose of study intervention any of the following: unstable angina, myocardial infarction, ventricular arrhythmia requiring intervention or hospitalization for heart failure.
* Participant has active infection requiring systemic therapy that has not completely resolved within 7 days prior to the start of study intervention.
* Participant has active autoimmune disease that has required systemic immunosuppressive treatment within the past 1 month prior to the start of study intervention.
* Participant has a clinically significant disease or co-morbidity that may adversely affect the safe delivery of treatment within this study or make the participant unsuitable for study participation.
* Participant has psychiatric illness or social situations that would preclude study compliance.
* Participant has had a major surgical procedure 28 days before start of study intervention \& has not fully recovered.
* Participant has received radiotherapy metastatic or for locally advanced unresectable gastric/GEJ or metastatic pancreatic adenocarcinoma 14 days prior to start of study intervention \& has NOT recovered from any related toxicity.
* Participant has another malignancy for which treatment is required.
* Participant who has received CLDN18.2-targeted therapy (e.g., zolbetuximab or chimeric antigen receptor CLDN18.2-specific T cells) prior to first dose of study intervention administration is not eligible for dose escalation cohorts. However, a participant who has received CLDN18.2-targeted therapy greater than 28 days or 5 half-lives (whichever is longer) prior to first dose study intervention administration is eligible for dose expansion cohorts only, with the exception of participants who have experienced Grade \>= 3 gastrointestinal toxicity after receiving an CLDN18.2-targeted therapy.
* Participant has a history or complication of interstitial lung disease.
China Specific:
Participant who has received treatment with herbal medications that have known antitumor activity within 28 days prior to first dose of study treatment.
For all participants in CT administration:
* Participant has prior severe allergic reaction; suspected, known immediate or delayed hypersensitivity; or intolerance or contraindication to any study intervention (i.e., pembrolizumab \& mFOLFOX6 \[all components\], ramucirumab \& paclitaxel or mFOLFIRINOX \[all components\]).
* For 5 FU (fluorouracil): Participant has known dihydropyrimidine dehydrogenase (DPD) deficiency. (NOTE: Screening for DPD deficiency should be conducted per local requirements).
* Participants who have received systemic immunosuppressive therapy, including systemic corticosteroids 14 days prior to the first dose of study intervention are generally excluded; however, participants using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 10 mg per day of prednisone or equivalent), receiving a single daily dose of systemic corticosteroids or receiving systemic corticosteroids as pre-medication for radiologic imaging contrast or for chemotherapy (as part of CT administration) are allowed.
* Participant is known to have HIV infection.
* NOTE: Differing from monotherapy administration, participants with CD4+ T cell counts ≥ 350 cells/µL \& no history of AIDS-defining opportunistic infections within the past 6 months remain ineligible.
* NOTE: Screening for HIV infection should be conducted per local requirements.
* Participant has had uncontrolled high blood pressure within 6 months prior to the first dose of study intervention (Unique to EU: high blood pressure Stage 2 is defined as ≥ 140/90 mmHg).
* Participant has a history of ascites requiring drainage more than twice in the past 7 days.
CTDS Exclusion Criteria:
ASP2138 in Combination with Pembrolizumab \& mFOLFOX6 as First-line Therapy in Gastric/GEJ Cancer:
* Participant has history of (non-infectious) pneumonitis that required steroids, current pneumonitis, or has a history of interstitial lung disease.
* Participant received live-virus vaccination within 30 days prior to the first dose of study intervention.
* Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention or has been diagnosed with an autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Patients that require replacement therapy (e.g., thyroxine \[T4\], insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) may be enrolled.
CTDS Exclusion Criteria:
ASP2138 in Combination with Ramucirumab \& Paclitaxel as Second-line Therapy in Gastric/GEJ Cancer:
* History of cerebrovascular accident or transient ischemic attack within 6 months prior to study intervention.
* Participant has significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to study intervention.
* Participant has evidence of a bleeding diathesis or significant coagulopathy.
* Participant has initiated new treatment with medications that affect the coagulation cascade with an INR ≥ 2 such as vitamin K antagonists, heparins \& direct thrombin inhibitors or the use of factor Xa inhibitors within 28 days prior to the start of study intervention.
Note: If the participant started receiving such medications more than 28 days prior to the start of study intervention \& needs to continue, this is allowed. However, new anticoagulation medications may not be initiated within 28 days prior to the start of study intervention.
Japan \& Korea Specific:
For All Participants in ASP2138 in Combination with Pembrolizumab \& CAPOX:
* Participant has prior severe allergic reaction; suspected, known immediate or delayed hypersensitivity; or intolerance or contraindication to any study intervention (i.e., pembrolizumab \& CAPOX \[all components\]).
* Participants who have received systemic immunosuppressive therapy, including systemic corticosteroids 14 days prior to the first dose of study intervention are generally excluded, however, participants using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 10 mg per day of prednisone or equivalent), receiving a single dose of systemic corticosteroids or receiving systemic corticosteroids as pre-medication for radiologic imaging contrast or for chemotherapy (as part of CT administration) are allowed.
* Participant is known to have HIV infection.
* NOTE: Differing from monotherapy administration, participants with CD4+ T cell counts ≥ 350 cells/μL \& no history of AIDS-defining opportunistic infections within the past 6 months remain ineligible.
* NOTE: Screening for HIV infection should be conducted per local requirements.
* Participant has had uncontrolled high blood pressure within 6 months prior to the first dose of study intervention.
* Participant has a history of ascites requiring drainage more than twice in the past 7 days.
* Participant has known DPD deficiency. (NOTE: Screening for DPD deficiency should be conducted per local requirements).
CTDS Exclusion Criteria:
ASP2138 in Combination with Pembrolizumab \& CAPOX as First-line Therapy in Gastric/GEJ Cancer:
* Participant has history of (noninfectious) pneumonitis that required steroids, current pneumonitis, or has a history of interstitial lung disease.
* Participant received live-virus vaccination within 30 days prior to the first dose of study intervention.
* Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention or has been diagnosed with an autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Participants who require replacement therapy (e.g., thyroxine \[T4\], insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) may be enrolled. DRUG: ASP2138, DRUG: Pembrolizumab, DRUG: Oxaliplatin, DRUG: Leucovorin, DRUG: Fluorouracil, DRUG: Ramucirumab, DRUG: Paclitaxel, DRUG: Irinotecan, DRUG: Capecitabine
Gastric Adenocarcinoma, Gastroesophageal Junction (GEJ) Adenocarcinoma, Pancreatic Adenocarcinoma, Other Digestive Organ, Pancreas, Small Intestine, Stomach
Claudin (CLDN) 18.2, ASP2138, Pharmacokinetics, Safety, Tolerability
UT Southwestern
Genetic Testing to Select Therapy for the Treatment of Advanced or Metastatic Kidney Cancer, OPTIC RCC Study
This phase II trial tests whether using genetic testing of tumor tissue to select the optimal treatment regimen works in treating patients with clear cell renal cell (kidney) cancer that has spread to other places in the body (advanced or metastatic). The current Food and Drug Administration (FDA)-approved regimens for advanced kidney cancer fall into two categories. One treatment combination includes two immunotherapy drugs (nivolumab plus ipilimumab), which are delivered by separate intravenous infusions into a vein. The other combination is one immunotherapy drug (nivolumab infusion) plus an oral pill taken by mouth (cabozantinib). Nivolumab and ipilimumab are "immunotherapies" which release the brakes of the immune system, thus allowing the patient's own immune system to better kill cancer cells. Cabozantinib is a "targeted therapy" specifically designed to block certain biological mechanisms needed for growth of cancer cells. In kidney cancer, cabozantinib blocks a tumor's blood supply. The genetic (DNA) makeup of the tumor may affect how well it responds to therapy. Testing the makeup (genes) of the tumor, may help match a treatment (from one of the above two treatment options) to the specific cancer and increase the chance that the disease will respond to treatment. The purpose of this study is to learn if genetic testing of tumor tissue may help doctors select the optimal treatment regimen to which advanced kidney cancer is more likely to respond.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years and over
PHASE2
NCT05361720
STU-2023-0365
Inclusion Criteria:
* Histological confirmation of RCC with a clear cell component
* Advanced (not amenable to curative surgery or radiation therapy) or metastatic (American Joint Committee on Cancer \[AJCC\] stage IV) RCC
* Patient can comprehend and sign the study informed consent form
* Male or female \>= 18 years of age at the time of informed consent
* Karnofsky performance status (KPS) of \>= 70%
* No prior systemic therapy for RCC in the neoadjuvant, adjuvant or metastatic setting
* At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* Tumor tissue for ribonucleic acid (RNA)-sequencing (tumor tissue from bony metastasis is not suitable but a soft tissue component around bone is acceptable)
* Screening tissue consent- Patient must be assigned to either Cluster 1/2 or 4/5. Patients assigned to cluster 3/6/7 will not be eligible for the treatment study
* Adequate renal function defined as calculated creatinine clearance \>= 30 mL/min per the Cockcroft and Gault formula
* Adequate liver function defined by:
* Total bilirubin =\< 1.5 times the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia of Gilbert's syndrome
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x ULN
* Women of childbearing potential (WOCBP) must have a negative serum pregnancy test during screening and prior to receiving first dose of protocol-indicated treatment
* Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or is not postmenopausal
* Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 years of age in the absence of other biological or physiological causes
Exclusion Criteria:
* =\< 14 days before first dose of protocol-indicated treatment:
* Major surgery requiring general anesthesia
* Inadequately controlled hypertension (systolic blood pressure \[SBP\] \> 160/90 mmHg)
* Anti-hypertensive medications are permitted.
* Active infection requiring infusional treatment
* Has preexisting gastrointestinal or non-gastrointestinal fistula
* Proteinuria \> 2 g/ 24 hours (hrs)
* If patient has 1+ protein on urine dipstick then a 24 hr urine collection is required
* Non-healing wounds on any part of the body (for patients assigned to Cabo/Nivo only)
* Known clinically significant active bleeding including hemoptysis
* Inability to swallow oral medication; or the presence of a poorly controlled gastrointestinal disorder that could significantly affect the absorption of oral study drug (for patients assigned to Cabo/Nivo only) - e.g., Crohn's disease, ulcerative colitis, chronic diarrhea (defined as \> 4 loose stools per day), malabsorption, or bowel obstruction
* Significant cardiovascular disease or condition including:
* Class III or IV cardiovascular disease according to the New York Heart Association (NYHA) functional criteria
* Unstable angina pectoris (i.e., last episode =\< 3 months prior to first dose of protocol-indicated treatment)
* Myocardial infarction within 3 months prior to starting treatment
* Subjects with central nervous system (CNS) metastases are eligible after they have completed local therapy (e.g., whole brain radiation therapy \[WBRT\], surgery or radiosurgery)
* Any condition requiring systemic treatment with either systemic corticosteroids (\> 10 mg/day prednisone or equivalent daily) or other immunosuppressive medications within 14 days prior to initiating protocol-indicated treatment
* In the absence of active autoimmune disease: Subjects are permitted the use of corticosteroids with minimal systemic absorption (e.g., topical, ocular, intra-articular, intranasal, and inhalational), =\< 10 mg/day prednisone or equivalent daily; and physiologic replacement doses of systemic corticosteroids =\< 10 mg/day prednisone or equivalent daily (e.g., hormone replacement therapy needed in patients with hypophysitis) DRUG: Cabozantinib, BIOLOGICAL: Ipilimumab, BIOLOGICAL: Nivolumab
Advanced Clear Cell Renal Cell Carcinoma, Metastatic Clear Cell Renal Cell Carcinoma, Stage III Renal Cell Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8, Kidney
UT Southwestern
Testing of Tazemetostat in Combination With Topotecan and Pembrolizumab in Patients With Recurrent Small Cell Lung Cancer
This phase I trial tests the safety, side effects, and best dose of tazemetostat in combination with topotecan and pembrolizumab in treating patients with small cell lung cancer that has come back after a period of improvement (recurrent). Tazemetostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving tazemetostat in combination with topotecan and pembrolizumab may shrink or stabilize recurrent small cell lung cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Jonathan Dowell
ALL
18 Years and over
PHASE1
NCT05353439
STU-2023-0503
Inclusion Criteria:
* Patients enrolled to the primary cohort must have limited- or extensive-disease SCLC at diagnosis, with relapse at study entry with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, and with prior therapy with platinum doublet. Patients with extensive stage disease should have received chemo-immunotherapy. Both platinum-sensitive and platinum-resistant patients will be included
* Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of pembrolizumab in combination with tazemetostat and topotecan in patients \< 18 years of age, children are excluded from this study
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 70%)
* Leukocytes \>= 3000/mcL
* Absolute neutrophil count \>= 1,500/mcL
* Platelets \>= 100,000/mcL
* Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L
* Total bilirubin =\< 1.5 institutional upper limit of normal (ULN) OR direct bilirubin =\< ULN for patients with total bilirubin levels \> 1.5 × ULN
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN
* Creatinine =\< 1.5 institutional ULN OR glomerular filtration rate (GFR) \>= 60 mL/min/1.73 m\^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m\^2
* Note: Creatinine clearance (CrCl) should be calculated per institutional standard. Glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl
* International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 × ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
* Activated (a)PTT =\< 1.5 × ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load (CD4 count of greater than 250 cells/mcL) within 6 months are eligible for this trial. They must not be receiving prophylactic therapy for an opportunistic infection
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with treated brain metastases are eligible if they are symptomatically stable while off steroid therapy for a minimum of 7 days
* Patients should be class 2B or better on the New York Heart Association Functional Classification
* Ability to understand and the willingness to sign a written informed consent document
* The effects of pembrolizumab and tazemetostat on the developing human fetus are unknown. For this reason and because monoclonal antibodies, EZH2 inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study treatment and for 6 months after the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of study treatment administration
Exclusion Criteria:
* Patients who have had chemotherapy, immune checkpoint inhibitors, or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
* Note: Patients who have had palliative radiotherapy may be included as long as they have recovered from any radiotherapy related adverse events (allow at least 3 days between radiotherapy completion and study treatment)
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1).
* Note: Patients with =\< grade 2 neuropathy or =\< grade 2 alopecia are an exception to this criterion and may qualify for the study
* Note: If patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
* Untreated immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the study principal investigator (PI)
* Patients who are receiving any other investigational agents
* Patients with symptomatic brain metastasis are not eligible due to their extremely poor prognosis and since it is unclear whether the investigational agent penetrates the blood-brain barrier. However, subjects who have had treatment for their brain metastasis and are symptomatically stable while off steroid therapy for a minimum of 7 days may be enrolled. The use of physiologic doses of corticosteroids may be approved after consultation with the study PI
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab and tazemetostat or other agents used in study
* Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
* Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
* Patients with uncontrolled intercurrent illness but not limited to, ongoing or active infection, interstitial lung disease or active, non-infectious pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Patients with psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant women are excluded from this study because pembrolizumab as a monoclonal antibody, and tazemetostat as a EZH2 inhibitor may have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with pembrolizumab or tazemetostat, breastfeeding should be discontinued if the mother is treated with these agents and for 1 week after the last dose of tazemetostat. These potential risks may also apply to other agents used in this study
* Has known active hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C
* Has received a live vaccine within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted
* Has thrombocytopenia, neutropenia, or anemia of grade \>= 3 (per Common Terminology Criteria for Adverse Events \[CTCAE\] 5.0 criteria) or any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS)
* Has abnormalities known to be associated with MDS (e.g. del 5q, chromosome \[chr\] 7 abnormality \[abn\]) and myeloproliferative neoplasm (MPN) (e.g. JAK2 V617F) observed in cytogenetic testing and DNA sequencing
* Has a prior history of T-cell lymphoblastic lymphoma (T-LBL), T-cell acute leukemia (T-ALL) or B-cell acute lymphoblastic leukemia (B-ALL) PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, BIOLOGICAL: Pembrolizumab, DRUG: Tazemetostat Hydrobromide, DRUG: Topotecan Hydrochloride
Extensive Stage Lung Small Cell Carcinoma, Limited Stage Lung Small Cell Carcinoma, Platinum-Resistant Lung Small Cell Carcinoma, Platinum-Sensitive Lung Small Cell Carcinoma, Recurrent Extensive Stage Lung Small Cell Carcinoma, Recurrent Lung Small Cell Carcinoma, Lung/Thoracic
UT Southwestern
Testing the Addition of Stereotactic Radiation Therapy With Immune Therapy for the Treatment of Patients With Unresectable or Metastatic Renal Cell Cancer, SAMURAI Trial (SAMURAI)
This phase II trial tests whether the addition of radiation to the primary tumor, typically given with stereotactic ablative radiation therapy (SABR), in combination with standard of care immunotherapy improves outcomes in patients with renal cell cancer that is not recommended for surgery and has spread from where it first started (primary site) to other places in the body (metastatic). Radiation therapy uses high energy photons to kill tumor cells and shrink tumors. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses of radiation over a shorter period and cause less damage to normal tissue. Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, avelumab, and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Axitinib, cabozantinib, and lenvatinib are in a class of medications called antiangiogenic agents. They work by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving SABR in combination with standard of care immunotherapy may help shrink or stabilize the cancer in patients with renal cell cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Raquibul Hannan
ALL
18 Years and over
PHASE2
NCT05327686
STU-2023-0448
Inclusion Criteria:
* Pathologically (histologically or cytologically) proven diagnosis of renal cell carcinoma prior to registration
* Node-positive unresectable (TxN1Mx) or metastatic (TxNxM1) based on the following diagnostic workup:
* History/physical examination within 45 days prior to registration
* CT/magnetic resonance imaging (MRI) of the chest/abdomen/pelvis within 45 days prior to registration
* Patients must have IMDC intermediate (1-2 factors) or poor risk disease (\>= 3 factors)
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with measurable disease (node positive or metastatic) as defined by RECIST version 1.1 excluding the primary renal tumor
* Patient not recommended for or refused immediate cytoreductive nephrectomy
* Candidate for standard of care therapy with either immuno-oncology (IO)-IO or IO-VEGF combination regimen
* Primary renal tumor measuring 20 cm or less in anterior to posterior dimension only on axial imaging
* Age \>= 18
* Karnofsky performance status \>= 60 within 45 days prior to registration
* Hemoglobin \>= 8 g/dL (transfusions are allowed) (within 45 days prior to registration)
* Platelet count \>= 50,000/mm\^3 (within 45 days prior to registration)
* Absolute neutrophil count (ANC) \>= 1500/mm\^3 (within 45 days prior to registration)
* Calculated (Calc.) creatinine clearance \>= 30 mL/min (within 45 days prior to registration)
* Creatinine clearance (CrCl) \>= 30 mL/min estimated by Cockcroft-Gault Equation
* For African American patients specifically whose renal function is not considered adequate by the formula above, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) should be used for calculating the related estimated glomerular filtration rate (GFR) with a correction factor for African American race creatinine clearance for trial eligibility, where GFR \>= 30 mL/min/1.73m\^2 will be considered adequate
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL) (within 45 days prior to registration)
* Aspartate aminotransferase and alanine aminotransferase (AST and ALT) =\< 3 x upper limit of normal (ULN) or \< 5 x ULN if hepatic metastases present (within 45 days prior to registration)
* Patients with known human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Testing is not required for entry into protocol
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. Patients with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load
* The patient must agree to use a highly effective contraception, including men with vasectomies if they are having sex with a woman of childbearing potential or with a woman who is pregnant, while on study drug and for 6 months following the last dose of study drug. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
Exclusion Criteria:
* Patients with planned treatment of all metastatic disease with definitive therapy including either surgery, ablative (non-palliative) doses of radiation, or intervention of some type (definitive interventional radiology techniques) to ALL metastatic sites rendering the patient without extra-renal measurable disease. Patients NOT planned for definitive treatment of all metastatic sites are eligible. Lesions radiated palliatively are not eligible for response assessment
* Patients with untreated or unstable brain metastases or cranial epidural disease
* Note: Patients who have been adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator are eligible. Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator
* Prior radiotherapy to the kidney that would result in overlap of radiation therapy fields treatment of the primary tumor
* Any systemic therapy for metastatic renal cell carcinoma (RCC) that was initiated \> 90 days before registration, note that prior chemotherapy for a different cancer is allowed (completed \> 3 years prior to registration)
* Severe, active comorbidity defined as follows:
* Active autoimmune disease requiring ongoing therapy including systemic treatment with corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications daily. Inhaled steroids and adrenal replacement steroid doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
* History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies
* Active tuberculosis (purified protein derivative \[PPD\] response without active tuberculosis \[TB\] is allowed)
* Uncontrolled hypertension (systolic blood pressure \[BP\] \>= 190 mmHg or diastolic BP \> 110 mmHg)
* Major surgery requiring hospital admission =\< 28 days prior to registration
* Any serious (requiring hospital stay or long term rehab) non-healing wound, ulcer, or bone fracture within 45 days prior to registration
* Any arterial thrombotic (ST elevation myocardial infarction \[STEMI\], non-ST elevation myocardial infarction \[NSTEMI\], cerebrovascular accident \[CVA\], etc) events within 180 days prior to registration
* Active New York (NY) Heart Association class 3-4 heart failure symptoms
* Moderate or severe hepatic impairment (Child-Pugh B or C)
* Any history of untreated pulmonary embolism or deep venous thrombosis (DVT) within 180 days prior to registration. (Any asymptomatic or treated pulmonary embolism or asymptomatic treated deep venous thrombosis \> 30 days prior to registration is allowed)
* Unstable cardiac arrhythmia within 180 days prior to registration
* History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, bowel obstruction, or gastric outlet obstruction within 180 days prior to registration
* History of or active inflammatory bowel disease
* Malabsorption syndrome within 45 days prior to registration
* Pregnancy and individuals unwilling to discontinue nursing. For women of child bearing potential must have a negative pregnancy test =\< 45 days prior to registration BIOLOGICAL: Avelumab, DRUG: Axitinib, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, DRUG: Cabozantinib, PROCEDURE: Computed Tomography, BIOLOGICAL: Ipilimumab, DRUG: Lenvatinib, PROCEDURE: Magnetic Resonance Imaging, BIOLOGICAL: Nivolumab, BIOLOGICAL: Pembrolizumab, RADIATION: Stereotactic Ablative Radiotherapy
Metastatic Renal Cell Carcinoma, Stage III Renal Cell Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8, Unresectable Renal Cell Carcinoma, Kidney
UT Southwestern; Parkland Health & Hospital System
Neoadjuvant Lenvatinib and Pembrolizumab for IVC Tumor Thrombus
This study will be evaluating safety and efficacy of the combination of lenvatinib and pembolizumab neoaadjuvant therapy prior to surgical resection of locally advanced renal cell carcinoma with IVC tumor thrombus.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Vitaly Margulis
ALL
18 Years and over
PHASE2
NCT05319015
STU-2021-1240
Inclusion Criteria:
• Male/female participants who are at least 18 years of age on the day of signing informed consent
• Have histologically confirmed cT3-4,N0-1,M0-1 (clinical stage III-IV) diagnosis of renal cell carcinoma (any subtype) with level II-IV inferior vena cava tumor thrombus as per the Mayo classification of macroscopic venous invasion in renal cell carcinoma:
• Level 1 tumor thrombus is either at the entry of renal vein or within the IVC \< 2 cm from the confluence of renal vein and IVC
• Level II tumor thrombus extends within the IVC \> 2 cm above the confluence of renal vein and IVC, but still remains below the hepatic veins.
• Level III tumor Thrombus involves the intrahepatic IVC.
• Level IV tumor thrombus extends above diaphragm or into the right atrium.
• The primary tumor and thrombus may be assessed to be resectable or unresectable at the time of enrollment.
• Male participants: A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the 120 day neoadjuvant treatment period and for at least 90 days after the last dose of study treatment and refrain from donating sperm during this period. Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 30 days after the last dose of study treatment.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 14 days prior to the first dose of study intervention.
• Criteria for known Hepatitis B and C positive subjects Hepatitis B and C screening tests are not required unless: * Known history of HBV or HCV infection * As mandated by local health authority Hepatitis B positive subjects: Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization. Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention. Hepatitis C positive subjects: Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening.
• Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization
• HIV-positive participants may be enrolled.
• HIV-infected participants must have well-controlled HIV on ART, defined as: 1\. Participants on ART must have a CD4+ T-cell count ≥350 cells/mm3 at the time of screening 2. Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 or the LLOQ (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening 3. It is advised that participants must not have had any AIDS-defining opportunistic infections within the past 12 months. 4\. Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before study entry (Day 1) and agree to continue ART throughout the study 5. The combination ART regimen must not contain any antiretroviral medications that interact with CYP3A4 inhibitors/inducers/substrates (https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers) 12\. Have adequate organ function as defined in the following table (Table 4). Specimens must be collected within 14 days prior to the start of study intervention.
Exclusion Criteria:
• A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• Has received prior systemic anti-cancer therapy including investigational agents prior to allocation.
• Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. COVID-19 vaccines are permitted provided they are not live attenuated vaccines.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention with the exception of participating in the exploratory imaging trial utilizing 89Zr-DFO-Atezolizumab ImmunoPET/CT (STU-2019-0714).
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past year. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical cancer, bladder in situ) that have undergone potentially curative therapy are not excluded.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
• Has more than three different sites of metastatic renal cell carcinoma.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and lenvatinib and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
• Has had an allogenic tissue/solid organ transplant.
• Has prolongation of QTcF interval to \>480 ms.
• Has a left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range, as determined by multigated acquisition (MUGA) or echocardiogram (ECHO).
• Patients with an ejection fraction (LVEF) of 50 or greater are eligible to enroll on the study
• Patients with an ejection fraction (LVEF) of 40 to 49 are eligible to enroll on the study if they they DO NOT have signs of New York Heart Association Class III or IV congestive heart failure: i. NYHA Class III signs of congestive heart failure include marked limitation of physical activity - ordinary activity or movements cause significant fatigue, heart palpitations, or shortness of breath ii. NYHA Class IV signs of congestive heart failure include being unable to carry out physical activity without discomfort, having symptoms of heart failure at rest, if physical activity or movement is undertaken, discomfort increase c. Patients with an ejection fraction (LVEF) of 39 or less are not eligible to enroll on the study.
• Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. Note: Medically controlled arrhythmia would be permitted.
• If urinalysis reveals proteinuria of 2+ or 500mg/dL greater based on the scale below, the patient will need to undergo a 24 hour urine collection, if the patient has 2000mg/24 hour or great of protein in the 24 hour the urine collection they are NOT ELIGIBLE for the study. If urinalysis protein is negative, trace, 1+, or urinalysis protein is reported in the range 0-499mg/dL protein, the patient IS ELIGIBLE to enroll on the study and does not need to complete a 24 hour urine collection:
• 1+ = 200 - 500 mg/24 hours
• 2+ = 500 - 1500 mg/24 hours
• 3+ = over 2500 mg/24 hours
• 4+ = over 3000 mg/24 hours.
• Uncontrolled blood pressure defined as consistently elevated blood pressure with a Systolic BP\>140 mmHg or diastolic BP \>90 mmHg in spite of an optimized regimen of antihypertensive medication are not able to enroll on the study. However, patients with borderline, isolated, or occasional elevation of blood pressure readings are eligible to enroll on the trial. If the treating physician believes the blood pressure elevation is transient the patient may enroll and blood pressure will be monitored during the study. Patients with persistent hypertension may be initiated on antihypertensive medication by the treating physician if deemed necessary and may enroll on the study. The treating physician may also adjust antihypertensive medication in the attempt to achieve a normal blood pressure while the patient is in screening and on study. It is at the discretion of the enrolling physician to continue adjusting the hypertension medication while the patient is enrolled and treated on the study to maintain adequate blood pressure readings.
• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
• Patients with active Hepatitis B infection (defined as HBsAg positive and/or detectable HBV DNA).
• Patients with active Hepatitis C infection (defined as anti-HCV Ab positive and detectable HCV RNA).
• Hepatitis B and C screening tests are not required unless there is a known history of HBV and HCV infection or as mandated by local health authority.
DRUG: Neoadjuvant Lenvatinib, DRUG: Neoadjuvant Pembrolizumab, PROCEDURE: Radical nephrectomy, IVC thrombectomy, retroperitoneal lymph node dissection, DRUG: Adjuvant Pembrolizumab
Renal Cell Carcinoma, Kidney, Cardiovascular
Renal Cell Carcinoma, IVC tumor thrombus, Neoadjuvant therapy, Immunotherapy, Nephrectomy
UT Southwestern
SIGMA (Safusidenib in IDH1 Mutant Glioma Maintenance) (SIGMA)
This is a 3-part study. The purpose of Part 1 of the study is to evaluate the efficacy, safety, and pharmacokinetic (PK) characteristics of safusidenib in participants with recurrent/progressive IDH1-mutant World Health Organization (WHO) Grade 2 or Grade 3 glioma. The purpose of Part 2 will be to evaluate the efficacy of maintenance safusidenib treatment versus placebo in IDH1-mutant Grade 2 or Grade 3 astrocytoma with high-risk features or IDH1-mutant Grade 4 astrocytoma, following standard-of-care radiation or chemoradiation and adjuvant temozolomide. Part 2 will be randomized, double-blind, and placebo-controlled. The purpose of Part 3 will be to evaluate the efficacy of safusidenib in participants with residual or recurrent IDH1-mutant Grade 3 oligodendroglioma who have received surgery as their only treatment. Part 3 will be an open-label single-arm cohort and will enroll participants concurrently with Part 2.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Michael Youssef
ALL
18 Years to old
PHASE3
NCT05303519
STU20251570
Key Inclusion Criteria for Part 1:
• Patient must be ≥ 18 years of age at the time of signing the informed consent form (ICF).
• Patient must have histologically confirmed recurrent or progressive WHO Grade 2 glioma or Grade 3 glioma with IDH1 R132H or R132C mutation confirmed by immunohistochemistry or molecular genetic testing.
• The IDH mutation, and other applicable gene/molecular alterations (see Table 10-2) are determined by a validated assay as performed in Clinical Laboratory Improvement Amendments (CLIA)-certified/College of American Pathologists (CAP)-accredited or locally equivalent clinical laboratories. Prior clinical pathology report fulfilling the diagnosis criteria prior to screening with tumor samples collected is acceptable for patient enrollment in both Part 1 and Part 2.
• Patient has received no more than 2 prior therapies for disease recurrence/progression.
• Patient has disease recurrence or progression or cannot tolerate the most recent therapy.
• Patient must have a measurable lesion(s) as per the RANO-HGG criteria for primarily enhancing lesions or RANO-LGG criteria for primarily non-enhancing lesions. The lesion (s) must be visible on 2 or more axial slices and have perpendicular diameters of at least 10 × 10 mm. The definition of primarily enhancing lesions or primarily non-enhancing lesions is referred to Section 8.3.1. Key Inclusion Criteria for Part 2 and 3:
• Must be ≥18 years old at the time of signing the ICF.
• Must agree to submit sufficient tumor tissue for retrospective biomarker and histological analyses. This requirement may be waived in rare circumstances with approval by the Sponsor.
• Has adequate hematologic and organ function Key Inclusion Criteria for Part 2:
• Diagnosis of histologically confirmed IDH1-mutant Grade 2, Grade 3 with high risk features or Grade 4 astrocytoma, per WHO 2021 classification and Investigator Assessment.
• Have an IDH1 mutation (R132H/C/G/S/L) based on IHC (R132H only), polymerase chain reaction (PCR), or next-generation sequencing (NGS). CDKN2A/B status and at least 1 of the following must be confirmed: absence of 1p19q co-deletion by fluorescence in situ hybridization, array comparative genomic hybridization, or NGS; presence of an ATRX loss of function mutation by NGS; or loss of normal ATRX expression by IHC. A validated assay performed in a CLIA-certified/CAP-accredited (or local equivalent) clinical laboratory must be used for all of the aforementioned results. Documentation of biomarker status, including redacted molecular pathology and NGS reports, must be provided during Screening.
• Must not have experienced tumor recurrence or progression between first day of radiotherapy and randomization by local assessment per RANO 2.0.
• Participants must have completed radiation therapy with a minimum of 80% of planned treatment completed (with or without concurrent temozolomide) and between 6 and 12 cycles of adjuvant . Randomization must occur at least 28 days and not more than 75 days after the final dose of temozolomide. Key Inclusion Criteria for Part 3:
• Have had at least 1 prior surgery for glioma (biopsy, sub-total resection, or gross total resection), with the most recent surgery having occurred at least 90 days and no longer than 5 years before the date of enrollment, have not had any other prior anticancer therapy, including chemotherapy and radiotherapy, and are not in need of immediate chemotherapy or radiotherapy in the opinion of the Investigator.
• Have histologically confirmed Grade 3 IDH-mutant oligodendroglioma according to WHO 2021 criteria per local assessment.
• Have residual or recurrent measurable disease per RANO 2.0 and confirmed by BICR, at the time of enrollment.
• Have an IDH1 mutation (R132H/C/G/S/L). The presence of 1p19q co-deletion must also be confirmed. All results must be generated using a validated assay performed in a CLIA-certified/CAP-accredited (or local equivalent) clinical laboratory. Key Exclusion Criteria for Part 1:
• Prior anti-cancer therapy, within the applicable periods shown below, before the start of the protocol treatment:
• Systemic drug therapies: within 3 weeks (lomustine within 6 weeks)
• Surgery: within 3 weeks
• Radiation therapy: within 12 weeks
• Investigational agents: within 5 half-lives for other investigational agents
• Patient did receive the prior therapy targeted to IDH1 mutation..
• Known hypersensitivity to safusidenib or to any drug with similar chemical structure or to any other excipient present in the pharmaceutical form of safusidenib. Key Exclusion Criteria for Part 2 and 3:
• Participants with prior or anticipated treatment with anti-angiogenic agents such as Avastin (bevacizumab), agents known to target IDH1 or IDH2, or investigational agents for glioma are excluded.
• Have brainstem or spinal cord involvement either as primary location, site of multifocal involvement, or by significant tumor extension.
• Significant functional or neurocognitive deficits, including uncontrolled seizures, that would preclude participation in protocol-defined study activities, as assessed by Investigator.
• Evidence of diffuse leptomeningeal disease.
• History of significant cardiac disease within 12 months prior to randomization (if applicable) or first dose of study drug (if randomization does not apply).
• If taking corticosteroids, must be on a stable or decreasing dose for the 14 days prior to randomization (if applicable) or first dose of study drug (if randomization does not apply).
• Participants with other malignancies must have received curative treatment and been disease-free for at least 3 years. Curatively resected skin cancer or curatively treated carcinoma in situ is allowed.
• Have a condition that would interfere with, or increase the risk of, study participation. Key Exclusion Criteria for Part 2 1. Participants may not have received any anticancer treatments other than surgery, radiation, concurrent/adjuvant temozolomide, and tumor-treating fields. Tumor-treating fields must be discontinued prior to randomization. Key Exclusion Criteria for Part 3: 1\. Participants may not have received any prior anticancer therapy other than surgery (biopsy, sub-total, or gross total resection) for treatment of glioma, including radiotherapy.
• Patient must be ≥ 18 years of age at the time of signing the informed consent form (ICF).
• Patient must have histologically confirmed recurrent or progressive WHO Grade 2 glioma or Grade 3 glioma with IDH1 R132H or R132C mutation confirmed by immunohistochemistry or molecular genetic testing.
• The IDH mutation, and other applicable gene/molecular alterations (see Table 10-2) are determined by a validated assay as performed in Clinical Laboratory Improvement Amendments (CLIA)-certified/College of American Pathologists (CAP)-accredited or locally equivalent clinical laboratories. Prior clinical pathology report fulfilling the diagnosis criteria prior to screening with tumor samples collected is acceptable for patient enrollment in both Part 1 and Part 2.
• Patient has received no more than 2 prior therapies for disease recurrence/progression.
• Patient has disease recurrence or progression or cannot tolerate the most recent therapy.
• Patient must have a measurable lesion(s) as per the RANO-HGG criteria for primarily enhancing lesions or RANO-LGG criteria for primarily non-enhancing lesions. The lesion (s) must be visible on 2 or more axial slices and have perpendicular diameters of at least 10 × 10 mm. The definition of primarily enhancing lesions or primarily non-enhancing lesions is referred to Section 8.3.1. Key Inclusion Criteria for Part 2 and 3:
• Must be ≥18 years old at the time of signing the ICF.
• Must agree to submit sufficient tumor tissue for retrospective biomarker and histological analyses. This requirement may be waived in rare circumstances with approval by the Sponsor.
• Has adequate hematologic and organ function Key Inclusion Criteria for Part 2:
• Diagnosis of histologically confirmed IDH1-mutant Grade 2, Grade 3 with high risk features or Grade 4 astrocytoma, per WHO 2021 classification and Investigator Assessment.
• Have an IDH1 mutation (R132H/C/G/S/L) based on IHC (R132H only), polymerase chain reaction (PCR), or next-generation sequencing (NGS). CDKN2A/B status and at least 1 of the following must be confirmed: absence of 1p19q co-deletion by fluorescence in situ hybridization, array comparative genomic hybridization, or NGS; presence of an ATRX loss of function mutation by NGS; or loss of normal ATRX expression by IHC. A validated assay performed in a CLIA-certified/CAP-accredited (or local equivalent) clinical laboratory must be used for all of the aforementioned results. Documentation of biomarker status, including redacted molecular pathology and NGS reports, must be provided during Screening.
• Must not have experienced tumor recurrence or progression between first day of radiotherapy and randomization by local assessment per RANO 2.0.
• Participants must have completed radiation therapy with a minimum of 80% of planned treatment completed (with or without concurrent temozolomide) and between 6 and 12 cycles of adjuvant . Randomization must occur at least 28 days and not more than 75 days after the final dose of temozolomide. Key Inclusion Criteria for Part 3:
• Have had at least 1 prior surgery for glioma (biopsy, sub-total resection, or gross total resection), with the most recent surgery having occurred at least 90 days and no longer than 5 years before the date of enrollment, have not had any other prior anticancer therapy, including chemotherapy and radiotherapy, and are not in need of immediate chemotherapy or radiotherapy in the opinion of the Investigator.
• Have histologically confirmed Grade 3 IDH-mutant oligodendroglioma according to WHO 2021 criteria per local assessment.
• Have residual or recurrent measurable disease per RANO 2.0 and confirmed by BICR, at the time of enrollment.
• Have an IDH1 mutation (R132H/C/G/S/L). The presence of 1p19q co-deletion must also be confirmed. All results must be generated using a validated assay performed in a CLIA-certified/CAP-accredited (or local equivalent) clinical laboratory. Key Exclusion Criteria for Part 1:
• Prior anti-cancer therapy, within the applicable periods shown below, before the start of the protocol treatment:
• Systemic drug therapies: within 3 weeks (lomustine within 6 weeks)
• Surgery: within 3 weeks
• Radiation therapy: within 12 weeks
• Investigational agents: within 5 half-lives for other investigational agents
• Patient did receive the prior therapy targeted to IDH1 mutation..
• Known hypersensitivity to safusidenib or to any drug with similar chemical structure or to any other excipient present in the pharmaceutical form of safusidenib. Key Exclusion Criteria for Part 2 and 3:
• Participants with prior or anticipated treatment with anti-angiogenic agents such as Avastin (bevacizumab), agents known to target IDH1 or IDH2, or investigational agents for glioma are excluded.
• Have brainstem or spinal cord involvement either as primary location, site of multifocal involvement, or by significant tumor extension.
• Significant functional or neurocognitive deficits, including uncontrolled seizures, that would preclude participation in protocol-defined study activities, as assessed by Investigator.
• Evidence of diffuse leptomeningeal disease.
• History of significant cardiac disease within 12 months prior to randomization (if applicable) or first dose of study drug (if randomization does not apply).
• If taking corticosteroids, must be on a stable or decreasing dose for the 14 days prior to randomization (if applicable) or first dose of study drug (if randomization does not apply).
• Participants with other malignancies must have received curative treatment and been disease-free for at least 3 years. Curatively resected skin cancer or curatively treated carcinoma in situ is allowed.
• Have a condition that would interfere with, or increase the risk of, study participation. Key Exclusion Criteria for Part 2 1. Participants may not have received any anticancer treatments other than surgery, radiation, concurrent/adjuvant temozolomide, and tumor-treating fields. Tumor-treating fields must be discontinued prior to randomization. Key Exclusion Criteria for Part 3: 1\. Participants may not have received any prior anticancer therapy other than surgery (biopsy, sub-total, or gross total resection) for treatment of glioma, including radiotherapy.
DRUG: safusidenib, DRUG: Placebo
Glioma, Astrocytoma, Grade IV, IDH1-mutant Glioma, Astrocytoma, IDH-Mutant, Grade 3, Astrocytoma, IDH-Mutant, Grade 4, Astrocytoma, IDH-Mutant, Grade 2, Oligodendroglioma, Oligodendroglioma, IDH-Mutant and 1p/19q-Codeleted, Brain and Nervous System
safusidenib, IDH1-mutant glioma, astrocytoma
UT Southwestern
Chemotherapy for the Treatment of Patients With Newly Diagnosed Very Low-Risk and Low Risk Fusion Negative Rhabdomyosarcoma
Rhabdomyosarcoma is a type of cancer that occurs in the soft tissues in the body. This phase III trial aims to maintain excellent outcomes in patients with very low risk rhabdomyosarcoma (VLR-RMS) while decreasing the burden of therapy using treatment with 24 weeks of vincristine and dactinomycin (VA) and examines the use of centralized molecular risk stratification in the treatment of rhabdomyosarcoma. Another aim of the study it to find out how well patients with low risk rhabdomyosarcoma (LR-RMS) respond to standard chemotherapy when patients with VLR-RMS and patients who have rhabdomyosarcoma with DNA mutations get separate treatment. Finally, this study examines the effect of therapy intensification in patients who have RMS cancer with DNA mutations to see if their outcomes can be improved.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Matthew Campbell
ALL
up to 21 Years old
PHASE3
NCT05304585
STU-2022-0692
Inclusion Criteria:
* All patients must be enrolled on APEC14B1 (NCT02402244) and consented to the Molecular Characterization Initiative (Part A) prior to enrollment and treatment on ARST2032 (this trial).
* Patients must be =\< 21 years at the time of enrollment.
* Patients must have newly diagnosed embryonal rhabdomyosarcoma (ERMS), spindle cell/sclerosing RMS, or FOXO1 fusion negative alveolar rhabdomyosarcoma (ARMS) (institutional FOXO1 fusion results are acceptable). RMS types included under ERMS include those classified in the 1995 International Classification of Rhabdomyosarcoma (ICR) as ERMS (classic, spindle cell, and botryoid variants), which are reclassified in the 2020 World Health Organization (WHO) classification as ERMS (classic, dense and botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical spindle cell ERMS variant and the newly recognized sclerosing RMS variant). Enrollment in APEC14B1 is required for all patients.
* All patients will be evaluated for stage and clinical group. Note that clinical group designation assigned at the time of enrollment on study remains unchanged regardless of any second-look operation that may be performed.
* Patients will be eligible for the very low-risk stratum (Regimen VA) if they have Stage 1, CG I disease.
* Patients will be eligible for the low-risk stratum (Regimen VAC/VA) if they have Stage 1, CG II disease, Stage 2, CG I or II disease, or Stage 1, CG III (orbit only) disease.
* Paratesticular Tumors: Staging ipsilateral retroperitoneal lymph node sampling (SIRLNS) is required for all patients \>= 10 years of age with paratesticular tumors who do not have gross nodal involvement on imaging.
* Extremity Tumors: Regional lymph node sampling is required for histologic evaluation in patients with extremity tumors.
* Clinically or radiographically enlarged nodes must be sampled for histologic evaluation.
* Patients must have a Lansky (for patients =\< 16 years of age) or Karnofsky (for patients \> 16 years of age) performance status score of \>= 50. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing performance score.
* Peripheral absolute neutrophil count (ANC) \>= 750/uL (within 7 days prior to enrollment).
* Platelet count \>= 75,000/uL (transfusion independent) (within 7 days prior to enrollment).
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a serum creatinine (within 7 days prior to enrollment) based on age/gender as follows:
* Age: 1 month to \< 6 months; Maximum serum creatinine (mg/dL): 0.4 (male) : 0.4 (female)
* Age: 6 months to \< 1 year; Maximum serum creatinine (mg/dL): 0.5 (male) : 0.5 (female)
* Age: 1 to \< 2 years; Maximum serum creatinine (mg/dL): 0.6 (male) : 0.6 (female)
* Age: 2 to \< 6 years; Maximum serum creatinine (mg/dL): 0.8 (male) : 0.8 (female)
* Age: 6 to \< 10 years; Maximum serum creatinine (mg/dL): 1 (male) : 1 (female)
* Age: 10 to \< 13 years; Maximum serum creatinine (mg/dL): 1.2 (male) : 1.2 (female)
* Age: 13 to \< 16 years; Maximum serum creatinine (mg/dL): 1.5 (male) : 1.4 (female)
* Age \>= 16 years; Maximum serum creatinine (mg/dL): 1.7 (male) : 1.4 (female)
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment), and
* If there is evidence of biliary obstruction by the tumor, then the total bilirubin must be \< 3 x ULN for age.
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L.
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L
* If there is evidence of biliary obstruction by the tumor, then the total bilirubin must be \< 3 x ULN for age
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* All patients and/or their parents or legal guardians must sign a written informed consent.
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
Exclusion Criteria:
* Patients who have received prior chemotherapy and/or radiation therapy for cancer prior to enrollment. Surgical resection alone of previous cancer(s) is permitted.
* Patients who have received chemotherapy or radiation for non-malignant conditions (e.g., autoimmune diseases) are eligible. Patients must discontinue chemotherapy for non-malignant conditions prior to starting protocol therapy.
* Vincristine is sensitive substrate of the CYP450 3A4 isozyme. Patients must not have received drugs that are moderate to strong CYP3A4 inhibitors and inducers within 7 days prior to study enrollment.
* Patients unable to undergo radiation therapy, if necessary, as specified in the protocol.
* Evidence of uncontrolled infection.
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
* Lactating females who plan to breastfeed their infants.
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation. PROCEDURE: Biopsy Procedure, PROCEDURE: Bone Scan, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, BIOLOGICAL: Dactinomycin, PROCEDURE: Magnetic Resonance Elastography, PROCEDURE: Positron Emission Tomography, RADIATION: Radiation Therapy, DRUG: Vincristine
Embryonal Rhabdomyosarcoma, Fusion-Negative Alveolar Rhabdomyosarcoma, Spindle Cell/Sclerosing Rhabdomyosarcoma, Sarcoma
Children’s Health
Safety and Feasibility of Robotic SP Nipple Sparing Mastectomy
This is a single arm, single-center, prospective clinical trial designed to track the peri, post-operative and oncologic outcomes when utilizing the da-Vinci single port (SP) robotic platform to perform robotic nipple sparing mastectomy (rNSM) and immediate breast reconstruction with tissue expanders/implants and acellular dermal matrix (ADM - Alloderm), for patients with breast cancer as well as those with a high risk for breast cancer. Safety and feasibility measures will be measured as primary outcome measures. Oncological and patient satisfaction outcome measures will be measured. Our hypothesis is that SPr-NSM is equal to open NSM in terms of safety, feasibility and oncological outcomes with improved patient satisfaction as measured by nipple sensation and patient reported outcomes.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Deborah Farr
FEMALE
18 Years to 80 Years old
NA
NCT05245812
STU-2022-0091
Inclusion Criteria:
* Candidates for open nipple sparing mastectomy, per standard of care with regards to anatomic factors and tumor location including: nipple sparing resection and resection OR prophylactic mastectomy for risk reduction OR treatment of ductal carcinoma in-situ or clinically node negative cT1-T3 breast cancer
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Exclusion Criteria:
* Inability to provide informed consent
* Pregnant or nursing women
* Patients with:
* Inflammatory breast cancer
* Skin involvement with tumor
* Pre-operative diagnosis of Nipple Areolar Complex (NAC) tumor involvement
* Grade 3 or higher nipple ptosis
* Contraindicated for general anesthesia or surgery
* Heavy current smoking history (defined as \> 20 cigarettes per day) DEVICE: da Vinci SP Surgical System
Breast Cancer, High Risk of Breast Cancer, Breast - Female
UT Southwestern
Phase 1 Study of MRTX1719 in Solid Tumors With MTAP Deletion
This is a Phase 1, open-label, multicenter, study of the safety, tolerability, PK, PD, and anti-tumor activity of MRTX1719 patients with advanced, unresectable or metastatic solid tumor malignancy with homozygous deletion of the MTAP gene.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Salwan Al Mutar
ALL
18 Years to old
PHASE1
NCT05245500
STU-2024-1089
Inclusion Criteria
* Histologically confirmed diagnosis of a solid tumor malignancy with homozygous deletion of the MTAP gene detected in tumor tissue.
* Unresectable or metastatic disease.
* Presence of a tumor lesion amenable to mandatory biopsy for pharmacodynamic evaluation at baseline and on-study unless Sponsor-confirmed as medically unsafe or infeasible.
* Age ≥ 18 years.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Adequate organ function.
Exclusion Criteria
* Prior treatment with a PRMT5 or MAT2A inhibitor therapy.
* Active brain metastases or carcinomatous meningitis.
* History of significant hemoptysis or hemorrhage within 4 weeks of the first dose of study treatment.
* Major surgery within 4 weeks of first dose of study treatment.
* History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions (eg, uncontrolled nausea, vomiting, malabsorption syndrome) likely to alter absorption of study treatment or result in inability to swallow oral medications.
* Cardiac abnormalities.
* Other protocol-defined Inclusion/Exclusion criteria apply.
DRUG: MRTX1719
Mesothelioma, Non Small Cell Lung Cancer, Malignant Peripheral Nerve Sheath Tumors, Solid Tumor, Pancreatic Adenocarcinoma, Advanced Solid Tumor, Colon, Esophagus, Liver, Lung/Thoracic, Other Digestive Organ, Other Respiratory and Intrathoracic Organs, Pancreas, Small Intestine, Stomach
MTAP Deletion, Mesothelioma, Non Small Cell Lung Cancer, Malignant Peripheral Nerve Sheath Tumors, Solid Tumor, MTAP, Malignant, Pancreatic adenocarcinoma, Pancreas Cancer, PRMT5, Synthetic Lethality, Advanced Solid Tumor, NSCLC
UT Southwestern
Phase 3 Study to Evaluate the Efficacy and Safety of HER2/Neu Peptide GLSI-100 (GP2 + GM-CSF) in HER2/Neu Positive Subjects (FLAMINGO-01)
This is a prospective, randomized, double-blinded, placebo-controlled, multi-center, Phase 3 study of GLSI-100 immunotherapy in HLA-A\*02 positive and HER2/neu positive subjects who are at high risk for disease recurrence and have completed both neoadjuvant and postoperative adjuvant standard of care therapy. Treatment consists of 6 intradermal injections, Primary Immunization Series (PIS), over the first 6 months of treatment and 5 booster intradermal injections spaced 6 months apart. A third open-label arm will explore GLSI-100 immunotherapy in non-HLA-A\*02 positive and HER2/neu positive subjects.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Nisha Unni
ALL
18 Years to 100 Years old
PHASE3
NCT05232916
STU-2023-0621
Inclusion Criteria:
* HLA-A\*02-positive, unless being enrolled in the third non-HLA-A\*02 arm
* Histologically confirmed diagnosis of HER2/neu positive primary breast cancer for all tumors biopsied (multifocal, multicentric, or synchronous contralateral disease)
* Completion of both neoadjuvant and adjuvant trastuzumab-based standard of care breast cancer therapy
* Stage I, II, or III at presentation with pathologic evidence of residual invasive carcinoma in the breast or axillary lymph nodes (residual disease) at surgery following completion of neoadjuvant therapy -OR- Stage III at presentation with pathologic complete response (pCR) at surgery following completion of neoadjuvant therapy
* The subject can begin study therapy within one year of completion of adjuvant trastuzumab-based therapy and any other standard therapies, but, study therapy can be administered concurrently with endocrine therapy.
* No clinical evidence of residual or persistent breast cancer per treating physician assessment
* ECOG 0-2
* Adequate organ function
* Negative pregnancy test or evidence of post-menopausal status
* If of childbearing potential, willing to use a form of highly effective contraception
* Subject must both reside in and have been treated for their cancer in the country in which the clinical site is located.
Exclusion Criteria:
* Stage IV cancer or metastatic breast cancer at any time
* Inflammatory breast cancer
* Receiving other investigational agents
* Receiving chemotherapy
* Requiring long-term systemic treatment with corticosteroids or other immunosuppressive therapy
* History of immunodeficiency or active autoimmune disease
* A history of serious allergic reactions, including anaphylaxis, to human granulocyte-macrophage colony-stimulating factors such as sargramostim, yeast-derived products, or any component of the investigational product
* Other malignancies except adequately treated in situ carcinoma of the cervix or basal cell or squamous cell carcinoma of the skin
* Active infection
* Known HIV infection with a detectable viral load within 6 months of the anticipated start of treatment. Note: Subjects on effective antiretroviral therapy with an undetectable viral load within 6 months of the anticipated start of treatment are eligible for this trial. BIOLOGICAL: Placebo, BIOLOGICAL: GLSI-100
Breast Cancer, Breast - Female, Breast - Male
HER2/neu positive, Residual disease, pCR, Extended adjuvant, GP2, Immunotherapy, HLA type
UT Southwestern; Parkland Health & Hospital System
Thoracotomy Versus Thoracoscopic Management of Pulmonary Metastases in Patients With Osteosarcoma
This phase III trial compares the effect of open thoracic surgery (thoracotomy) to thoracoscopic surgery (video-assisted thoracoscopic surgery or VATS) in treating patients with osteosarcoma that has spread to the lung (pulmonary metastases). Open thoracic surgery is a type of surgery done through a single larger incision (like a large cut) that goes between the ribs, opens up the chest, and removes the cancer. Thoracoscopy is a type of chest surgery where the doctor makes several small incisions and uses a small camera to help with removing the cancer. This trial is being done evaluate the two different surgery methods for patients with osteosarcoma that has spread to the lung to find out which is better.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Matthew Campbell
ALL
up to 50 Years old
PHASE3
NCT05235165
STU-2022-0187
Inclusion Criteria:
* Patients must be \< 50 years at the time of enrollment.
* Patients must have =\< 4 nodules per lung consistent with or suspicious for metastases, with at least one of which being \>= 3 mm and all of which must be =\< 3 cm size.
* Note: Patient must have eligibility confirmed by rapid central imaging review.
* Lung nodules must be considered resectable by either open thoracotomy or thoracoscopic surgery. Determination of resectability is made by the institutional surgeon.
* Patients must have a histological diagnosis of osteosarcoma.
* Patients must have evidence of metastatic lung disease at the time of initial diagnosis, or at time of 1st recurrence following completion of therapy for initially localized disease.
* Patients with newly diagnosed disease must have completed successful gross tumor resection for their primary tumor or surgical local control of primary tumor must be planned to be performed simultaneously with thoracic surgery.
* Newly diagnosed patients must be receiving or recently completed (within 60 days) systemic therapy considered by the treating physician to be standard treatment for newly diagnosed osteosarcoma (eg, cisplatin-doxorubicin or ifosfamide-based drug regimens) at the time of enrollment on this study. Dose and drug modifications for toxicity do not exclude patients from participation.
* Patients at time of 1st recurrence must have completed systemic therapy for their initial primary tumor, considered by the treating physician to be standard treatment for newly diagnosed osteosarcoma (eg, cisplatin-doxorubicin or ifosfamide-based drug regimens) at the time of enrollment on this study. Dose and drug modifications for toxicity do not exclude patients from participation.
Exclusion Criteria:
* Patients with unresectable primary tumor.
* Patients with pulmonary metastatic lesions that would require anatomic resection (lobectomy or pneumonectomy) or lesions that are defined as "central" (i.e., central lesion involves or is proximal to segmental bronchi and peripheral is lesion distal to segmental bronchi).
* Patients with chest wall or mediastinal based metastatic lesions, or with significant pleural effusion.
* Patients with disease progression at either the primary or pulmonary metastatic site while on initial therapy. Note: Once the patient has been enrolled on the study, additional computed tomography (CT) scans are not anticipated prior to thoracic surgery. Note: Some variation in nodule size measurements over the course of pre-operative therapy is anticipated and does not qualify for exclusion unless deemed true disease progression by the primary treatment team.
* Patients with evidence of extrapulmonary metastatic disease.
* Patients who received therapeutic pulmonary surgery for lung metastasis prior to enrollment.
* All patients and/or their parents or legal guardians must sign a written informed consent.
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met. PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, OTHER: Questionnaire Administration, PROCEDURE: Thoracoscopy, PROCEDURE: Thoracotomy
Metastatic Malignant Neoplasm in the Lung, Metastatic Osteosarcoma, Osteosarcoma, Bones and Joints, Lung/Thoracic
Children’s Health
Venetoclax in Children With Relapsed Acute Myeloid Leukemia (AML)
A study to evaluate if the randomized addition of venetoclax to a chemotherapy backbone (fludarabine/cytarabine/gemtuzumab ozogamicin \[GO\]) improves survival of children/adolescents/young adults with acute myeloid leukemia (AML) in 1st relapse who are unable to receive additional anthracyclines, or in 2nd relapse.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kathleen Ludwig
ALL
29 Days to 21 Years old
PHASE3
NCT05183035
STU-2022-0725
Inclusion Criteria
* Participants must have enrolled on APAL2020SC, NCT Number: NCT04726241 prior to enrollment on ITCC-101/APAL2020D. (This is only applicable for participants in USA/Canada/Australia/New Zealand sites/LLS territory).
* Participants must be ≥ 29 days of age and ≤ 21 years of age at enrollment.
* Participants must have one of the following:
* Children, adolescents, and young adults with acute myeloid leukemia without FLT3/internal tandem duplication (ITD) mutation in:
• Second relapse, who are sufficiently fit to undergo another round of intensive chemotherapy
• First relapse who per investigator discretion cannot tolerate additional anthracycline containing chemotherapy. * Participants must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (≥ 50% Lansky or Karnofsky score) * Participants must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to start of protocol treatment:
• Cytotoxic chemotherapy: Must not have received cytotoxic chemotherapy within 14 days prior to start of protocol treatment, except for corticosteroids, low dose cytarabine or hydroxyurea that can be given up to 24 hours prior to start of protocol treatment.
• Intrathecal cytotoxic therapy: No wash-out time is required for participants having received any combination of intrathecal cytarabine, methotrexate, and/or hydrocortisone.
• Antibodies: ≥ 21 days must have elapsed from infusion of last dose of an antibody-drug conjugate before start of protocol treatment. For unmodified antibodies or T cell engaging antibodies, 2 half-lives must have elapsed before start of protocol treatment. Any toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.
• Interleukins, Interferons and Cytokines (other than Hematopoietic Growth Factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors) before start of protocol treatment.
• Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or ≥7 days for short-acting growth factor before start of protocol treatment.
• Radiation therapy (RT) (before start of protocol treatment): * ≥ 14 days have elapsed for local palliative RT (small port); * ≥ 84 days must have elapsed if prior craniospinal RT or if ≥ 50% radiation of pelvis; * ≥ 42 days must have elapsed if other substantial bone marrow (BM) radiation.
• Stem Cell Infusions (before start of protocol treatment): * ≥ 84 days since allogeneic (non-autologous) bone marrow or stem cell transplant (with or without total body irradiation \[TBI\]) or boost infusion (any stem cell product; not including donor lymphocyte infusion \[DLI\]) * No evidence of active graft versus host disease (GVHD).
• Participants who are receiving cyclosporine, tacrolimus or other agents to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial. Participants must be off medications to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant for at least 14 days prior to enrollment.
• Cellular Therapy: ≥ 42 days after the completion of donor lymphocyte infusion (DLI) or any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.) before start of protocol treatment.
• Participants with prior exposure to venetoclax are eligible in this trial * Adequate organ function:
• Adequate Renal Function defined as: * Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 60ml/min/1.73 m\^2, or * Normal serum creatinine based on age/sex
• Adequate Liver Function defined as: * Direct bilirubin \< 1.5 x upper limit of normal (ULN), and * Alkaline phosphatase ≤ 2.5 x ULN, and * Serum glutamic pyruvic transaminase (SGPT) alanine aminotransferase (ALT) ≤ 2.5 x ULN. If liver abnormality is due to radiographically identifiable leukemia infiltrate, the participant will remain eligible.
• Cardiac performance: Minimum cardiac function defined as: * No history of congestive heart failure in need of medical treatment * No pre-treatment diminished left ventricular function on echocardiography (shortening fraction \[SF\] \< 25% or ejection fraction \[EF\] \< 40%) * No signs of congestive heart failure at presentation of relapse. * Participant, parent or guardian must sign and date informed consent and pediatric assent (when required), prior to the initiation of screening or study specific procedures, according to local law and legislation. Exclusion Criteria * Participants who in the opinion of the investigator may not be able to comply with the study requirements of the study, are not eligible. * Participants with Down syndrome. * Participants with Acute promyelocytic leukemia (APL) or Juvenile myelomonocytic leukemia (JMML). * Participants with isolated CNS3 disease or symptomatic CNS3 disease. * Participants with malabsorption syndrome or any other condition that precludes enteral administration of venetoclax. * Participants who are currently receiving another investigational drug (GO is not considered investigational in this study). * Participants with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known congenital bone marrow failure syndrome. * Participants with known prior allergy to any of the medications used in protocol therapy. * Participants with documented active, uncontrolled infection at the time of study entry. * No known human immunodeficiency virus (HIV) infection. * Post menarchal female participants with positive pregnancy test. * Concomitant Medications * Participants who have received strong and moderate CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort within 7 days of the start of study treatment. * Participants who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days of the start of study treatment. * Participants who have hypersensitivity to the active substance or to any of the excipients listed in summary of product characteristics (SPC). * Pregnancy or Breast-Feeding: * Participants who are pregnant or breast-feeding. * Participants of reproductive potential may not participate unless they have agreed to use a highly effective contraceptive method per clinical trials facilitation group (CTFG) guidelines for the duration of study therapy and for 6 months after the completion of all study therapy. * Male participants must use a condom during intercourse and agree not to father a child or donate sperm during therapy and for the duration of study therapy and for 4 months after the completion of all study therapy. Additional criteria to receive a gemtuzumab ozogamicin infusion: Gemtuzumab ozogamicin should not be given: * to participants with history of veno-occlusive disease (VOD)/Sinusoidal obstruction syndrome (SOS) grade 4 * to participants with history of VOD/SOS grade 3 * to participants with CD33 negative leukemic blasts (determined at local lab) Note that these participants are eligible for the study but will not be treated with gemtuzumab ozogamicin.
• Second relapse, who are sufficiently fit to undergo another round of intensive chemotherapy
• First relapse who per investigator discretion cannot tolerate additional anthracycline containing chemotherapy. * Participants must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (≥ 50% Lansky or Karnofsky score) * Participants must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to start of protocol treatment:
• Cytotoxic chemotherapy: Must not have received cytotoxic chemotherapy within 14 days prior to start of protocol treatment, except for corticosteroids, low dose cytarabine or hydroxyurea that can be given up to 24 hours prior to start of protocol treatment.
• Intrathecal cytotoxic therapy: No wash-out time is required for participants having received any combination of intrathecal cytarabine, methotrexate, and/or hydrocortisone.
• Antibodies: ≥ 21 days must have elapsed from infusion of last dose of an antibody-drug conjugate before start of protocol treatment. For unmodified antibodies or T cell engaging antibodies, 2 half-lives must have elapsed before start of protocol treatment. Any toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.
• Interleukins, Interferons and Cytokines (other than Hematopoietic Growth Factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors) before start of protocol treatment.
• Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or ≥7 days for short-acting growth factor before start of protocol treatment.
• Radiation therapy (RT) (before start of protocol treatment): * ≥ 14 days have elapsed for local palliative RT (small port); * ≥ 84 days must have elapsed if prior craniospinal RT or if ≥ 50% radiation of pelvis; * ≥ 42 days must have elapsed if other substantial bone marrow (BM) radiation.
• Stem Cell Infusions (before start of protocol treatment): * ≥ 84 days since allogeneic (non-autologous) bone marrow or stem cell transplant (with or without total body irradiation \[TBI\]) or boost infusion (any stem cell product; not including donor lymphocyte infusion \[DLI\]) * No evidence of active graft versus host disease (GVHD).
• Participants who are receiving cyclosporine, tacrolimus or other agents to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial. Participants must be off medications to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant for at least 14 days prior to enrollment.
• Cellular Therapy: ≥ 42 days after the completion of donor lymphocyte infusion (DLI) or any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.) before start of protocol treatment.
• Participants with prior exposure to venetoclax are eligible in this trial * Adequate organ function:
• Adequate Renal Function defined as: * Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 60ml/min/1.73 m\^2, or * Normal serum creatinine based on age/sex
• Adequate Liver Function defined as: * Direct bilirubin \< 1.5 x upper limit of normal (ULN), and * Alkaline phosphatase ≤ 2.5 x ULN, and * Serum glutamic pyruvic transaminase (SGPT) alanine aminotransferase (ALT) ≤ 2.5 x ULN. If liver abnormality is due to radiographically identifiable leukemia infiltrate, the participant will remain eligible.
• Cardiac performance: Minimum cardiac function defined as: * No history of congestive heart failure in need of medical treatment * No pre-treatment diminished left ventricular function on echocardiography (shortening fraction \[SF\] \< 25% or ejection fraction \[EF\] \< 40%) * No signs of congestive heart failure at presentation of relapse. * Participant, parent or guardian must sign and date informed consent and pediatric assent (when required), prior to the initiation of screening or study specific procedures, according to local law and legislation. Exclusion Criteria * Participants who in the opinion of the investigator may not be able to comply with the study requirements of the study, are not eligible. * Participants with Down syndrome. * Participants with Acute promyelocytic leukemia (APL) or Juvenile myelomonocytic leukemia (JMML). * Participants with isolated CNS3 disease or symptomatic CNS3 disease. * Participants with malabsorption syndrome or any other condition that precludes enteral administration of venetoclax. * Participants who are currently receiving another investigational drug (GO is not considered investigational in this study). * Participants with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known congenital bone marrow failure syndrome. * Participants with known prior allergy to any of the medications used in protocol therapy. * Participants with documented active, uncontrolled infection at the time of study entry. * No known human immunodeficiency virus (HIV) infection. * Post menarchal female participants with positive pregnancy test. * Concomitant Medications * Participants who have received strong and moderate CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort within 7 days of the start of study treatment. * Participants who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days of the start of study treatment. * Participants who have hypersensitivity to the active substance or to any of the excipients listed in summary of product characteristics (SPC). * Pregnancy or Breast-Feeding: * Participants who are pregnant or breast-feeding. * Participants of reproductive potential may not participate unless they have agreed to use a highly effective contraceptive method per clinical trials facilitation group (CTFG) guidelines for the duration of study therapy and for 6 months after the completion of all study therapy. * Male participants must use a condom during intercourse and agree not to father a child or donate sperm during therapy and for the duration of study therapy and for 4 months after the completion of all study therapy. Additional criteria to receive a gemtuzumab ozogamicin infusion: Gemtuzumab ozogamicin should not be given: * to participants with history of veno-occlusive disease (VOD)/Sinusoidal obstruction syndrome (SOS) grade 4 * to participants with history of VOD/SOS grade 3 * to participants with CD33 negative leukemic blasts (determined at local lab) Note that these participants are eligible for the study but will not be treated with gemtuzumab ozogamicin.
DRUG: Fludarabine, DRUG: Cytarabine, DRUG: Gemtuzumab Ozogamicin, DRUG: Azacitidine, DRUG: Venetoclax
Acute Myeloid Leukemia, Leukemia, Not Otherwise Specified, Leukemia, Other
Venetoclax, Gemtuzumab Ozogamicin, Fludarabine, Cytarabine, Relapsed refractory, Azacitidine
Children’s Health
First-in-Human Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, as a Single Agent in Patients With Advanced Solid Tumors and in Combination With Endocrine Therapy +/- a CDK4/6 or CDK4 Inhibitor in Patients With Advanced Solid Tumors or Advanced Breast Cancer
This is an open-label, FIH study designed to evaluate the maximum tolerated dose, recommended Phase 2 dose, safety, tolerability, PK, pharmacodynamics, and preliminary antineoplastic activity of RLY-2608, in advanced solid tumor patients with a Phosphatidylinositol-4,5-bisphosphate-3 kinase, catalytic subunit alpha (PIK3CA) mutation in blood and/or tumor per local assessment. The study will evaluate RLY-2608 as a single agent for patients with unresectable or metastatic solid tumors. It will also evaluate RLY-2608 in combination RLY-2608 + fulvestrant and in triple combination RLY-2608 + fulvestrant + CDK4/6 inhibitor (palbociclib or ribociclib) or CDK4 inhibitor (PF-07220060) for patients with HR+ HER2- locally advanced or metastatic breast cancer. The RLY-2608 single agent arm, RLY-2608 + fulvestrant combination arm, and triple combination arms will have 2 parts: a dose escalation (Part 1) and a dose expansion (Part 2).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Nisha Unni
ALL
18 Years and over
PHASE1
NCT05216432
STU-2023-1126
Key Inclusion Criteria
Patient has ECOG performance status of 0-1
One or more documented primary oncogenic PIK3CA mutation(s) in blood and/or tumor per local assessment
Other potentially oncogenic PIK3CA mutations may be considered but must be approved by the Sponsor prior to enrollment.
Part 1 \[Escalation\] - Ability to provide archived tumor tissue or be willing to undergo pretreatment tumor biopsy to assess PIK3CA status retrospectively Part 2 \[Expansion\] - Submit tumor tissue prior to study drug initiation for determination of PIK3CA mutation retrospectively.
Key Inclusion for RLY-2608 Single Agent Arm
* \[For Part 1: Escalation\]: Evaluable disease per RECIST v1.1
* \[For Part 2: Expansion\]: Measurable disease per RECIST v1.1
* Disease that is refractory to standard therapy, intolerant to standard therapy, or has declined standard therapy.
* Part 1- histologically or cytologically confirmed diagnosis of unresectable or metastatic solid tumor
* Part 2 - Unresectable or metastatic solid tumor with PIK3CA mutation(s) and one of the following tumor types:
Group 1: clear cell ovarian cancer Group 2: head and neck squamous cell carcinoma Group 3: cervical cancer Group 4: other solid tumors, excluding colorectal, clear cell ovarian, head and neck squamous cell, and cervical cancers Group 5: unresectable or metastatic solid tumors with PIK3CA double mutations In addition, the SRC (with Sponsor approval) may choose to open additional group(s) of 20 participants to study the clinical activity, safety, and PK/PD with other specified solid tumor types.
Key Inclusion for Combination Arms:
* Doublet combination arms \[Part 1 and Part 2\]: Evaluable disease per RECIST v1.1
* Triplet combination arms:
* \[Part 1 and Part 2 Dose Expansion, Group 1\]: Evaluable disease per RECIST.
* \[Part 2 Dose Expansion, Group 2\]: Measurable disease per RECIST. Bone-only lytic or lytic/blastic disease with at least 1 measurable soft-tissue component per RECIST may be eligible.
* \[For Part 1 and Part 2\]: Male or female with histologically or cytologically confirmed diagnosis of HR+, HER2- unresectable or metastatic breast cancer that is not amenable to curative therapy. Females may be postmenopausal, premenopausal, or perimenopausal. Premenopausal or perimenopausal females must have a histologically or cytologically confirmed diagnosis of HR+ HER2- locally advanced or metastatic breast cancer that is not amenable to curative therapy and must have initiated treatment with a gonadotropin-releasing hormone (GnRH) agonist at least 4 weeks prior to start of study drug with continuation of GnRH agonist for the duration of study treatment (GnRH agonist recommended for males).
* Had previous treatment for breast cancer with: \[Does not apply to triplet combination arms, Part 2 Dose Expansion, Group 2\]:
• ≤1 line of chemotherapy in the metastatic setting
• ≥1 CDK4/6 inhibitor in either the adjuvant and/or metastatic setting
• ≥1 antiestrogen therapy in either adjuvant and/or metastatic setting, including, but not limited to, selective estrogen-receptor degraders (eg, fulvestrant), selective estrogen receptor modulators (eg, tamoxifen), and aromatase inhibitors (AI) (letrozole, anastrozole, exemestane), and
• ≥1 PARP inhibitor, if appropriate, if documented germline BRCA1/2 mutation Note: Systemic local, loco-regional, or adjuvant treatment with chemotherapy and PARP inhibitors is not to be included in enumeration or previous treatment \[For double combination arm; Part 2 Dose Expansion, Group 2\]: Received prior treatment with a PI3Kα, AKT, or mTOR inhibitor and discontinued the inhibitor due to intolerance and not disease progression, where intolerance is defined as treatment discontinuation due to treatment related AE (eg. hyperglycemia, rash, diarrhea, stomatitis) other than severe hypersensitivity reaction and/or life-threatening reactions, such as anaphylaxis and Stevens-Johnson syndrome. \[For triple combination arms; Part 1 dose escalation\]: Participants who had previous treatment for breast cancer with PI3Kα, AKT, mTOR inhibitors and discontiuned due to participant/physician decision, intolerance, or disease progression will be considered. \[For triple combination arms, Part 2 Dose Expansion, Group 2\]: Participants must be intolerant to or have declined standard therapy for locally advanced or metastatic HR+/HER2- PIK3CA-mutated breast cancer. Prior endocrine therapy and CDK4/6inhibitors are allowed as follows:
• Participants must have progressed during (neo)adjuvant endocrine therapy or within12 months of completing (neo)adjuvant endocrine therapy with an AI or tamoxifen.
• If a CDK4/6 inhibitor was included as part of (neo)adjuvant therapy, disease must have recurred/progressed \>12 months after completion of the CDK4/6 inhibitor portion of (neo)adjuvant therapy Key Exclusion Criteria Prior treatment with:
• PI3Kα, AKT, or mTOR inhibitors (all arms except for doublet RLY-2608 + fulvestrant arm, Part 2, Group 2; and triplet combinations, Part 1 dose escalation).
• Immune checkpoint inhibitors.
• Triplet combinations RLY-2608 + CDK4 or CDK4/6 inhibitor + fulvestrant, Part 2 expansion, Group 2 only: i. Prior systemic chemotherapy or antibody drug conjugate for locally advanced or metastatic disease. ii. Prior CDK2, CDK4, or CDK4/6 inhibitor as treatment for locally advanced or metastatic disease. iii. Prior treatment with fulvestrant or any selective ER degrader, with the exception of patients who have received fulvestrant or any selective ER degrader as part of neoadjuvant therapy only and with treatment duration ≤6 months. Type 1 or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose ≥140 mg/dL and glycosylated hemoglobin (HbA1c) ≥7.0%. History of allergy or hypersensitivity to any components or excipients of PI3K inhibitors. For combination arms only: allergy or hypersensitivity to any components or excipients of fulvestrant, palbociclib, ribociclib, and/or PF-07220060 as appropriate for the combination. Past medical history of or ongoing ILD, or pneumonitis requiring intervention. Participants with past history of resolved Grade 1 pneumonitis may be considered, except in triple combination arms. The following cardiac criteria: * Mean resting corrected QT interval (QTc) \>460 msec * For triple combination arm with ribociclib: Mean QTcF ≥450 msec (this is what we confirmed is shown in the redacted version of the protocol. CNS metastases or primary CNS tumor that is associated with progressive neurologic symptoms
• ≤1 line of chemotherapy in the metastatic setting
• ≥1 CDK4/6 inhibitor in either the adjuvant and/or metastatic setting
• ≥1 antiestrogen therapy in either adjuvant and/or metastatic setting, including, but not limited to, selective estrogen-receptor degraders (eg, fulvestrant), selective estrogen receptor modulators (eg, tamoxifen), and aromatase inhibitors (AI) (letrozole, anastrozole, exemestane), and
• ≥1 PARP inhibitor, if appropriate, if documented germline BRCA1/2 mutation Note: Systemic local, loco-regional, or adjuvant treatment with chemotherapy and PARP inhibitors is not to be included in enumeration or previous treatment \[For double combination arm; Part 2 Dose Expansion, Group 2\]: Received prior treatment with a PI3Kα, AKT, or mTOR inhibitor and discontinued the inhibitor due to intolerance and not disease progression, where intolerance is defined as treatment discontinuation due to treatment related AE (eg. hyperglycemia, rash, diarrhea, stomatitis) other than severe hypersensitivity reaction and/or life-threatening reactions, such as anaphylaxis and Stevens-Johnson syndrome. \[For triple combination arms; Part 1 dose escalation\]: Participants who had previous treatment for breast cancer with PI3Kα, AKT, mTOR inhibitors and discontiuned due to participant/physician decision, intolerance, or disease progression will be considered. \[For triple combination arms, Part 2 Dose Expansion, Group 2\]: Participants must be intolerant to or have declined standard therapy for locally advanced or metastatic HR+/HER2- PIK3CA-mutated breast cancer. Prior endocrine therapy and CDK4/6inhibitors are allowed as follows:
• Participants must have progressed during (neo)adjuvant endocrine therapy or within12 months of completing (neo)adjuvant endocrine therapy with an AI or tamoxifen.
• If a CDK4/6 inhibitor was included as part of (neo)adjuvant therapy, disease must have recurred/progressed \>12 months after completion of the CDK4/6 inhibitor portion of (neo)adjuvant therapy Key Exclusion Criteria Prior treatment with:
• PI3Kα, AKT, or mTOR inhibitors (all arms except for doublet RLY-2608 + fulvestrant arm, Part 2, Group 2; and triplet combinations, Part 1 dose escalation).
• Immune checkpoint inhibitors.
• Triplet combinations RLY-2608 + CDK4 or CDK4/6 inhibitor + fulvestrant, Part 2 expansion, Group 2 only: i. Prior systemic chemotherapy or antibody drug conjugate for locally advanced or metastatic disease. ii. Prior CDK2, CDK4, or CDK4/6 inhibitor as treatment for locally advanced or metastatic disease. iii. Prior treatment with fulvestrant or any selective ER degrader, with the exception of patients who have received fulvestrant or any selective ER degrader as part of neoadjuvant therapy only and with treatment duration ≤6 months. Type 1 or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose ≥140 mg/dL and glycosylated hemoglobin (HbA1c) ≥7.0%. History of allergy or hypersensitivity to any components or excipients of PI3K inhibitors. For combination arms only: allergy or hypersensitivity to any components or excipients of fulvestrant, palbociclib, ribociclib, and/or PF-07220060 as appropriate for the combination. Past medical history of or ongoing ILD, or pneumonitis requiring intervention. Participants with past history of resolved Grade 1 pneumonitis may be considered, except in triple combination arms. The following cardiac criteria: * Mean resting corrected QT interval (QTc) \>460 msec * For triple combination arm with ribociclib: Mean QTcF ≥450 msec (this is what we confirmed is shown in the redacted version of the protocol. CNS metastases or primary CNS tumor that is associated with progressive neurologic symptoms
DRUG: RLY-2608, DRUG: Fulvestrant, DRUG: Palbociclib 125mg, DRUG: Ribociclib 400mg, DRUG: Ribociclib 600mg, DRUG: PF-07220060 100mg, DRUG: PF-07220060 300 mg
PIK3CA Mutation, Solid Tumor, Adult, HER2-negative Breast Cancer, Breast Cancer, Metastatic Breast Cancer, Advanced Breast Cancer, Unresectable Solid Tumor, Breast - Female, Breast - Male
UT Southwestern
Colon Adjuvant Chemotherapy Based on Evaluation of Residual Disease (CIRCULATE-US)
This Phase II/III trial will evaluate the what kind of chemotherapy to recommend to patients based on the presence or absences of circulating tumor DNA (ctDNA) after surgery for colon cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Nilesh Verma
ALL
18 Years and over
PHASE2
NCT05174169
STU-2023-0699
Inclusion Criteria:
The patient must have an ECOG performance status of 0 or 1.
Patients must have histologically/pathologically confirmed Stage IIB, IIC, or Stage III colon adenocarcinoma with R0 resection according to AJCC 8th edition criteria.
No radiographic evidence of overt metastatic disease within 45 days prior to Step 1/Study entry (CT with IV contrast or MRI imaging is acceptable and must include chest, abdomen, and pelvis).
The distal extent of the tumor must be greater than or equal to 12 cm from the anal verge on colonoscopy or above the peritoneal reflection as documented during surgery or on pathology specimen (i.e., excluding rectal adenocarcinomas warranting treatment with chemoradiation).
The patient must have had an en bloc complete gross resection of tumor (curative resection). Patients who have had a two-stage surgical procedure, to first provide a decompressive colostomy and then in a later procedure to have the definitive surgical resection, are eligible.
The resected tumor specimen and a blood specimen from patients with Stage IIB, IIC, or Stage III colon cancer must have central testing for ctDNA using the Signatera™ assay by Natera (after Step 1/Study entry and before Step2/Randomization). Patient must have sufficient tissue to meet protocol requirements. This blood specimen for the Signatera assay must be collected after surgery (and recommended at least 14 days post surgery).
Tumor must be documented as microsatellite stable or have intact mismatch repair proteins through CLIA-approved laboratory testing. Patients whose tumors are MSI-H or dMMR are excluded.
The treating investigator must deem the patient a candidate for all potential agents used in this trial (5FU, LV, oxaliplatin and irinotecan).
The interval between surgery (post-operative Day 7) and Step 1/Study entry must be no more than 60 days. NOTE: Step 1/Study Entry may occur as early as post operative Day 7, but it cannot occur beyond 60 days from the actual date of the patient's surgery.
Availability and provision of adequate surgical tumor tissue for molecular diagnostics and confirmatory profiling.
Adequate hematologic function within 28 days before Step 1/Study entry defined as follows:
* Absolute neutrophil count (ANC) must be greater than or equal to 1500/mm3;
* Participants with benign ethnic neutropenia (BEN): ANC less than 1300 mm3 are eligible.
* BEN (also known as constitutional neutropenia) is an inherited cause of mild or moderate neutropenia that is not associated with any increased risk for infections or other clinical manifestations. BEN is referred to as ethnic neutropenia because of its increased prevalence in people of African descent and other specific ethnic groups.
* Platelet count must be greater than or equal to 100,000/mm3; and
* Hemoglobin must be greater than or equal to 9 g/dL.
Adequate hepatic function within 28 days before Step 1/Study entry defined as follows:
* total bilirubin must be less than or equal to ULN (upper limit of normal) for the lab and
* alkaline phosphatase must be less than 2.5 x ULN for the lab; and
* AST and ALT must be less than 2.5 x ULN for the lab.
Adequate renal function within 28 days before Step 1/Study entry defined as serum creatinine less than or equal to 1.5 x ULN for the lab or measured or calculated creatinine clearance greater than or equal to 50 mL/min using the Cockroft-Gault formula for patients with creatinine levels greater than 1.5 x ULN for the lab.
For Women Creatinine Clearance (mL/min) = (140 - age) x weight (kg) x 0.85 72 x serum creatinine (mg/dL) For Men Creatinine Clearance (mL/min) = (140 - age) x weight (kg) 72 x serum creatinine (mg/dL) NOTE: Adjusted body weight (AdjBW) should be used for patients that have BMI greater than or equal to 28 (less than or equal to 30% above IBW).
HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
Pregnancy test (urine or serum according to institutional standard) done within 14 days before Step 1/Study entry must be negative (for women of childbearing potential only).
Patients receiving a coumarin-derivative anticoagulant must agree to weekly monitoring of INR if they are randomized to Arm 1 or Arm 3 and receive capecitabine.
Eligibility Criteria for Cohort A Arm-2 patients on Second Randomization
Patient must have developed a ctDNA +ve assay during serial monitoring.
Patient's willingness to be re-randomized affirmed.
The patient must continue to have an ECOG performance status of 0 or 1.
No radiographic evidence of overt metastatic disease.
Pregnancy test (urine or serum according to institutional standard) done within 14 days before second randomization must be negative (for women of childbearing potential only).
Adequate hematologic function within 28 days before second randomization defined as follows:
* Absolute neutrophil count (ANC) must be greater than or equal to 1500/mm3;
* Participants with benign ethnic neutropenia (BEN): ANC less than 1300 mm3 are eligible.
* BEN (also known as constitutional neutropenia) is an inherited cause of mild or moderate neutropenia that is not associated with any increased risk for infections or other clinical manifestations. BEN is referred to as ethnic neutropenia because of its increased prevalence in people of African descent and other specific ethnic groups.
* Platelet count must be greater than or equal to 100,000/mm3; and
* Hemoglobin must be greater than or equal to 9 g/dL.
Adequate hepatic function within 28 days before second randomization defined as follows:
* total bilirubin must be less than or equal to ULN (upper limit of normal) for the lab and
* alkaline phosphatase must be less than 2.5 x ULN for the lab; and
* AST and ALT must be less than 2.5 x ULN for the lab.
Adequate renal function within 28 days before second randomization defined as serum creatinine less than or equal to 1.5 x ULN for the lab or measured or calculated creatinine clearance greater than or equal to 50 mL/min using the Cockroft-Gault formula for patients with creatinine levels greater than 1.5 x ULN for the lab.
For Women Creatinine Clearance (mL/min) = (140 - age) x weight (kg) x 0.85 72 x serum creatinine (mg/dL) For Men Creatinine Clearance (mL/min) = (140 - age) x weight (kg) 72 x serum creatinine (mg/dL)
Exclusion Criteria:
Colon cancer histology other than adenocarcinoma (i.e., neuroendocrine carcinoma, sarcoma, lymphoma, squamous cell carcinoma, etc.).
Pathologic, clinical, or radiologic overt evidence of metastatic disease. This includes isolated, distant, or non-contiguous intra-abdominal metastases, even if resected.
Tumor-related bowel perforation.
History of prior invasive colon malignancy, regardless of disease-free interval.
History of bone marrow or solid organ transplantation (regardless of current immunosuppressive therapy needs). Bone grafts, skin grafts, corneal transplants and organ/tissue donation are not exclusionary.
Any prior systemic chemotherapy, targeted therapy, or immunotherapy; or radiation therapy administered as treatment for colorectal cancer (e.g., primary colon adenocarcinomas for which treatment with neoadjuvant chemotherapy and/or radiation is warranted are not permitted). EXCEPTION: one cycle of chemotherapy (regimen per treating physicians' discretion - 5-FU or capecitabine with or without oxaliplatin) is allowed but not required after consent. The optional cycle of chemotherapy should be started greater than or equal to 4 weeks from surgery and while awaiting Step 2 randomization.
Other invasive malignancy within 5 years before Step 1/Study entry. Exceptions are colonic polyps, non-melanoma skin cancer or any carcinoma-in-situ.
Synchronous primary rectal and/ or colon cancers.
Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
Sensory or motor neuropathy greater than or equal to grade 2, according to CTCAE v5.0.
Blood transfusion within two weeks before collection of blood for central ctDNA testing.
Active seizure disorder uncontrolled by medication.
Active or chronic infection requiring systemic therapy.
Known homozygous DPD (dihydropyrimidine dehydrogenase) deficiency.
Patients known to have Gilbert's Syndrome or homozygosity for UGT1A1\*28 polymorphism.
Pregnancy or lactation at the time of Step 1/Study entry.
Co-morbid illnesses or other concurrent disease that would make the patient inappropriate for entry into this study (i.e., unable to tolerate 6 months of combination chemotherapy or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens or prevent required follow-up).
Ineligibility Criteria for Cohort A Arm-2 patients on Second Randomization
Pregnancy or lactation at the time of randomization.
No longer a candidate for systemic chemotherapy (FOLFOX, CAPOX, and mFOLFIRINOX) in the opinion of the treating investigator. DEVICE: Signatera test, DRUG: mFOLFOX6 3-6 month, DRUG: CAPOX 3 month, DRUG: mFOLFIRINOX, DRUG: mFOLFOX6 6 month, DRUG: CAPOX 6 month
Stage III Colon Cancer, Colon, Rectum
ctDNA positive, ctDNA negative, Adjuvant Chemotherapy, Natera, Signatera, mFOLFOX6, Stage III, CAPOX, mFOLFIRINOX, Oxaliplatin, 5-Fluorouracil (5-FU), Capecitabine, Leucovorin, Irinotecan, Stage II
UT Southwestern; Parkland Health & Hospital System
Phase 1/2a Study of Belantamab Mafodotin in Relapsed or Refractory AL Amyloidosis
The goal of this study is to test the safety of drug, Belantamab Mafodotin, and see what effects (good and bad) it has on people who take it and have amyloidosis, and to determine the most effective dose of the drug. The study will have 2 phases (parts). The first phase of the study will test different doses of Belantamab Mafodotin. The second phase will test Belantamab Mafodotin at the dose level found to be safe and effective in phase 1
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Larry Anderson
ALL
18 Years and over
PHASE1
NCT05145816
STU-2021-0952
Inclusion Criteria:
• Participants medically diagnosed with relapsed or refractory Amyloid Light Chain Amyloidosis (AL amyloidosis) with one or more line of treatment as below:
• Must have received a proteosome inhibitor, alkylator and anti-cluster of differentiation 38 (CD38) antibody (e.g., daratumumab - for patients who were eligible to receive in newly diagnosed AL Amyloidosis) and autologous stem cell transplant (for transplant eligible candidates). OR
• Failed treatment and/or intolerant/ineligible for above agents NOTE: Patients who fail to achieve Partial Hematological Response or better after 2 cycles of induction therapy for newly diagnosed AL Amyloidosis are also eligible.
• Participant must be over 18 years of age inclusive, at the time of signing the informed consent.
• Participant and Disease Characteristics: Patient must have primary systemic AL amyloidosis, histologically confirmed at the initial diagnosis before initiation of 1st-line treatment by positive Congo red stain with green birefringence on polarized light microscopy, Or characteristic appearance by electron microscopy AND confirmatory AL amyloid typing (mass spectrometry-based proteomic analysis or immunofluorescence).
• Patient must have measurable disease within 28 days prior to registration; serum quantitative immunoglobulins (immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM), serum free kappa and lambda, and serum protein electrophoresis (SPEP) with M-protein quantification must be obtained within 14 days prior to registration.
• Measurable disease of amyloid light chain amyloidosis as defined by at least One of the following: a. Serum M-protein ≥0.5 g/dL by protein electrophoresis (routine serum protein electrophoresis and immunofixation). b. Serum free light chain ≥50 mg/L with an abnormal kappa: lambda ratio or the difference between the involved and uninvolved free light chains (dFLC) ≥50 mg/L.
• One or more organs impacted by AL Amyloidosis according to consensus guidelines below per National Comprehensive Cancer Network (NCCN)Guidelines Version 1.2016: a. Cardiac Involvement i. Mean left ventricular wall thickness on echocardiogram greater than or equal to 12 mm in the absence of hypertension or valvular heart disease, OR N-terminal fragment brain natriuretic protein (NT-pro) brain natriuretic peptide (BNP) greater than 332 ng/mL provided that patient does not have impaired renal function (as defined by calculated creatinine clearance less than 25 mL/min) within 14 days prior to registration, OR prior cardiac biopsy (at time of diagnosis) showing amyloid deposition with past documented or presently noted clinical symptoms and signs supportive of a diagnosis of heart failure in the absence of an alternative explanation for heart failure. b. Non-Cardiac Organ Involvement i. Kidney: albuminuria greater than or equal to 500 mg per day on a 24-hour urine specimen within 35 days prior to registration, OR prior kidney biopsy (at the time of diagnosis) showing amyloid deposition. ii. Liver: hepatomegaly (total liver span \> 15 cm) as demonstrated by computed tomography (CT) or magnetic resonance imaging (MRI) within 35 days prior to registration OR alkaline phosphatase (ALP) greater than 1.5 times the institutional upper limit of normal within 14 days prior to registration, OR prior liver biopsy (at the time of diagnosis) showing amyloid deposition. iii. Gastrointestinal tract: direct biopsy verification with symptoms. iv. Lung: biopsy verifications with symptoms and interstitial radiographic pattern. v. Soft tissue: tongue enlargement, clinical, arthropathy, claudication, presumed vascular amyloid, skin involvement, carpal tunnel syndrome, myopathy by biopsy or pseudohypertrophy.
• Patients must have completed other systemic therapy or investigational drug ≥ 28 days or five half-lives prior to registration, surgery (other than biopsies) ≥ 28 days prior to registration, and any autologous stem cell transplant (ASCT) ≥ 100 days prior to registration.
• Patients must have a complete medical history and physical exam within 14 days prior to registration.
• New York Heart Association (NYHA) Class 1 - 3a which has been clinically stable for 56 days before registration
• Eastern Cooperative Oncology Group (ECOG) performance score 0, 1 or 2
• Left ventricular ejection fraction (LVEF) by echocardiogram (ECHO) \> 35% within 28 days prior to registration.
• Adequate organ system functions within 14 days of registration as defined by the laboratory assessments below: a) Hematologic i) Absolute neutrophil count (ANC): ≥1.0 × 10(9)/ L \* ii) Hemoglobin: ≥8.0 g/dL \* iii) Platelets: ≥50 × 10(9)/L \* b) Hepatic i) Total bilirubin: ≤1.5 × upper limit of normal (ULN); (Isolated bilirubin ≥1.5 × ULN is acceptable if bilirubin is fractionated, and direct bilirubin is \<35%) ii) Alanine aminotransferase (ALT): ≤2.5 × ULN c) Renal i) Estimated glomerular rate (eGFRª): ≥30 mL/min/1.73 m2 Note: Laboratory results obtained during Screening should be used to determine eligibility criteria. In situations where laboratory results are outside the permitted range, the investigator may re-test the participant and the subsequent within range screening result may be used to confirm eligibility. \* Without growth factor or cell transfusion support for the past 14 days prior to testing, excluding erythropoietin. ª As calculated by Modified Diet in Renal Disease (MDRD) formula (Appendix 4 in Protocol)
• Females of childbearing potential: These participants must have a negative baseline pregnancy test using serum or urine within 14 days prior to starting therapy and a confirmatory negative serum pregnancy test with a sensitivity of at least 50 mIU/mL within 72 hours prior to registration; females of childbearing potential must also agree: (1) to have a pregnancy test prior to the start of each treatment cycle and (2) to either commit to continued abstinence from heterosexual intercourse or to use effective contraception while receiving study drug and for at least 4 months after receiving the last dose of study drug; females are considered to be of childbearing potential if they have had menses at any time in the preceding 24 consecutive months; in addition to routine contraceptive methods, effective contraception also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, she is responsible for beginning contraceptive measures.
• Is a woman of child bearing potential (WOCBP) and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), preferably with low user dependency (as described in Appendix 9), during the intervention period and for at least 4 months after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
• A WOCBP must have a negative serum pregnancy test (as required by local regulations) within 72 hours before the first dose of study intervention.
• The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with a nearly undetected pregnancy.
• Non-childbearing potential is defined as follows (by other than medical reasons): i. ≥45 years of age and has not had menses for \>1 year. ii. Patients who have been amenorrhoeic for \<2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation. iii. Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure. 14\. Male participants are eligible to participate if they agree to the following during the intervention period and for 6 months after the last dose of study treatment to allow for clearance of any altered sperm:
• Refrain from donating sperm Plus, either:
• be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent Or
• agree to use a barrier method of birth control (e.g., male condom), even if they have undergone a successful vasectomy, and female partner to use an additional highly effective contraceptive method with a failure rate of \<1% per year as when having sexual intercourse with a woman of childbearing potential (including pregnant females). 15\. Patients with Human Immunodeficiency Virus (HIV) infection are eligible if: a. patients without a history of Acquired Immune Deficiency Syndrome (AIDS)-defining opportunistic infections b. patients with a history of AIDS-defining opportunistic infection may be eligible if they have not had an opportunistic infection within past 12 months. c. Patients on active anti-retroviral therapy are eligible as long as anti-retroviral therapy is established for at least four weeks and have HIV viral load less than 400 copies/ml prior to enrollment. 16\. Patients with chronic Hepatitis B Virus (HBV) infection or chronic Hepatitis C Virus (HCV) infection or virologically suppressed on HCV treatment are eligible if:
• Hepatitis B surface antigen (HBsAg)-negative, anti-Hemoglobin C (HBc)-positive patients are at lower risk of HBV reactivation compared with HBsAg-positive patients, risk of HBV reactivation should be considered in all patients and if patients can be on anti-HBV prophylaxis prior to initiation of anti-cancer therapy.
• Patients with chronic HBV infection with active disease who meet the criteria for anti HBV therapy should be on a suppressive antiviral therapy prior to initiation of cancer therapy.
• Patients actively on treatment for HCV should have HCV below the limit of quantification before initiation of anti-cancer therapy.
• Patients who are HCV antibody (Ab) positive but HCV Ribonucleic Acid (RNA) negative due to prior treatment or natural resolution of infection are eligible.
Exclusion Criteria:
• Patients previously treated for active symptomatic multiple myeloma.
• Any corneal disease except for mild epithelial punctate keratopathy.
• Patients with known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to belantamab mafodotin or drugs chemically related to belantamab mafodotin, or any of the components of the study treatment.
• Patients eligible for autologous stem cell transplantation (ASCT).
• Evidence of significant cardiovascular condition as specified below:
• N-terminal-prohormone of brain natriuretic peptide (NT-proBNP) ≥ 8500ng/L within 14 days of registration.
• New York Heart Association (NYHA) classification IIIB (3b) through IV (4) heart failure
• Heart failure that in the opinion of the investigator is on the basis of ischemic heart disease (e.g., prior myocardial infarction with documented history of cardiac enzyme elevation and electrocardiogram (ECG) changes) or uncorrected valvular disease and not primarily due to AL amyloid cardiomyopathy
• Unstable heart failure defined as emergency hospitalization for worsening, or decompensated heart failure, or syncopal episode within 1 month of screening
• Subjects with a history of sustained ventricular tachycardia or aborted ventricular fibrillation or with a history of atrioventricular nodal or sinoatrial (SA) nodal dysfunction for which a pacemaker/implantable cardioverter-defibrillator (ICD) is indicated but not placed (Subjects who do have a pacemaker/ICD are allowed on study)
• Interval from the Q wave on the ECG to point T using Fredericia's formula (QTcF) \> 500 msec. Subjects who have a pacemaker may be included regardless of calculated QTc interval
• Symptomatic, clinically significant autonomic neuropathy which the Investigator feels will preclude administration of study treatment
• Acute coronary syndrome, or any form of coronary revascularization procedure including coronary artery bypass grafting (CABG), within 6 months of screening
• Prior solid organ transplant, or anticipated to undergo solid organ transplantation, or requiring left ventricular assist device (LVAD) implantation, during the course of the study
• Stroke within 6 months of screening, or transient ischemic attack (TIA) within 3 months of screening
• Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Mobitz Type II) or 3rd degree atrioventricular (AV) block
• History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within three (3) months of Screening
• Uncontrolled hypertension
• Prior history of malignancy with the exception of the following: adequately treated basal cell or squamous cell skin cancer, curatively treated non-melanoma skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for at least two years.
• Presence of any comorbid or uncontrolled medical condition (e.g. uncontrolled hypertension) - defined as defined as an average SBP ≥ 160mm Hg or diastolic ≥ 100mm Hg despite optimal treatment) at screening, which in the opinion of the investigator would increase the potential risk to the subject.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• Received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 4 weeks or five half-lives, whichever is shorter, before Cycle 1 Day 1.
• Participant must not use contact lenses while participating in this study.
• Participant must not have had major surgery ≤ 4 weeks prior to initiating study treatment.
• Participant must not have any evidence of active mucosal or internal bleeding.
• Participant must not have any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including lab abnormalities) that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures.
• Participants must not be pregnant or lactating.
• Participant must not be simultaneously enrolled in any interventional clinical trial.
• Participant must not have an active infection requiring treatment.
• Participant must not have current unstable liver or biliary disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Note: Stable non-cirrhotic chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if otherwise meets entry criteria.
DRUG: Belantamab mafodotin 2.5 mg/kg (8 weeks), DRUG: Belantamab mafodotin 1.9 mg/kg (8 weeks), DRUG: Belantamab mafodotin 1.4 mg/kg (12 weeks), DRUG: Belantamab mafodotin 1.9 mg/kg (12 weeks), DRUG: Belantamab mafodotin every 8 weeks or 12 weeks as determined by Part 1 recommended dosages, DRUG: Belantamab mafodotin 1.0 mg/kg (12 weeks)
AL Amyloidosis, Amyloidosis, Multiple Myeloma
UT Southwestern