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Enasidenib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia Patients With an IDH2 Mutation
This trial studies the side effects of enasidenib and to see how well it works in treating patients with acute myeloid leukemia that has come back after treatment (relapsed) or has been difficult to treat with chemotherapy (refractory). Patients must also have a specific genetic change, also called a mutation, in a protein called IDH2. Enasidenib may stop the growth of cancer cells by blocking the mutated IDH2 protein, which is needed for cell growth.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kathleen Ludwig
114894
All
24 Months to 18 Years old
Phase 2
NCT04203316
STU-2020-0395
Inclusion Criteria:
• Patient must have AML with an IDH2 mutation identified from a peripheral blood or bone marrow sample at the time of diagnosis and/or relapsed/refractory disease
• Patient must have bone marrow assessment (aspiration or biopsy) with > 5% leukemic blasts by morphology and/or flow cytometry in at least one of the following clinical scenarios:
• Second or greater relapse after chemotherapy or hematopoietic stem cell transplant (HSCT)
• Refractory after >= 2 attempts at induction therapy
• Relapsed patients
• Must not have received prior re-induction therapy for this relapse
• Each block of chemotherapy (i.e., cytarabine, daunorubicin and etoposide [ADE], cytarabine and mitoxantrone [MA]) is a separate re-induction attempt
• Donor lymphocyte infusion (DLI) is considered a re-induction attempt
• Refractory patients
• Each attempt at induction therapy may include up to two chemotherapy courses
• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age. 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 the performance score
• Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
• Evaluation of cerebrospinal fluid (CSF) is only required if there is a clinical suspicion of central nervous system (CNS) involvement by leukemia during eligibility screening. Should a patient be found to have CNS2 or CNS3 status by CSF prior to eligibility screening, patient may receive intrathecal chemotherapy > 72 hours prior to starting study drug. CNS1 status must be established before starting study drug
• Patients 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 enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive. The duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
• >= 14 days must have elapsed after the completion of other cytotoxic therapy with the exception of hydroxyurea. Additionally, patients must have fully recovered from all acute toxic effects of prior therapy. NOTE: Cytoreduction with hydroxyurea must be discontinued >= 24 hours prior to the start of protocol therapy
• Intrathecal chemotherapy must be completed >= 72 hours prior to the start of the first cycle of treatment
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent. The duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• 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. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair and the study research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
• Stem cell Infusions (with or without total body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including DLI or boost infusion:
• >= 60 days after infusion for bone marrow or stem cell transplant and
• >= 4 weeks after infusion for any stem cell infusion including DLI or boost infusion
• There must be no evidence of graft versus host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular Therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
• XRT/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-metaiodobenzylguanidine [MIBG]): >= 42 days after systemically administered radiopharmaceutical therapy
• Study-specific limitations on prior therapy: small molecule investigational agents: >= 14 days or > 5 half-lives must have elapsed from the last dose of the agent, whichever is greater
• Platelet count >= 20,000/mm^3 (may receive platelet transfusions). These patients must not be known to be refractory to red cell or platelet transfusion
• Hemoglobin >= 8.0 g/dL at baseline (may receive red blood cell [RBC] transfusions)
• Creatinine clearance or radioisotope glomerular filtration rate [GFR] >= 70 ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• Age: Maximum serum creatinine (mg/dL)
• 2 to < 6 years: 0.8 (male and female)
• 6 to < 10 years: 1 (male and female)
• 10 to < 13 years: 1.2 (male and female)
• 13 to < 16 years: 1.5 (male); 1.4 (female
• >= 16 years: 1.7 (male); 1.4 (female)
• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 225 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L
• Serum albumin >= 2 g/dL
• Left ventricular ejection fraction of >= 50% by echocardiogram
• Regulatory Requirements
• All patients and/or their parents or legal authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
• AML associated with Down syndrome or t(15;17) is not eligible for study
• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study therapy and for 4 months after the last dose of enasidenib. Abstinence is an acceptable method of birth control. It is not known if enasidenib is present in breast milk. Breastfeeding is not recommended during therapy or for at least 30 days after the last dose of enasidenib
• Concomitant Medications:
• Corticosteroids: Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid. The use of corticosteroids to manage the side effect of IDH inhibitor-associated differentiation syndrome (IDH-DS), is permitted on study
• Investigational drugs: Patients who are currently receiving another investigational drug are not eligible
• Anti-cancer agents: Patients who are currently receiving other anti-cancer agents are not eligible (except leukemia patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy; the use of hydroxyurea to manage the side effect of IDH-DS, is permitted on study)
• Anti-GVHD agents post-transplant: Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
• Patients must be able to swallow intact tablets whole.
• Patients with known hypersensitivity to any of the components of enasidenib are not eligible.
• Patients with prior exposure to enasidenib or another IDH2 inhibitor are not eligible.
• Patients taking the following drugs will be excluded from study entry unless these drugs are discontinued or patients are transferred to a medically acceptable alternative > 5 half-lives before the first dose of enasidenib.
• Drugs with a narrow therapeutic range that are sensitive substrates of the following cytochrome P450 (CYP) enzymes: CYP2C8 (e.g. paclitaxel), 2C9 (e.g. phenytoin and warfarin), 2C19 (e.g. s-mephenytoin), 2D6 (e.g. thioridazine), and 1A2 (e.g. theophylline and tizanidine).
• Breast cancer resistant protein (BCRP) transporter-sensitive substrate rosuvastatin
• Patients with the following leukemia complications are not eligible for this trial:
• No intrathecal chemotherapy is permitted on study. Prior to study enrollment, cerebrospinal fluid (CSF) evaluation is only required if there is a clinical suspicion for CNS leukemia. Clinical signs of CNS leukemia (such as facial nerve palsy, brain/eye involvement or hypothalamic syndrome) are not eligible for this trial
• Immediately life-threatening, severe complications of leukemia including uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation
• Infection: Patients who have an uncontrolled infection or patients with known human immunodeficiency virus (HIV) or active hepatitis B or C are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• 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
Drug: Enasidenib, Drug: Enasidenib Mesylate
Refractory Acute Myeloid Leukemia, Recurrent Acute Myeloid Leukemia
Children’s Health
Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101)
To evaluate the safety and tolerability of sotorasib administered in investigational regimens in adult participants with KRAS p.G12C mutant advanced solid tumors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Syed Kazmi
177531
All
18 Years to 100 Years old
Phase 1/Phase 2
NCT04185883
STU-2020-0332
Inclusion Criteria:
• Men or women greater than or equal to 18 years old.
• Pathologically documented, locally-advanced or metastatic malignancy with, KRAS p.G12C mutation identified through molecular testing performed according to in-country requirements. In the United States, this test must be performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.
Exclusion Criteria:
• Primary brain tumor.
• Spinal cord compression, or untreated, or symptomatic, or active brain metastases, or leptomeningeal disease from non-brain tumors.
• Myocardial infarction within 6 months of study day 1.
• Gastrointestinal (GI) tract disease causing the inability to take oral medication.
Drug: Sotorasib, Drug: AMG 404, Drug: trametinib, Drug: RMC-4630, Drug: afatinib, Drug: pembrolizumab, Drug: panitumumab, Drug: carboplatin, pemetrexed, docetaxel, paclitaxel, Drug: atezolizumab, Drug: everolimus, Drug: palbociclib, Drug: MVASI® (bevacizumab-awwb), Drug: TNO155, Drug: FOLFIRI, Drug: FOLFOX, Drug: BI 1701963
Advanced Solid Tumors, Kirsten Rat Sarcoma (KRAS) pG12C Mutation
UT Southwestern
Osimertinib With or Without Bevacizumab as Initial Treatment for Patients With EGFR-Mutant Lung Cancer
This phase III trial compares the effect of bevacizumab and osimertinib combination vs. osimertinib alone for the treatment of non-small cell lung cancer that has spread outside of the lungs (stage IIIB-IV) and has a change (mutation) in a gene called EGFR. The EGFR protein is involved in cell signaling pathways that control cell division and survival. Sometimes, mutations in the EGFR gene cause EGFR proteins to be made in higher than normal amounts on some types of cancer cells. This causes cancer cells to divide more rapidly. Osimertinib may stop the growth of tumor cells by blocking EGFR that is needed for cell growth in this type of cancer. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Giving osimertinib with bevacizumab may control cancer for longer and help patients live longer as compared to osimertinib alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Sheena Bhalla
203321
All
18 Years and over
Phase 3
NCT04181060
STU-2022-0495
Inclusion Criteria:
• Patient must have a pathologically-confirmed diagnosis of non-squamous, non-small cell lung cancer (NSCLC)
• Patient must have advanced disease, defined as - either stage IV disease, stage IIIB disease not amenable to definitive multi-modality therapy, or recurrent disease after a prior diagnosis of stage I-III disease. All staging is via the American Joint Committee on Cancer (AJCC)/International Association for the Study of Lung Cancer (IASLC) 8th edition staging criteria
• Patient must have somatic activating sensitizing mutation in EGFR (e.g. but not limited to Exon 19 deletion, L858R, E709X, G719X, exon 19 insertions, L861Q, S768I). Patients with non-sensitizing mutations in EGFR (EGFR exon 20 insertions) are not eligible. Test results originating from a Clinical Laboratory Improvement Act (CLIA)-certified or similarly accredited laboratory are acceptable; no specific assay is mandated. Plasma, cytology, or tumor tissue can be utilized for mutation testing
• Patient must not have received any prior treatment with an EGFR TKI or with an anti-VEGF agent
• Patients that have received prior radiation therapy are eligible. Radiation (limited field stereotactic radiation or conventional radiation) must have been completed at least one week prior to study drug initiation and more extensive field radiation (i.e., whole-brain radiotherapy [WBRT]) must have been completed at least two weeks prior to drug initiation
• Patient must not have any risk factors for anti-VEGF administration, specifically, hemoptysis, active cardiovascular disease, uncontrolled hypertension, significant proteinuria (screening urinalysis > 300 mg/dl) and tumor invading major blood vessels
• Patient must have measurable disease. Baseline measurements of sites of disease must be obtained within 4 weeks prior to study registration. If a potential target lesion is previously irradiated without subsequent growth and/or is radiated after the imaging from which baseline measurements are obtained, they cannot be included as target lesions, and additional target lesions are required to meet criteria for measurable disease
• Patient must not have had any prior systemic treatment for metastatic disease
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used
• All females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy
• A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
• Patient of childbearing potential and sexually active males must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for 2 weeks prior to the start of treatment, while on study treatment, and for
• 6 weeks after the last dose of protocol treatment for female patients on the osimertinib (AZD9291) alone arm
• 4 months after the last dose of protocol treatment for male patients on osimertinib (AZD9291) alone arm
• 6 months after the last dose of protocol treatment for all patients on osimertinib (AZD9291) plus bevacizumab combination arm
• NOTE: Female patients should also not breastfeed while on treatment and for 6 months after the last dose bevacizumab
• Leukocytes >= 3,000/mcL (obtained =< 14 days prior to registration)
• Absolute neutrophil count >= 1,500/mcL (obtained =< 14 days prior to registration)
• Platelets >= 100,000/mcL (obtained =< 14 days prior to registration)
• Hemoglobin >= 9 g/dL (obtained =< 14 days prior to registration)
• Total bilirubin and creatinine =< 1.5 x institutional upper limit of normal (ULN) (obtained =< 14 days prior to registration)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained =< 14 days prior to registration)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• 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 neurologically stable without glucocorticoid therapy after the stated washout period from radiation therapy (RT) or surgery provided the metastatic lesions are non-hemorrhagic
• Patients with untreated brain metastases or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required provided the metastatic lesions are non-hemorrhagic and are neurologically stable without glucocorticoid therapy
• 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 known history or current symptoms of cardiac disease, 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
• Patient must have the ability to understand and the willingness to sign a written informed consent document and comply with study requirements
• Patient must not have had treatment with any investigational drug within five half-lives or 3 months (whichever is greater), prior to study initiation
• Patient must not be currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of CYP3A4. For any patient currently receiving such inducers of CYP3A4, they must discontinue use prior to first dose of study treatment. All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4
• Patient must not have any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of registration, with the exception of alopecia and grade 2 prior platinum-therapy-related neuropathy
• Patient must not have any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it challenging for the patient to participate in the study. Screening for chronic conditions is not required
• Patient must not have refractory nausea and vomiting, chronic gastrointestinal diseases, the inability to swallow the osimertinib tablets or previous significant bowel resection that would preclude adequate absorption of osimertinib
• Patient must not have a medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
• Patient must not have a history of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib
• Patient must not have mean resting corrected QT interval (QTc) > 470 msec obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived QTc value (using Bazett's correction)
• Patient must not have any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second-degree heart block
• Patient must not have any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, electrolyte abnormalities (including: potassium < lower limit of normal [LLN]; magnesium < LLN; calcium < LLN), congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval and cause torsades de pointes
Biological: Bevacizumab, Procedure: Biospecimen Collection, Procedure: Computed Tomography, Procedure: Echocardiography, Procedure: Magnetic Resonance Imaging, Procedure: Multigated Acquisition Scan, Drug: Osimertinib
Metastatic Lung Non-Squamous Non-Small Cell Carcinoma, Recurrent Lung Non-Squamous Non-Small Cell Carcinoma, Stage IIIB Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8, Advanced Lung Non-Squamous Non-Small Cell Carcinoma
UT Southwestern; Parkland Health & Hospital System
A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma
This phase III trial compares the effect of selumetinib versus the standard of care treatment with carboplatin and vincristine (CV) in treating patients with newly diagnosed or previously untreated low-grade glioma (LGG) that does not have a genetic abnormality called BRAFV600E mutation and is not associated with systemic neurofibromatosis type 1. Selumetinib works by blocking some of the enzymes needed for cell growth and may kill tumor cells. Carboplatin and vincristine are chemotherapy drugs that work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. The overall goal of this study is to see if selumetinib works just as well as the standard treatment of CV for patients with LGG. Another goal of this study is to compare the effects of selumetinib versus CV in subjects with LGG to find out which is better. Additionally, this trial will also examine if treatment with selumetinib improves the quality of life for subjects who take it.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Daniel Bowers
10760
All
2 Years to 21 Years old
Phase 3
NCT04166409
STU-2020-0013
Inclusion Criteria:
• Patients must be >= 2 years and =< 21 years at the time of enrollment
• Patients must have a body surface area (BSA) of >= 0.5 m^2 at enrollment
• Patients must have non-neurofibromatosis type 1 (non-NF1) low-grade glioma (LGG) without a BRAFV600E mutation as confirmed by Rapid Central Pathology and Molecular Screening Reviews performed on APEC14B1 (NCT02402244) and that has not been treated with any modality besides surgery. Note: Patients may be newly-diagnosed OR previously diagnosed, and there is no required time frame between biopsy/surgery and treatment initiation.
• Patients with residual tumor after resection or progressive tumor after initial diagnosis (with or without surgery) who have not received treatment (chemotherapy and/or radiation) are eligible
• Patients must have two-dimensional measurable tumor >= 1 cm^2 to be eligible
• Eligible histologies will include all tumors considered low-grade glioma or low-grade astrocytoma (World Health Organization [WHO] grade I and II) by 5th edition WHO classification of central nervous system (CNS) tumors with the exception of subependymal giant cell astrocytoma
• Patients with metastatic disease or multiple independent primary LGG are eligible
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR a serum creatinine based on age/gender as follows (performed within 7 days prior to enrollment):
• Age: Maximum Serum Creatinine (mg/dL)
• 2 to < 6 years: 0.8 mg/dL (male); 0.8 mg/dL (female)
• 6 to < 10 years: 1 mg/dL (male); 1 mg/dL (female)
• 10 to < 13 years: 1.2 mg/dL (male); 1.2 mg/dL (female)
• 13 to < 16 years: 1.5 mg/dL (male); 1.4 mg/dL (female)
• >= 16 years: 1.7 mg/dL (male); 1.4 mg/dL (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (performed within 7 days prior to enrollment) (children with a diagnosis of Gilbert's syndrome will be allowed on study regardless of their total and indirect [unconjugated] bilirubin levels as long as their direct [conjugated] bilirubin is < 3.1 mg/dL)
• Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (performed within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L
• Albumin >= 2 g/dL (performed within 7 days prior to enrollment)
• Left ventricular ejection fraction (LVEF) >= 53% (or institutional normal; if the LVEF result is given as a range of values, then the upper value of the range will be used) by echocardiogram (performed within 4 weeks prior to enrollment)
• Corrected QT (QTc) interval =< 450 msec by electrocardiography (EKG) (performed within 4 weeks prior to enrollment)
• Absolute neutrophil count >= 1,000/uL (unsupported) (performed within 7 days prior to enrollment)
• Platelets >= 100,000/uL (unsupported) (performed within 7 days prior to enrollment)
• Hemoglobin >= 8 g/dL (may be supported) (performed within 7 days prior to enrollment)
• Patients with a known seizure disorder should be stable and should not have experienced a significant increase in seizure frequency within 2 weeks prior to enrollment
• Patients 2-17 years of age must have a blood pressure that is =< 95th percentile for age, height, and gender at the time of enrollment (with or without the use of anti-hypertensive medications)
• Patients >= 18 years of age must have a blood pressure =< 130/80 mmHg at the time of enrollment (with or without the use of anti-hypertensive medications)
• Note for patients of all ages: Adequate blood pressure can be achieved using medication for the treatment of hypertension
• All patients must have ophthalmology toxicity assessments performed within 4 weeks prior to enrollment
• For all patients, a magnetic resonance imaging (MRI) of the brain (with orbital cuts for optic pathway tumors) and/or spine (depending on the site(s) of primary disease) with and without contrast must be performed within 4 weeks prior to enrollment
• 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
• Patients must have the ability to swallow whole capsules
• All patients have signed an appropriate consent form and Health Insurance Portability and Accountability Act (HIPAA) authorization form (if applicable)
• All patients and/or their parents or legal guardians must sign a written informed consent
• All patients have been consented and enrolled on APEC14B1 (NCT02402244) followed by enrollment on the ACNS1833 Pre-Enrollment Eligibility Screening (Step 0) on the same day to complete the Rapid Central Review
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
• Patients must not have received any prior tumor-directed therapy including chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant. Prior surgical intervention is permitted
• Patients with a concurrent malignancy or history of treatment (other than surgery) for another tumor within the last year are ineligible
• Patients with diffuse intrinsic pontine tumors as seen on MRI (> 2/3 of pons involvement on imaging) are not eligible even if biopsy reveals grade I/II histology
• Patients may not be receiving any other investigational agents
• Patients with any serious medical or psychiatric illness/condition, including substance use disorders or ophthalmological conditions, likely in the judgment of the investigator to interfere or limit compliance with study requirements/treatment
• Patients who, in the opinion of the investigator, are not able to comply with the study procedures are not eligible
• Female patients who are pregnant are not eligible 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 are not eligible
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for 12 weeks after stopping study therapy are not eligible.
• Note: Women of child-bearing potential and males with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) should use effective methods of contraception for the duration of the study and for 12 weeks after stopping study therapy to avoid pregnancy and/or potential adverse effects on the developing embryo
• Known genetic disorder that increases risk for coronary artery disease. Note: The presence of dyslipidemia in a family with a history of myocardial infarction is not in itself an exclusion unless there is a known genetic disorder documented
• Symptomatic heart failure
• New York Health Association (NYHA) class II-IV prior or current cardiomyopathy
• Severe valvular heart disease
• History of atrial fibrillation
• Current or past history of central serous retinopathy
• Current or past history of retinal vein occlusion or retinal detachment
• Patients with uncontrolled glaucoma
• If checking pressure is clinically indicated, patients with intraocular pressure (IOP) > 22 mmHg or ULN adjusted by age are not eligible
• Supplementation with vitamin E greater than 100% of the daily recommended dose. Any multivitamin containing vitamin E must be stopped prior to study enrollment even if less than 100% of the daily recommended dosing for vitamin E
• Surgery within 2 weeks prior to enrollment, with the exception of surgical biopsy, placement of a vascular access device or cerebral spinal fluid (CSF) diverting procedure such as endoscopic third ventriculostomy (ETV) and ventriculoperitoneal (VP) shunt.
• Note: Patients must have healed from any prior surgery
• Patients who have an uncontrolled infection are not eligible
Procedure: Biospecimen Collection, Drug: Carboplatin, Procedure: Magnetic Resonance Imaging, Other: Quality-of-Life Assessment, Other: Questionnaire Administration, Drug: Selumetinib Sulfate, Drug: Vincristine Sulfate
Low Grade Glioma, Low Grade Astrocytoma, Metastatic Low Grade Astrocytoma, Metastatic Low Grade Glioma
Children’s Health
Safety, Tolerability and Pharmacokinetics of a Monoclonal Antibody Specific to B-and T-Lymphocyte Attenuator (BTLA) as Monotherapy and in Combination With an Anti-PD1 Monoclonal Antibody for Injection in Subjects With Advanced Malignancies
The primary objective is to assess the safety and tolerability of TAB004 as monotherapy and in combination with toripalimab in subjects with selected advanced solid malignancies, including lymphoma, and to evaluate the recommended Phase 2 dose. The secondary objectives are to: 1) describe the pharmacokinetic (PK) profile of TAB004 monotherapy and in combination with toripalimab and to describe the PK profile of toripalimab when administered with TAB004, 2) evaluate antitumor activity of TAB004 monotherapy and in combination with toripalimab; and 3) determine the immunogenicity of TAB004 monotherapy and in combination with toripalimab and to determine the immunogenicity of toripalimab when administered with TAB004. The exploratory objectives are to: 1) evaluate pharmacodynamic effects of TAB004 on its target receptor BTLA, as well as effects on the immune system; 2) evaluate biomarkers that may correlate with activity of TAB004 as monotherapy and in combination with toripalimab; 3) evaluate the utility of BTLA ligand, herpesvirus-entry mediator (HVEM), and additional exploratory biomarkers that could aid in selection of appropriate subjects for TAB004 monotherapy and in combination with toripalimab.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Farrukh Awan
180091
All
18 Years and over
Phase 1
NCT04137900
STU-2020-0419
Inclusion Criteria:
• 1. Able to understand and willing to sign the Informed Consent Form;
• 2. Male or female ≥ 18 years;
• 3. Subjects with histologically or cytologically confirmed advanced unresectable or metastatic solid tumor, including lymphoma that have progressed following prior treatment. In Part A, subjects must have received, or be ineligible for or intolerant of all available approved or standard therapies known to confer clinical benefit including immunotherapy, or for whom no standard therapy exists; in Part B, subjects with advanced or metastatic solid tumors, including but not limited to lymphoma, melanoma, NSCLC, or other tumors with agreement of the Sponsor, who must have received at least one line of therapy for advanced or metastatic disease, but are not required to have received all standard therapies known to confer clinical benefit; In Part C, subjects must have received at least one line of therapy for advanced or metastatic disease but are not required to have received all standard therapies known to confer clinical benefit; In Part D, subjects with advanced or metastatic solid tumors that may include but not limited to lymphoma, melanoma, NSCLC, RCC or UC who must have received at least one line of therapy for advanced or metastatic disease, but are not required to have received all standard therapies known to confer clinical benefit.
• 4. Measurable disease per RECISTv1.1 and iRECIST, or RECIL 2017 for lymphoma
• 5. ECOG performance status of 0 or 1 with life expectancy of 3 months in the opinion of the investigator.
• 6. Adequate organ and marrow function, as defined below:
• Hemoglobin 8.0 g/dL within first 2 weeks prior to first dose of TAB004 (are not requiring a transfusion within 14 days prior to dosing)
• Absolute neutrophil count (ANC) 1.0 x 109 /L (1,000 /mm3)
• Absolute lymphocyte count ≥ 0.6 x 109/L (600/mm3)
• Platelet count 75 x 109 /L (75,000 /mm3), and not requiring platelet transfusions within the 5 days prior to dosing
• Total bilirubin ≤ 1.5 x ULN except subjects with documented Gilbert's syndrome who must have a baseline total bilirubin ≤ 3.0 mg/dL
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN; for subjects with hepatic metastases, ALT and AST ≤ 5 x ULN
• Serum creatinine ≤ 1.5 x ULN OR calculated creatinine clearance (CrCl) or 24 hour urine CrCl ≥ 40 mL/minute Cockcroft-Gault formula will be used to calculate CrCl. 24-hour urine CrCl will be derived using the measured creatinine clearance formula
• International normalized ratio (INR) ≤ 2.0 and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN; applies only to subjects who do not receive therapeutic anticoagulation; subjects receiving therapeutic anticoagulation (such as low-molecular weight heparin or warfarin) should be on a stable dose
• 7. Willingness to provide consent for biopsy samples (In Part A, fresh pre-treatment biopsies will be requested from subjects with safely accessible lesions. For subjects who cannot provide a fresh pre-treatment biopsy, request for the most recent accessible archival specimen will be required. In Part B, C and D, fresh pre-treatment biopsies will be required from subjects with safely accessible lesions. The most recent archival specimens will also be requested).
• 8. Females of childbearing potential who are sexually active with a nonsterilized male partner must use effective contraception from time of screening, and must agree to continue using such precautions for 90 days after the final dose of TAB004 or toripalimab; cessation of birth control after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control.
• 9. Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as at least 12 months with no menses confirmed by follicle-stimulating hormone [FSH] levels. FSH testing will be conducted at the Screening visit to confirm post-menopausal status).
• 10. Subjects must use effective contraception. Nonsterilized males who are sexually active with a female partner of childbearing potential must use effective contraception from Day 1 and for 90 days after receipt of the final dose of TAB004 or toripalimab.
Exclusion Criteria:
• 1. Concurrent enrollment in another clinical study, unless it is an observational (non interventional) clinical study or the follow-up period of an interventional study.
• 2. Any concurrent anti-cancer therapy, such as but not limited to chemotherapy, targeted therapy, radiotherapy, immunotherapy, or biologic therapy. Radiation treatment for palliative intent is allowed provided that lesions other than those receiving radiation are available to measure response. Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for type 2 diabetes and hormone replacement therapy) is acceptable. Note: Local treatment of isolated lesions for palliative intent is acceptable (e.g., by local surgery or radiotherapy).
• 3. Receipt of any investigational anticancer therapy within 28 days prior to the first dose of TAB004 or, provided documentable, 5 half lives whichever is shorter, except for lymphoma in which the exclusionary period is 2 weeks for immune checkpoint inhibitors only.
• 4. Current or prior use of immunosuppressive medication within 2 weeks prior to the first dose of TAB004, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids not to exceed 10 mg/day of prednisone or equivalent.
• 5. Prior exposure to anti-BTLA, or anti-HVEM antibodies for subjects enrolled into Part A and B only; prior treatment with anti-PD-1 or anti-PDL-1is allowed,including toripalimab for all subjects.
• 6. Prior allogeneic bone marrow transplantation or prior solid organ transplantation.
• 7. Subjects with another malignancy, or history or other malignancy within 3 years that is not expected to relapse. Subjects with non-melanomatous skin cancer or cervical cancer that has been curatively surgically resected are eligible.
• 8. Major surgery (as defined by the investigator) within 28 days prior to first dose of TAB004 or has not recovered to at least Grade 1 from adverse effects from such procedure, or anticipation of the need for major surgery during study treatment.
• 9. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to baseline or to NCI-CTCAE v5.0 Grade 0 or 1, or to levels dictated in the inclusion/exclusion criteria with the exception of neuropathies that are stable or improving and alopecia. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by TAB004 may be included (e.g., hearing loss) after consultation with the medical monitor.
• 10. Active or prior documented autoimmune disease, such as but not limited to systemic lupus erythematosus, multiple sclerosis, inflammatory bowel diseases, rheumatoid arthritis, autoimmune hepatitis, systemic sclerosis, autoimmune vasculitis, autoimmune neuropathies or type 1 insulin-dependent diabetes mellitus. Note: Subjects with the following are not excluded: vitiligo; alopecia; Grave's disease not requiring systemic treatment other than thyroid hormone replacement (within the past 2 years) psoriasis not requiring systemic treatment; controlled celiac disease; subjects with a history of autoimmune hypothyroidism requiring only thyroid hormone replacement therapy; And type 2 diabetes, provided that it is adequately controlled.
• 11. Clinically significant (intracranial, gastrointestinal) bleeding within 2 weeks prior to screening.
• 12. Known history of tuberculosis.
• 13. Subjects with history of or current drug-induced interstitial lung disease or pneumonitis ≥ Grade 2.
• 14. Subjects who have discontinued prior immune therapy due to immune mediated adverse reaction(s).
• 15. Subjects who are known to be human immunodeficiency virus positive.
• 16. Subjects with evidence of hepatitis B or C virus infection, unless their hepatitis is considered to have been cured. (Note that subjects with prior hepatitis B virus infection must have HBV viral load < 100 IU/mL before study enrollment, and must be treated according to local standards; hepatitis C virus infection must have, before study enrollment, no detectable viral load and must be treated according to local standards).
• 17. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis). Infection-related bowel inflammation, such as Clostridium difficile colitis, is not excluded provided that it has been fully resolved for ≥ 6 weeks.
• 18. History of anaphylaxis, or eczema that cannot be controlled with topical corticosteroids asthma.
• 19. Adult asthma that is moderate or severe, or asthma that has required: hospitalization in the last 2 years; invasive mechanical ventilation ever; systemic corticosteroids in the past year for exacerbations; or more than two short acting beta agonist (e.g., albuterol) administrations per month for breakthrough asthma symptoms. A history of childhood asthma or the presence of mild adult asthma that at baseline has symptoms that can be controlled well with inhaled corticosteroids or short acting beta agonists will not be excluded.
• 20. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure according to New York Heart Association Functional Classification ≥ 3, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring adverse events from TAB004, or compromise the ability of the subject to give written informed consent.
• 21. Untreated central nervous system and leptomeningeal metastases or requiring ongoing treatment for these metastases, including corticosteroids. Subjects with previously treated brain metastases may participate provided they are clinically stable for at least 28 days prior to study entry, have no evidence of new or enlarging metastases, and are off steroids.
• 22. Receipt of live attenuated vaccination within 28 days prior to study entry or within 30 days of receiving TAB004.
• 23. Any condition or treatment or diagnostic test that, in the opinion of the investigator or sponsor, would interfere with evaluation of TAB004 or interpretation of subject safety or study results.
• 24. Pregnancy or breast feeding women.
Drug: TAB004, Drug: Toripalimab
Lymphoma, Lung/Thoracic, Melanoma, skin, Hodgkins Lymphoma, Lymphoid Leukemia, Non-Hodgkins Lymphoma, Advanced Unresectable Solid Tumor, Metastatic Solid Tumor
immunotherapy, BTLA, HVEM, check point inhibitor, solid tumor, non-small cell lung cancer, NSCLC, melanoma, lymphoma, monoclonal antibody, phase 1 trial
UT Southwestern
A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations
Phase 1 will evaluate the safety and tolerability at different dose levels of repotrectinib in pediatric and young adult subjects with advanced or metastatic malignancies harboring anaplastic lymphoma kinase (ALK), receptor tyrosine kinase encoded by the gene ROS1 (ROS1), or neurotrophic receptor kinase genes encoding TRK kinase family (NTRK1-3) alterations to estimate the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) and select the Pediatric Recommended Phase 2 Dose (RP2D). Phase 2 will determine the anti-tumor activity of repotrectinib in pediatric subjects with advanced or metastatic malignancies harboring ALK, ROS1, or NTRK1-3 alterations.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tanya Watt
128737
All
0 Years to 25 Years old
Phase 1/Phase 2
NCT04094610
STU-2019-1268
Key
• Documented genetic ALK, ROS1, or NTRK1-3 alteration (point mutation, fusion, amplification) as identified by local testing in a Clinical Laboratory Improvement Amendments (CLIA) laboratory in the US or equivalently accredited diagnostic lab outside the United States (US) is required.
• Phase 1: Age <12 years; Phase 2: Age 12- 25 years
• Prior cytotoxic chemotherapy is allowed.
• Prior immunotherapy is allowed.
• Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
• All subjects must have measurable disease by RECIST v1.1 or Response Assessment in Neuro-Oncology Criteria (RANO) criteria at time of enrollment.
• Subjects with a primary CNS tumor or CNS metastases must be neurologically stable on a stable or decreasing dose of steroids for at least 14 days prior to enrollment.
• Subjects must have a Lansky (< 16 years) or Karnofsky (≥ 16 years) score of at least
• 9. Life expectancy greater than or equal to 12 weeks.
• Adequate hematologic, renal and hepatic function. Phase 2
• Cohort Specific
• Cohort 1: Subjects with NTRK fusion gene positive (NTRK+) advanced solid tumors (including primary CNS tumors), that are tropomyosin receptor kinase (TRK) TKI naïve;
• Cohort 2: subjects with NTRK+ advanced solid tumors (including primary CNS tumors), that are TRK TKI pre-treated;
• Cohort 3: subjects with tumors or ALCL characterized by other ALK/ROS1/NTRK alterations or NTRK fusions without centrally confirmed measurable disease or not otherwise eligible for Cohort 1 or 2.
• Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by BICR prior to enrollment. Key Exclusion Criteria (Phase 1 and Phase 2):
• Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only.
• Major surgery within 14 days (2 weeks) of start of repotrectinib treatment. Central venous access (Broviac, Mediport, etc.) placement does not meet criteria for major surgery.
• Known active infections (bacterial, fungal, viral including HIV positivity).
• Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTc) > 480 msec obtained from three ECGs, using the screening clinic ECG machine-derived QTc value
• Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval > 250 msec)
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval
• Peripheral neuropathy of CTCAE ≥grade 2.
• Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.
Inclusion Criteria:
• Documented genetic ALK, ROS1, or NTRK1-3 alteration (point mutation, fusion, amplification) as identified by local testing in a Clinical Laboratory Improvement Amendments (CLIA) laboratory in the US or equivalently accredited diagnostic lab outside the United States (US) is required.
• Phase 1: Age <12 years; Phase 2: Age 12- 25 years
• Prior cytotoxic chemotherapy is allowed.
• Prior immunotherapy is allowed.
• Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
• All subjects must have measurable disease by RECIST v1.1 or Response Assessment in Neuro-Oncology Criteria (RANO) criteria at time of enrollment.
• Subjects with a primary CNS tumor or CNS metastases must be neurologically stable on a stable or decreasing dose of steroids for at least 14 days prior to enrollment.
• Subjects must have a Lansky (< 16 years) or Karnofsky (≥ 16 years) score of at least
• 9. Life expectancy greater than or equal to 12 weeks.
• Adequate hematologic, renal and hepatic function. Phase 2
Inclusion Criteria:
• Cohort Specific
Inclusion Criteria:
• Cohort 1: Subjects with NTRK fusion gene positive (NTRK+) advanced solid tumors (including primary CNS tumors), that are tropomyosin receptor kinase (TRK) TKI naïve;
• Cohort 2: subjects with NTRK+ advanced solid tumors (including primary CNS tumors), that are TRK TKI pre-treated;
• Cohort 3: subjects with tumors or ALCL characterized by other ALK/ROS1/NTRK alterations or NTRK fusions without centrally confirmed measurable disease or not otherwise eligible for Cohort 1 or 2.
• Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by BICR prior to enrollment. Key Exclusion Criteria (Phase 1 and Phase 2):
• Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only.
• Major surgery within 14 days (2 weeks) of start of repotrectinib treatment. Central venous access (Broviac, Mediport, etc.) placement does not meet criteria for major surgery.
• Known active infections (bacterial, fungal, viral including HIV positivity).
• Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTc) > 480 msec obtained from three ECGs, using the screening clinic ECG machine-derived QTc value
• Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval > 250 msec)
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval
• Peripheral neuropathy of CTCAE ≥grade 2.
• Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.
Drug: Oral repotrectinib (TPX-0005)
Lymphoma, Locally Advanced Solid Tumors, Metastatic Solid Tumors, Primary CNS Tumors, Breast - Female, Breast - Male, Colon, Kidney, Lung/Thoracic, Rectum, Thyroid, Urinary Bladder, Soft Tissue
ALK, ROS1, NTRK1-3, Primary CNS tumor, anaplastic large cell lymphoma, metastatic solid tumor, advanced solid tumor, sarcoma, infantile fibrosarcoma, glioblastoma, soft tissue schwannoma, solitary fibrous tumor, glioma, inflammatory myofibroblastic tumor, pediatric
Children’s Health
Mobile Health and Social Media Physical Activity Intervention Among Adolescent and Young Adult Childhood Cancer Survivors, the StepByStep Study
This phase III trial compares a multi-component mobile health and social media physical activity intervention versus wearing a physical activity tracker alone among adolescent and young adult childhood cancer survivors. Regular physical activity helps maintain healthy weight, energy levels, and health. Adolescents and young adults who complete treatment for cancer are often less active. They may gain weight and have more health problems compared to people the same age who have not had treatment for cancer. Comparing the 2 programs will help researchers learn how to increase physical activity levels over time and also how changes in physical activity levels affect health and quality of life over time.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Ksenya Shliakhtsitsava
181933
All
15 Years to 20 Years old
Phase 3
NCT04089358
STU-2020-1255
Inclusion Criteria:
• First diagnosis of malignant neoplasm (International Classification of Diseases for Oncology [ICD-O] behavior code of "3") in first and continuous remission at the time of enrollment
• Curative cancer treatment must have included chemotherapy (including cellular therapy) and/or radiation (including radioactive iodine)
• Note: Childrens Oncology Group (COG) therapeutic trial participation is not required
• All cancer treatment must have been completed within 3-36 calendar months prior to enrollment
• Patients must have a life expectancy of > 1 year
• Self-report of < 420 minutes of moderate-to-vigorous physical activity per week as assessed via the study-specific Physical Activity Worksheet
• Note: See COG Study Web Page for the Godin-Shephard Leisure Time Physical Activity Questionnaire or link to online calculator
• Ambulatory and no known medical contraindications to increasing physical activity
• Note: Patients with amputation, rotationplasty, or other prothesis are not automatically excluded as long as they are ambulatory and have no known medical contraindications to increasing physical activity and all other eligibility criteria are satisfied
• No known significant physical or cognitive impairment that would prevent use of the electronic devices used for the protocol intervention (e.g. Fitbit, smartphone, tablet, or computer)
• Able to read and write English
• Note: For patients < 18 years, consenting parent/legal guardian does not have to be able to read and write English
• All patients and/or their parents or legal guardians must sign a written informed consent
• Note: Informed consent may be obtained electronically/online if allowed by local site policy and Institutional Review Board (IRB)/Research Ethics Board (REB) of record
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
• Post-menarchal female patients who are pregnant or planning to become pregnant in the next year are excluded
• Note: Pregnancy status can be established by clinical history with patient. Post-menarchal female patients are eligible as long as they agree to use an effective contraceptive method (including abstinence) during study participation
• Patients with previous hematopoietic stem cell transplant (HSCT) are excluded
• Note: Patients with previous autologous HSCT, chimeric antigen receptor T-cell (CAR T-cell) therapy, and other cellular cancer therapies can participate as long as all other eligibility criteria are satisfied
Other: Educational Intervention, Device: FitBit, Other: Goal Setting, Other: Health Promotion and Education, Other: Media Intervention, Behavioral: Telephone-Based Intervention
Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm
Children’s Health
Circulating Tumor DNA Testing in Predicting Treatment for Patients With Stage IIA Colon Cancer After Surgery
This phase II/III trial studies how well circulating tumor deoxyribonucleic acid (ctDNA) testing in the blood works in predicting treatment for patients with stage IIA colon cancer after surgery. ctDNA are circulating tumor cells that are shed by tumors into the blood. Finding ctDNA in the blood means that there is very likely some small amounts of cancer that remain after surgery. However, this cancer, if detected, cannot be found on other tests usually used to find cancer, as it is too small. Testing for ctDNA levels may help identify patients with colon cancer after surgery who do benefit, and those who do not benefit, from receiving chemotherapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Syed Kazmi
177531
All
18 Years and over
Phase 2/Phase 3
NCT04068103
STU-2020-0434
Inclusion Criteria:
• The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histologically/pathologically confirmed stage IIA adenocarcinoma of the colon (T3, N0, M0) with at least 12 lymph nodes examined at the time of surgical resection.
• Appropriate for active surveillance (i.e., no adjuvant chemotherapy) at the discretion of and as documented by the evaluating oncologist based on current practice patterns.
• The distal extent of the tumor must be >= 12 cm from the anal verge on pre-surgical endoscopy (i.e., excluding rectal adenocarcinomas warranting treatment with chemoradiation). If the patient did not undergo a pre-surgical endoscopy, then the distal extent of the tumor must be >= 12 cm from the anal verge as determined by surgical examination or pre-operative imaging.
• The patient must have had an en bloc complete gross resection of tumor (curative resection) as definitive surgical cancer treatment within 14 to 60 days of study randomization. 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.
• Availability and provision of adequate surgical tumor tissue for molecular diagnostics and confirmatory profiling.
• Absolute neutrophil count (ANC) must be >= 1200/mm^3 (within 28 days before randomization).
• Platelet count must be >= 100,000/mm^3 (within 28 days before randomization); and
• Hemoglobin must be >= 9 g/dL (within 28 days before randomization).
• Total bilirubin must be =< ULN (upper limit of normal) for the lab (within 28 days before randomization) unless the patient has a chronic grade 1 bilirubin elevation due to Gilbert?s disease or similar syndrome involving slow conjugation of bilirubin; and
• Alkaline phosphatase must be < 2.5 x ULN for the lab (within 28 days before randomization); and
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be < 1.5 x ULN for the lab (within 28 days before randomization).
• Serum creatinine =< 1.5 x ULN for the lab or measured or calculated creatinine clearance >= 50 mL/min using the Cockcroft-Gault formula for patients with creatinine levels > 1.5 x ULN for the lab (within 28 days before randomization).
• Pregnancy test (urine or serum according to institutional standard) done within 14 days before randomization must be negative (for women of childbearing potential only).
• Patients receiving a coumarin-derivative anticoagulant must agree to weekly monitoring of international normalized ratio (INR) if they are randomized to Arm 2 and receive capecitabine.
Exclusion Criteria:
• Colon cancer histology other than adenocarcinoma (i.e., neuroendocrine carcinoma, sarcoma, lymphoma, squamous cell carcinoma, etc.).
• Pathologic, clinical, or radiologic evidence of overt metastatic disease. This includes isolated, distant, or non-contiguous intra-abdominal metastases, even if resected (including the presence of satellite nodules constituting N1c disease in the absence of lymph node involvement).
• Tumor-related bowel perforation.
• History of prior invasive colon malignancy, regardless of disease-free interval.
• History of organ transplantation.
• Any prior systemic chemotherapy, targeted therapy, or immunotherapy; or radiation therapy administered as treatment for colorectal cancer (e.g., primary rectal adenocarcinomas for which treatment with neoadjuvant chemoradiation is warranted are not permitted).
• Other invasive malignancy within 5 years before randomization. Exceptions are colonic polyps, non-melanoma skin cancer or carcinoma-in-situ including those of the cervix and breast (DCIS).
• Synchronous primary rectal and/or colon cancers.
• Antineoplastic therapy (e.g., chemotherapy, targeted therapy, or immunotherapy) within 5 years before randomization. (For the purposes of this study, hormonal therapy is not considered chemotherapy.).
• Uncontrolled cardiac disease, in the opinion of the treating medical oncologist, that would preclude the use of any of the drugs included in the GI005 treatment regimen. This includes but is not limited to:
• Clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling temporary pacemaker.
• Ventricular tachycardia or supraventricular tachycardia that requires treatment with class Ia antiarrhythmic drugs (e.g., quinidine, procainamide, disopyramide) or class III antiarrhythmic drug (e.g., sotalol, amiodarone, dofetilide). Use of other antiarrhythmic drugs is permitted.
• Second- or third-degree atrioventricular (AV) block unless treated with a permanent pacemaker.
• Complete left bundle branch block (LBBB) unless treated with a permanent pacemaker.
• Sensory or motor neuropathy >= grade 2, according to Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.
• Active seizure disorder uncontrolled by medication.
• Active or chronic infection requiring systemic therapy.
• Known homozygous DPD (dihydropyrimidine dehydrogenase) deficiency.
• Pregnancy or lactation at the time of randomization.
• Co-morbid illnesses or other concurrent disease that, in the judgement of the clinician obtaining informed consent, 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).
• Prior testing with any available ctDNA test as part of the management of colon cancer, is not permitted.
Drug: Capecitabine, Drug: Fluorouracil, Drug: Leucovorin, Drug: Leucovorin Calcium, Drug: Oxaliplatin, Other: Patient Observation
Colon Adenocarcinoma, Colon, Rectum, Stage IIA Colon Cancer AJCC v8
UT Southwestern
Testing the Addition of a New Anti-cancer Drug, Radium-223 Dichloride, to the Usual Treatment (Cabozantinib) for Advanced Renal Cell Cancer That Has Spread to the Bone, the RadiCaL Study
This phase II trial studies whether adding radium-223 dichloride to the usual treatment, cabozantinib, improves outcomes in patients with renal cell cancer that has spread to the bone. Radioactive drugs such as radium-223 dichloride may directly target radiation to cancer cells and minimize harm to normal cells. Cabozantinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving radium-223 dichloride and cabozantinib may help lessen the pain and symptoms from renal cell cancer that has spread to the bone, compared to cabozantinib alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Suzanne Cole
42296
All
18 Years and over
Phase 2
NCT04071223
STU-2020-0639
Inclusion Criteria:
• Documented histologic or cytologic diagnosis of renal cell cancer (RCC). All subtypes of RCC are eligible including but not limited to clear cell, papillary, chromophobe, translocation, collecting duct carcinoma, medullary carcinoma, and unclassified categories. Enrollment of non-clear cell patients will be limited to 20% of the total sample size (~ 42 patients). Once this goal is met, accrual of non-clear cell patients will be discontinued (a notice will be sent out 2 weeks in advance). Sarcomatoid and rhabdoid differentiation are allowed
• Presence of at least 1 metastatic bone lesion not treated with prior radiation is required.
• The presence of bone metastases can be detected by computed tomography (CT), magnetic resonance imaging (MRI), Tc-99m bone scan or positron emission tomography (PET) (fludeoxyglucose F-18 [FDG] or sodium fluoride [NaF]) imaging. Patients with non-measurable bone-only disease are allowed. Patients may have received prior radiation therapy for bone metastases or other external radiation >= 7 days prior to registration, as long as they still have at least 1 metastatic bone lesion not treated with radiation. Patients with visceral metastases are allowed, as long as they have at least one untreated bone metastases
• No prior treatment with cabozantinib
• No treatment with any type of small molecular kinase inhibitor (including investigational kinase inhibitors) within 2 weeks or 5 half-lives (whichever is shorter) of registration or receipt of any anti-cancer therapy (including investigational therapy, monoclonal antibodies, cytokine therapy) within 3 weeks of registration
• No prior hemibody external radiotherapy
• No prior therapy with radium-223 dichloride or systemic radiotherapy (such as samarium, strontium)
• No major surgery within 6 weeks of randomization. Procedures such as thoracentesis, paracentesis, percutaneous biopsy, Moh's or other topical skin surgery, Lasik eye surgery are not considered major surgery. Patients who have had a nephrectomy may be registered >= 3 weeks after surgery, providing there are no wound-healing complications. Subjects with clinically relevant ongoing complications from prior surgery are not eligible
• Recovery to baseline or =< grade 1 CTCAE version 5.0 from toxicity related to any prior treatment, unless adverse events are clinically nonsignificant and/or stable on supportive therapy
• The use of osteoclast targeted therapy including either bisphosphonates or denosumab is mandated on this study except in patients with contraindications as determined by the treating investigator, including:
• Hypocalcemia
• Hypophosphatemia
• Renal impairment including those with a glomerular filtration rate (GFR) < 35 mL/min using the Cockcroft-Gault equation or acute renal impairment
• Hypersensitivity to drug formulation
• Dental condition or need for dental intervention that per the investigator would increase the risk of osteonecrosis of jaw (ONJ).
• Use of osteoclast targeted therapy or reason against use needs to be recorded in the electronic case report form (eCRF). Additionally, reason for discontinuation of osteoclast targeted therapy need to be appropriately documented in the eCRF
• Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown.
• Therefore, for women of childbearing potential only, a negative urine pregnancy test done =< 28 days prior to registration is required. A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
• Karnofsky performance status >= 60%
• No brain metastases or cranial epidural disease unless 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. 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
• No imminent or established spinal cord compression based on clinical symptoms and/or imaging. In patients with untreated imminent or established spinal cord compression, treatment with standard of care as clinically indicated should be completed at least 2 weeks before registration
• No imminent or impending pathologic fracture based on clinical symptoms and/or imaging. In patients with untreated imminent or impending pathologic fracture, treatment with standard of care as clinically indicated should be completed at least 2 weeks before registration
• No significant, uncontrolled intercurrent or recent illness, including but not limited to the following conditions:
• Cardiovascular disorders: Symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia; uncontrolled hypertension defined as sustained blood pressure > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment; stroke (including transient ischemic attack), myocardial infarction, or other ischemic event, within 6 months before randomization; thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 1 month before randomization
• Gastrointestinal disorders: Disorders associated with a high risk of perforation or fistula formation: active inflammatory bowel disease, active diverticulitis, active cholecystitis, active symptomatic cholangitis or active appendicitis, active acute pancreatitis or active acute obstruction of the pancreatic or biliary duct, or active gastric outlet obstruction; abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 3 months before randomization. Note: Complete healing of an intra-abdominal abscess must be confirmed before randomization
• No clinically significant hematuria, hematemesis, or hemoptysis, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 3 months before randomization
• No lesions invading major pulmonary blood vessels
• No other clinically significant disorders:
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy (with no medications prohibited by this protocol [e.g. drug-drug interactions]) with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy (with no medications prohibited by this protocol [e.g. drug-drug interactions]), 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 (with no medications prohibited by this protocol [e.g. drug-drug interactions])
• No serious non-healing wound or ulcer
• No malabsorption syndrome
• No uncompensated/symptomatic hypothyroidism
• No moderate to severe hepatic impairment (Child-Pugh B or C)
• No requirements for hemodialysis or peritoneal dialysis
• No history of solid organ transplantation
• No chronic concomitant treatment with strong CYP3A4 inducers or inhibitors. Because the list of these agents is constantly changing, it is important to regularly consult a frequently updated medical reference. Patients may not have received a strong CYP3A4 inducer within 12 days prior to registration nor a strong CYP3A4 inhibitor within 7 days prior to registration
• No concomitant anticoagulation 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 include:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low 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.
• Absolute neutrophil count (ANC) >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• Hemoglobin >= 9 g/dl (transfusions allowed)
• Calculated (calc.) creatinine clearance >= 30 mL/min using the Cockcroft-Gault equation
• Total bilirubin =< 1.5 x upper limit of normal (ULN), for patients with Gilberts disease =< 3.0 x ULN
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 x ULN
• Urine protein to creatinine (UPC) ratio =< 2 mg/mg OR 24-hr urine protein < 2 g
Drug: Cabozantinib S-malate, Other: Quality-of-Life Assessment, Other: Questionnaire Administration, Radiation: Radium Ra 223 Dichloride
Advanced Renal Cell Carcinoma, Clear Cell Renal Cell Carcinoma, Papillary Renal Cell Carcinoma, Metastatic Malignant Neoplasm in the Bone, Unclassified Renal Cell Carcinoma, Chromophobe Renal Cell Carcinoma, Kidney Medullary Carcinoma, Stage IV Renal Cell Cancer AJCC v8, Collecting Duct Carcinoma
UT Southwestern
Radiation Medication (Radium-223 Dichloride) Versus Radium-223 Dichloride Plus Radiation Enhancing Medication (M3814) Versus Radium-223 Dichloride Plus M3814 Plus Avelumab (a Type of Immunotherapy) for Advanced Prostate Cancer Not Responsive to Hormonal Therapy
This phase I/II trial studies the best dose of M3814 when given together with radium-223 dichloride or with radium-223 dichloride and avelumab and to see how well they work in treating patients with castrate-resistant prostate cancer that had spread to other places in the body (metastatic). M3814 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radioactive drugs, such as radium-223 dichloride, may carry radiation directly to tumor cells and not harm normal cells. Immunotherapy with monoclonal antibodies, such as avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This study is being done to find out the better treatment between radium-223 dichloride alone, radium-223 dichloride in combination with M3814, or radium-223 dichloride in combination with both M3814 and avelumab, to lower the chance of prostate cancer growing or spreading in the bone, and if this approach is better or worse than the usual approach for advanced prostate cancer not responsive to hormonal therapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kevin Courtney
131906
Male
18 Years and over
Phase 1/Phase 2
NCT04071236
STU-2021-1040
Inclusion Criteria:
• PHASE 1: Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
• PHASE 2: ECOG performance status =< 2 (Karnofsky >= 60%)
• Unless a patient has had orchiectomy by surgery, the patient is expected to be on antiandrogen therapy (ADT) for "medical castration". ADT needs to be maintained throughout the study. Testosterone level should be checked, and kept consistently lower than 50 ng/dL, similar to that obtained with bilateral orchiectomy
• Progressive castration-resistant prostate cancer with two or more skeletal metastases identified by 99mTC bone scintigraphy. One or more lymph node metastases allowed, but not mandatory. Lymph node metastases in each individually must measure less than 3 cm in the longest dimension. Visible visceral organ metastases are not allowed. A diagnosis of prostate cancer must have been histologically confirmed at any time point
• Baseline prostatic specific antigen (PSA) level of 1 ng/mL or higher with evidence of progressively increasing PSA values (two consecutive increases over the previous reference value)
• Progression after at least one of the following: abiraterone, enzalutamide, apalutamide, darolutamide, or taxane chemotherapy (docetaxel, cabazitaxel). There is no maximum number of prior therapies. Prior immunotherapies (for example, Sipuleucel-T or pembrolizumab) do not exclude the patient from participation
• Age >= 18 years. Castrate-resistant prostate cancer (CRPC) affects older adults and is rarely encountered in children and adolescents
• Life expectancy >= 6 months
• Albumin > 2.5 mg/dL
• Hemoglobin > 9 mg/dL
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (with the exception of < 3 mg/dL for patients with Gilbert's disease)
• Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN
• Creatinine =< 1.5 x institutional ULN OR
• Glomerular filtration rate (GFR) >= 40 mL/min/1.73 m^2
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy (with no medications prohibited by this protocol [e.g. drug-drug interactions]) with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy (with no medications prohibited by this protocol [e.g. drug-drug interactions]), 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 (with no medications prohibited by this protocol [e.g. drug-drug interactions])
• 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 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
• Concomitant use of physiologic corticosteroids is allowed
• Concomitant use of bisphosphonates is allowed (use of bone health agents is mandatory
• either denosumab [preferred] or bisphosphonates)
• The effects of radium-223 dichloride, M3814, and avelumab on the developing human fetus are unknown. 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 6 months after completion of Radium-223 dichloride, M3814, and avelumab administration
• Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible
• Patients must be able to swallow orally administered medication
• Patients with asymptomatic, treated brain metastases are permitted if there is no evidence of progression for at least 4 weeks after central nervous system (CNS)-directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT] scan) during the screening period
Exclusion Criteria:
• Active autoimmune conditions or patients on chronic immunosuppression due to underlying autoimmune condition
• Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia
• Prior therapy with radionuclides (e.g., strontium, samarium, rhenium, radium)
• Patients who are receiving any other investigational agents
• Patients who have had previous hemibody external radiation
• Patients who have had systemic radiotherapy with radioisotopes
• Patients who have imminent/established spinal cord compression, pathological fracture in weight bearing bones or bone lesion with soft tissue component unless treated as appropriate with radiation and/or surgery before starting on trial
• Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to radium-223 dichloride, M3814, or avelumab
• Patients unable to discontinue medications or substances that are potent inhibitors, inducers or sensitive substrates of CYP3A4/5 or CYP2C19 prior to study treatment are ineligible.
• Medications or substances that are strong inhibitors of CYP3A4/5 or CYP2C19 must be discontinued at least 1 week prior to first M3814 dose.
• Medications or substances that are strong inducers of CYP3A4/5 or CYP2C19 must be stopped at least 3 weeks prior to the first M3814 dose.
• Drugs mainly metabolized by CYP3A with a narrow therapeutic index (as judged by the Investigator or authorized designee) must be discontinued at least 1 day prior to first M3814 dose.
• Note: Because the lists of these agents are constantly changing, it is important to regularly consult a frequently- updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the- counter medicine or herbal product.
• Patients with uncontrolled intercurrent illness
• Patients with psychiatric illness/social situations that would limit compliance with study requirements
• Patients must not have an active infection requiring systemic treatment
• Patients must not use immunosuppressive medication =< 7 days of registration, EXCEPT for the following:
• Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)
• Systemic corticosteroids at physiologic doses =< 10 mg/day of prednisone or equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
• Patients who cannot discontinue concomitant H2 blockers or proton-pump inhibitors (PPIs). Patients may confer with the study doctor to determine if such medications can be discontinued. These must be discontinued >= 5 days prior to study treatment. Patients do not need to discontinue calcium carbonate
• Patients receiving sorivudine or any chemically related analogues (such as brivudine) are excluded
• Patients with a known history or present osteonecrosis of the jaw
Drug: Avelumab, Drug: Peposertib, Other: Quality-of-Life Assessment, Other: Questionnaire Administration, Radiation: Radium Ra 223 Dichloride
Metastatic Prostate Carcinoma, Stage IV Prostate Cancer AJCC v8, Prostate, Metastatic Malignant Neoplasm in the Lymph Nodes, Castration-Resistant Prostate Carcinoma
UT Southwestern
A Study of FF-10850 Topotecan Liposome Injection in Advanced Solid Tumors
To determine the safety profile, maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and recommended Phase 2 dose (RP2D) of FF-10850 (topotecan liposome injection) in patients with advanced solid tumors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Sanjay Chandrasekaran
202923
All
18 Years and over
Phase 1
NCT04047251
STU-2022-0554
Inclusion Criteria:
Patients must meet all the following criteria to participate in the study:
• Males and females ≥ 18 years of age
• Dose-escalation phase: Histologically or cytologically confirmed metastatic and/or unresectable solid tumor, relapsed or refractory to standard therapy, or for which no standard therapy is available that is expected to improve survival by at least 3 months
• At least 3 weeks beyond the last chemotherapy (or 3 half-lives, whichever is shorter), radiotherapy, major surgery, or experimental treatment, and recovered from all acute toxicities (≤ Grade 1), prior to the first dose of FF-10850
• Adequate performance status: Eastern Cooperative Oncology Group (ECOG) ≤ 1
• Life expectancy of ≥ 3 months
• Adequate hematologic parameters without ongoing transfusion support:
• Hemoglobin (Hb) ≥ 9 g/dL
• Absolute neutrophil count (ANC) ≥ 1.0 × 109 cells/L
• Platelets ≥ 100 × 109 cells/L
• Creatinine ≤ 1.5 × ULN, or calculated creatinine clearance ≥ 50 mL/minute by either the Cockcroft-Gault formula or as measured by a 24-hour urine collection
• Total bilirubin ≤ 2 × ULN unless due to Gilbert's disease; patients with Gilbert's disease who have a total bilirubin > 6 mg/dL are to be excluded
• ALT and AST ≤ 2.5 times ULN, or < 5 × ULN for patients with liver metastases
• QT interval corrected for rate (QT interval corrected for rate using Fridericia's Correction Formula, QTcF) ≤ 470 msec for women and ≤ 450 msec for men on the ECG obtained at Screening and confirmed pre-treatment on Cycle 1 Day 1.
• Patient must be willing to undergo a tumor biopsy, if the patient has a biopsy-accessible tumor
Exclusion Criteria:
• Patients who have not received standard/approved therapies expected to improve survival by at least 3 months
• History of severe hypersensitivity reactions to topotecan
• Serious cardiac condition within the last 6 months, such as uncontrolled arrhythmia, myocardial infarction, unstable angina or heart disease defined by the New York Heart Association (NYHA) Class III or Class IV or hereditary long QT syndrome
• Concomitant medication(s) that may cause QTc prolongation or induce Torsades de Pointes, except for antimicrobials that are used as standard of care to prevent or treat infections and other such drugs that are considered by the Investigator to be essential for patient care
• Active central nervous system (CNS) malignant disease in patients with a history of CNS malignancy. Patients with previously treated stable brain metastases are allowed if they have been stable off steroid therapy for at least 4 weeks.
• Known positive for human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HBsAg) or hepatitis C virus (HCV)
• Active infection requiring intravenous (IV) antibiotic usage within the last week prior to study treatment
• 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
• Pregnant or breast-feeding
Drug: FF-10850 Topotecan Liposome Injection
Advanced Solid Tumors, Other Skin
UT Southwestern
A Study of CC-99712, a BCMA Antibody-Drug Conjugate, in Participants With Relapsed and Refractory Multiple Myeloma
Study CC-99712-MM-001 is an open-label, Phase 1, dose escalation (Part A) and expansion (Part B), First-in-Human (FIH) clinical study of CC-99712 in monotherapy or combination with BMS-986405 in participants with relapsed and refractory multiple myeloma (MM). The dose escalation part (Part A) of the study will evaluate the safety and tolerability of escalating doses of CC-99712, administered intravenously (IV) in monotherapy (Arm 1) or combination with BMS-986405 (Arm 2), to determine the maximum tolerated dose (MTD) of CC-99712 guided by a Bayesian logistic regression model (BLRM). A modified accelerated titration design will also be used for Arm 1 and Arm 2. The MTD may be established separately for CC-99712 administered at Q3W and/ or Q4W schedules. The expansion part (Part B) will further evaluate the safety and efficacy of CC-99712 in monotherapy (Arm 1) or combination (Arm 2) administered at or below the MTD in selected expansion cohorts in order to determine the RP2D. One or more doses or dosing regimens may be selected for cohort expansion. All participants will be treated until confirmed disease progression per IMWG criteria, unacceptable toxicity, or participants//Investigator decision to withdraw.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Larry Anderson
102991
All
18 Years and over
Phase 1
NCT04036461
STU-2019-1325
Participants must satisfy the following criteria to be enrolled in the study:
Inclusion
• Participant is ≥ 18 years of age at the time of signing the ICF.
• Participant has a history of multiple myeloma (MM) with relapsed and/or refractory disease
• Participant must have measurable disease.
• Participant has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1. Exclusion Criteria
• Participant has symptomatic central nervous system involvement of MM.
• Participant had a prior autologous stem cell transplant ≤ 3 months prior to starting CC-99712.
• Participant had a prior allogeneic stem cell transplant with either standard or reduced intensity conditioning ≤ 6 months prior to starting CC-99712 or is on systemic immunosuppression for graft-versus host disease.
• Subject is a pregnant or lactating female.
• Subject has known human immunodeficiency virus (HIV) infection.
• Subject has active hepatitis B or C (HBV/HCV) infection. Other protocol-defined inclusion/exclusion criteria apply
• Participant is ≥ 18 years of age at the time of signing the ICF.
• Participant has a history of multiple myeloma (MM) with relapsed and/or refractory disease
• Participant must have measurable disease.
• Participant has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1. Exclusion Criteria
• Participant has symptomatic central nervous system involvement of MM.
• Participant had a prior autologous stem cell transplant ≤ 3 months prior to starting CC-99712.
• Participant had a prior allogeneic stem cell transplant with either standard or reduced intensity conditioning ≤ 6 months prior to starting CC-99712 or is on systemic immunosuppression for graft-versus host disease.
• Subject is a pregnant or lactating female.
• Subject has known human immunodeficiency virus (HIV) infection.
• Subject has active hepatitis B or C (HBV/HCV) infection. Other protocol-defined inclusion/exclusion criteria apply
Drug: CC-99712, Drug: BMS-986405
Multiple Myeloma
Multiple Myeloma, Relapsed and refractory, CC-99712, BCMA, Antibody drug conjugate, BMS-986405
UT Southwestern
67Cu-SARTATE™ Peptide Receptor Radionuclide Therapy Administered to Pediatric Patients With High-Risk, Relapsed, Refractory Neuroblastoma
The aim of this study is to evaluate the safety and efficacy of 67Cu-SARTATE in pediatric patients with high-risk neuroblastoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tanya Watt
128737
All
Not specified
Phase 1/Phase 2
NCT04023331
STU-2020-1005
Inclusion Criteria:
• Participant is able and willing to provide informed consent (≥18 years), or informed consent is obtained by the parent or legal guardian for minor participants, with the minor providing age appropriate assent, according to local law and regulations;
• Life expectancy ≥ 12 weeks;
• Known high-risk neuroblastoma OR previously intermediate-risk neuroblastoma that has relapsed or progressed to high-risk, with failure to achieve complete response with standard therapy (defined as at least 4 cycles of aggressive multi-drug induction chemotherapy with or without radiation and surgery, or according to a standard high-risk treatment/neuroblastoma protocol), OR who are medically ineligible to receive standard treatment OR who are intolerant to standard treatment;
• Adequate recovery from acute toxic effects of any prior therapy, as deemed by the Investigator or treating Sub-Investigator;
• Adequate liver function as defined by the following laboratory values obtained within 28 days prior to administration of 64Cu-SARTATE: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3.0 x upper limit of normal (ULN);
• Adequate renal function;
• Adequate laboratory parameters: Absolute neutrophil count > 1.0 x 10 9/L; Platelet count > 50 x 10 9/L; Total bilirubin <1.5 x ULN;
• Karnofsky or Lansky performance status ≥50;
• All participants must have a hematopoietic stem cell product available (minimum CD34+ cell dose is ≥2 x 10 6 cells/kg);
• Sexually active participants of reproductive potential must practice an effective method of birth control while participating on this study, to avoid possible damage to the fetus. Abstinence is considered acceptable;
• 64Cu-SARTATE uptake on the 4 hour scan (SUVmax) of any lesion equal to or higher than that of the liver in order to move on to the therapy phase of the study.
Exclusion Criteria:
• Participants with disease of any major organ system that would compromise their ability to tolerate therapy, as deemed by the Investigator or treating Sub-Investigator;
• Any other active malignancy, or a history of prior malignancy within the past 3 years;
• History of cardiac failure as evidenced by: dyspnea at rest, exercise intolerance, oxygen requirement, clinically significant cardiac dysfunction;
• Planned administration of chemotherapy, anti-cancer cytokine therapy, immunotherapy or radiotherapy within 2 weeks prior to the administration of 64Cu-SARTATE;
• Administration of therapeutic dose of 131I-MIBG within 8 weeks prior to the administration of 64Cu-SARTATE;
• External beam radiation therapy (EBRT) to both kidneys or a single functioning kidney within 12 months prior to the administration of 64Cu-SARTATE;
• Administration of any investigational agents within 21 days prior to administration of 64Cu-SARTATE;
• Treatment with long acting somatostatin analogues (administered within 28 days prior to the administration of 64Cu-SARTATE), or short acting somatostatin analogues (administered within 24 hours prior to the administration of 64Cu-SARTATE);
• Known sensitivity or allergy to somatostatin analogues;
• Previous peptide receptor radionuclide therapy (PRRT);
• Female participants who are pregnant or lactating;
• Participants who are on hemodialysis;
• QTc interval ≥ 0.45 seconds as measured by Screening ECG;
• Participants with uncontrolled infection(s);
• Any medical condition which the Investigator feels may interfere with the procedures or evaluations of the study;
• Participants 12 months and younger will be excluded from cohorts where the planned single or cumulative administered activity is modelled to deliver a radiation dose to the marrow that exceeds 2 Gy.
Drug: 67Cu-SARTATE, Drug: 64Cu-SARTATE
Neuroblastoma, Refractory Neuroblastoma, Relapsed Neuroblastoma
Children’s Health
Study to Compare the Efficacy and Safety of NT 201 (Botulinum Toxin) With Placebo for the Treatment of Lower Limb Spasticity Caused by Stroke or Traumatic Brain Injury (PATTERN)
The purpose of this study is to determine whether a single treatment with administration of 400 Units NT 201 (botulinum toxin) is superior to placebo (no medicine) for the treatment of lower limb spasticity caused by stroke or traumatic brain injury (Main Period). Participants will be assigned to the treatment groups by chance and neither the participants nor the research staff who interact with them will know the allocation. The following 4 to 5 treatment cycles will investigate the safety and tolerability of treatment with NT 201 (botulinum toxin) when administered in doses between 400 and 800 Units (Open Label Extension Period). All participants will receive the treatment and the dose will depend on whether only lower limb spasticity or combined upper and lower limb spasticity are treated.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Fatma Gul
12837
All
18 Years to 85 Years old
Phase 3
NCT03992404
STU-2019-0894
Inclusion Criteria:
• Female or male subject ≥ 18 years and ≤ 85 years at screening
• Diagnosis of lower limb spasticity with or without upper limb spasticity of the same body side caused by stroke or traumatic brain injury
• Disabling ankle flexor spasticity presenting as pes equinus or pes equinovarus
• Modified Ashworth Scale-Bohannon [MAS] score of 2 or 3 points in the ankle plantar flexor of the target lower limb (supine position, knee extended)
• Minimum passive range of motion in ankle of the target lower limb (supine position, knee extended): 10°dorsiflexion and 20°plantarflexion
• At least 4 months since last botulinum neurotoxin [BoNT] injection for treatment of spasticity or any other condition
• For subjects receiving anticoagulation therapy, the investigator confirms and documents that the subject has an:
• Activated partial thromboplastin time [aPTT] ≤ 80 seconds (subjects on dabigatran or other direct thrombin inhibitors) or
• International normalized ratio [INR] value of ≤ 2.5 (subjects on coumarins or other anticoagulants monitored by INR)
Exclusion Criteria:
• Generalized disorders of muscle activity (e.g. myasthenia gravis, Lambert Eaton syndrome, amyotrophic lateral sclerosis) or any other significant peripheral neuromuscular dysfunction which might interfere with the study
• Bilateral lower limb paresis/paralysis/spasticity or tetraparesis/paralysis/spasticity
• Body weight < 50 kg
• Severe atrophy of the target limb muscles
• Previous, ongoing or planned treatments of spasticity with intrathecal baclofen
• Previous, ongoing, or planned treatments of spasticity in the target lower limb with any of the following procedures: Surgical Intervention; Alcohol or phenol block; Muscle afferent block
• Physiotherapy or use of orthoses or splints at the target limb initiated less than 4 weeks before screening or expected to change during the double blind phase of the study
• Current or planned treatment with parenterally administered drugs that interfere with neuromuscular transmission (e.g. intrathecal baclofen, tubocurarine type muscle relaxants used in anesthesia), or local anesthetics in the treated region within 2 weeks prior to screening
• Infection or inflammation at the injection sites
• Subjects with presence or history of aspiration pneumonia, recurrent lower respiratory tract infections, or compromised respiratory function as per investigator's clinical judgment
• Pregnancy (as verified by a positive pregnancy test) or breast feeding
Drug: NT 201, Drug: Placebo
Brain and Nervous System, Other, Lower Limb or Combined Lower Limb and Upper Limb Spasticity Due to Stroke or Traumatic Brain Injury
UT Southwestern; Parkland Health & Hospital System
STRATA: Safe Testing of Risk for AsymptomaTic MicrohematuriA
To evaluate the clinical utility associated with the integration of Cxbladder into the evaluation of subjects presenting with hematuria for evaluation of urothelial carcinoma (UC) without compromising detection of UC.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yair Lotan
59883
All
18 Years and over
N/A
NCT03988309
STU-2019-1020
Inclusion Criteria:
• Patient is undergoing investigation of recent confirmed hematuria, as defined by the AUA/SUFU Guideline (Barocas DA, Boorjian SA, Alvarez RD et al. Microhematuria: AUA/SUFU guideline, J Urol 2020; 204:778) (by either flexible or rigid cystoscopy/TURBT), including hematuria subjects referred due to suspicious/positive imaging, in order to determine the presence of urothelial carcinoma.
• Able to provide a voided urine sample of the required minimum volume
• Able to give written consent
• Able and willing to comply with study requirements
• Aged 18 years or older Exclusion Criteria
• Prior history of bladder malignancy or pelvic radiotherapy. Prior history prostate or renal cell carcinoma within the last 5 years.
• Prior genitourinary manipulation (flexible or rigid cystoscopy / catheterisation, urethral dilation) in the 14 days before urine collection,
• Known current pregnancy
Diagnostic Test: Cxbladder
Urothelial Carcinoma, Hematuria, Urinary Bladder
UT Southwestern
Study of Adjuvant Cemiplimab Versus Placebo After Surgery and Radiation Therapy in Patients With High Risk Cutaneous Squamous Cell Carcinoma
The primary objective of the study is to compare disease-free survival (DFS) of patients with high-risk cutaneous squamous cell carcinoma (CSCC) treated with adjuvant cemiplimab, versus those treated with placebo, after surgery and radiation therapy (RT). The secondary objectives of the study are: - To compare the overall survival (OS) of high-risk CSCC patients treated with adjuvant cemiplimab, versus those treated with placebo, after surgery and RT - To compare the effect of adjuvant cemiplimab with that of placebo on patients' freedom from locoregional recurrence (FFLRR) after surgery and RT - To compare the effect of adjuvant cemiplimab with that of placebo on patients' freedom from distant recurrence (FFDR) after surgery and RT - To compare the effect of adjuvant cemiplimab with that of placebo on the cumulative incidence of second primary CSCC tumors (SPTs) after surgery and RT - To evaluate the safety of adjuvant cemiplimab and that of placebo in high-risk CSCC patients after surgery and RT - To assess cemiplimab pharmacokinetics and immunogenicity in human serum
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Jade Homsi
175558
All
18 Years and over
Phase 3
NCT03969004
STU-2019-1140
Key
• For Japan only, men and women ≥21 years old
• Patient with resection of pathologically confirmed CSCC (primary CSCC lesion only, or primary CSCC with nodal involvement, or CSCC nodal metastasis with known primary CSCC lesion previously treated within the draining lymph node echelon), with macroscopic gross resection of all disease
• High risk CSCC, as defined in the protocol
• Completion of curative intent post-operative radiation therapy (RT) within 2 to 10 weeks of randomization
• Eastern Cooperative Oncology Group performance status (ECOG PS) ≤1
• Adequate hepatic, renal, and bone marrow function as defined in the protocol Key
• Squamous cell carcinomas (SCCs) arising in non-cutaneous sites as defined in the protocol
• Concurrent malignancy other than localized CSCC and/or history of malignancy other than localized CSCC within 3 years of date of randomization as defined in the protocol
• Patients with hematologic malignancies (note: patients with chronic lymphocytic leukemia (CLL) are not excluded if they have not required systemic therapy for CLL within 6 months of enrollment)
• Patients with history of distantly metastatic CSCC (visceral or distant nodal), unless the disease-free interval is at least 3 years (regional nodal involvement of disease in draining lymph node basin that was resected and radiated prior to enrollment will not be exclusionary)
• Ongoing or recent (within 5 years of randomization date) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events (irAEs). The following are not exclusionary: vitiligo, childhood asthma that has resolved, type 1 diabetes, residual hypothyroidism that required only hormone replacement, or psoriasis that does not require systemic treatment.
• Has had prior systemic anti-cancer immunotherapy for CSCC Note: Other protocol defined Inclusion/Exclusion criteria apply
Inclusion Criteria:
• For Japan only, men and women ≥21 years old
• Patient with resection of pathologically confirmed CSCC (primary CSCC lesion only, or primary CSCC with nodal involvement, or CSCC nodal metastasis with known primary CSCC lesion previously treated within the draining lymph node echelon), with macroscopic gross resection of all disease
• High risk CSCC, as defined in the protocol
• Completion of curative intent post-operative radiation therapy (RT) within 2 to 10 weeks of randomization
• Eastern Cooperative Oncology Group performance status (ECOG PS) ≤1
• Adequate hepatic, renal, and bone marrow function as defined in the protocol Key
Exclusion Criteria:
• Squamous cell carcinomas (SCCs) arising in non-cutaneous sites as defined in the protocol
• Concurrent malignancy other than localized CSCC and/or history of malignancy other than localized CSCC within 3 years of date of randomization as defined in the protocol
• Patients with hematologic malignancies (note: patients with chronic lymphocytic leukemia (CLL) are not excluded if they have not required systemic therapy for CLL within 6 months of enrollment)
• Patients with history of distantly metastatic CSCC (visceral or distant nodal), unless the disease-free interval is at least 3 years (regional nodal involvement of disease in draining lymph node basin that was resected and radiated prior to enrollment will not be exclusionary)
• Ongoing or recent (within 5 years of randomization date) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events (irAEs). The following are not exclusionary: vitiligo, childhood asthma that has resolved, type 1 diabetes, residual hypothyroidism that required only hormone replacement, or psoriasis that does not require systemic treatment.
• Has had prior systemic anti-cancer immunotherapy for CSCC Note: Other protocol defined Inclusion/Exclusion criteria apply
Drug: Cemiplimab, Drug: Placebo
Cutaneous Squamous Cell Carcinoma, Other Skin
High risk
UT Southwestern
A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma (GBM AGILE)
Glioblastoma (GBM) adaptive, global, innovative learning environment (GBM AGILE) is an international, seamless Phase II/III response adaptive randomization platform trial designed to evaluate multiple therapies in newly diagnosed (ND) and recurrent GBM.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Michael Youssef
200728
All
18 Years and over
Phase 2/Phase 3
NCT03970447
STU-2019-1281
Newly Diagnosed
• Age ≥ 18 years.
• Histologically confirmed Grade IV GBM, inclusive of gliosarcoma (WHO criteria; IDH wild-type by immunohistochemistry [IHC] or sequencing for IDH) established following either a surgical resection or biopsy. An MRI scan with the required imaging sequences performed within 21 days prior to randomization preferably. The post-operative MRI scan performed within 96 hours of surgery or the MRI scan performed for radiation therapy planning may serve as the MRI scan performed during screening if all required imaging sequences were obtained.
• Karnofsky performance status ≥ 60% performed within a 14-day window prior to randomization.
• Availability of tumor tissue representative of GBM from definitive surgery or biopsy. Recurrent
• Age ≥ 18 years.
• Histologically confirmed Grade IV GBM, inclusive of gliosarcoma (WHO criteria; IDH wild-type by immunohistochemistry [IHC] or sequencing for IDH) at first or second recurrence after initial standard, control or experimental therapy that includes at a minimum radiation therapy (RT).
• Evidence of recurrent disease demonstrated by disease progression using slightly modified Response Assessment in Neuro-Oncology (RANO) criteria.
• Two scans to confirm progression are required: at least 1 scan at the time of progression and 1 scan prior to the time of progression.
• Karnofsky performance status ≥ 70% performed within a 14-day window prior to randomization.
• Availability of tumor tissue representative of GBM from initial definitive surgery and/or, recurrent surgery, if performed. Newly Diagnosed
• Received any prior treatment for glioma including: a. Prior prolifeprospan 20 with carmustine wafer. b. Prior intracerebral, intratumoral, or cerebral spinal fluid (CSF) agent. c. Prior radiation treatment for GBM or lower-grade glioma. d. Prior chemotherapy or immunotherapy for GBM or lower-grade glioma. Receiving additional, concurrent, active therapy for GBM outside of the trial.
• Extensive leptomeningeal disease.
• QTc > 450 msec if male and QTc > 470 msec if female.
• History of another malignancy in the previous 2 years, with a disease-free interval of < 2 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Recurrent
• Early disease progression prior to 3 months (12 weeks) from the completion of RT.
• More than 2 prior lines for chemotherapy administration. (NOTE: In the 1st line adjuvant setting, combination of temozolomide (TMZ) with an experimental agent, is considered one line of chemotherapy.)
• Received any prior treatment with lomustine, agents part of any of the experimental arms, and bevacizumab or other vascular endothelial growth factor (VEGF) or VEGF receptor-mediated targeted agent.
• Any prior treatment with prolifeprospan 20 with carmustine wafer.
• Any prior treatment with an intracerebral agent.
• Receiving additional, concurrent, active therapy for GBM outside of the trial
• Extensive leptomeningeal disease.
• QTc > 450 msec if male and QTc > 470 msec if female.
• History of another malignancy in the previous 2 years, with a disease-free interval of < 2 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible.
Inclusion Criteria:
• Age ≥ 18 years.
• Histologically confirmed Grade IV GBM, inclusive of gliosarcoma (WHO criteria; IDH wild-type by immunohistochemistry [IHC] or sequencing for IDH) established following either a surgical resection or biopsy. An MRI scan with the required imaging sequences performed within 21 days prior to randomization preferably. The post-operative MRI scan performed within 96 hours of surgery or the MRI scan performed for radiation therapy planning may serve as the MRI scan performed during screening if all required imaging sequences were obtained.
• Karnofsky performance status ≥ 60% performed within a 14-day window prior to randomization.
• Availability of tumor tissue representative of GBM from definitive surgery or biopsy. Recurrent
Inclusion Criteria:
• Age ≥ 18 years.
• Histologically confirmed Grade IV GBM, inclusive of gliosarcoma (WHO criteria; IDH wild-type by immunohistochemistry [IHC] or sequencing for IDH) at first or second recurrence after initial standard, control or experimental therapy that includes at a minimum radiation therapy (RT).
• Evidence of recurrent disease demonstrated by disease progression using slightly modified Response Assessment in Neuro-Oncology (RANO) criteria.
• Two scans to confirm progression are required: at least 1 scan at the time of progression and 1 scan prior to the time of progression.
• Karnofsky performance status ≥ 70% performed within a 14-day window prior to randomization.
• Availability of tumor tissue representative of GBM from initial definitive surgery and/or, recurrent surgery, if performed. Newly Diagnosed
Exclusion Criteria:
• Received any prior treatment for glioma including: a. Prior prolifeprospan 20 with carmustine wafer. b. Prior intracerebral, intratumoral, or cerebral spinal fluid (CSF) agent. c. Prior radiation treatment for GBM or lower-grade glioma. d. Prior chemotherapy or immunotherapy for GBM or lower-grade glioma. Receiving additional, concurrent, active therapy for GBM outside of the trial.
• Extensive leptomeningeal disease.
• QTc > 450 msec if male and QTc > 470 msec if female.
• History of another malignancy in the previous 2 years, with a disease-free interval of < 2 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Recurrent
Exclusion Criteria:
• Early disease progression prior to 3 months (12 weeks) from the completion of RT.
• More than 2 prior lines for chemotherapy administration. (NOTE: In the 1st line adjuvant setting, combination of temozolomide (TMZ) with an experimental agent, is considered one line of chemotherapy.)
• Received any prior treatment with lomustine, agents part of any of the experimental arms, and bevacizumab or other vascular endothelial growth factor (VEGF) or VEGF receptor-mediated targeted agent.
• Any prior treatment with prolifeprospan 20 with carmustine wafer.
• Any prior treatment with an intracerebral agent.
• Receiving additional, concurrent, active therapy for GBM outside of the trial
• Extensive leptomeningeal disease.
• QTc > 450 msec if male and QTc > 470 msec if female.
• History of another malignancy in the previous 2 years, with a disease-free interval of < 2 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible.
Drug: Temozolomide, Drug: Lomustine, Drug: Regorafenib, Radiation: Radiation, Drug: Paxalisib, Drug: VAL-083, Drug: VT1021, Drug: Troriluzole, Drug: VT1021
Glioblastoma
Glioblastoma, Newly diagnosed, recurrent, O6-methylguanine-DNA-methyltransferase (MGMT) methylated, MGMT unmethylated, isocitrate dehydrogenase (IDH) wild-type, Bayesian, adaptive randomization, Master Protocol, Platform Trial, Phase 2, Phase 3
UT Southwestern
Inotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and B-LLy
This phase III trial studies whether inotuzumab ozogamicin added to post-induction chemotherapy for patients with High-Risk B-cell Acute Lymphoblastic Leukemia (B-ALL) improves outcomes. This trial also studies the outcomes of patients with mixed phenotype acute leukemia (MPAL), and B-lymphoblastic lymphoma (B-LLy) when treated with ALL therapy without inotuzumab ozogamicin. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a type of chemotherapy called calicheamicin. Inotuzumab attaches to cancer cells in a targeted way and delivers calicheamicin to kill them. Other drugs used in the chemotherapy regimen, such as cyclophosphamide, cytarabine, dexamethasone, doxorubicin, daunorubicin, methotrexate, leucovorin, mercaptopurine, prednisone, thioguanine, vincristine, and pegaspargase or calaspargase pegol work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial will also study the outcomes of patients with mixed phenotype acute leukemia (MPAL) and disseminated B lymphoblastic lymphoma (B-LLy) when treated with high-risk ALL chemotherapy. The overall goal of this study is to understand if adding inotuzumab ozogamicin to standard of care chemotherapy maintains or improves outcomes in High Risk B-cell Acute Lymphoblastic Leukemia (HR B-ALL). The first part of the study includes the first two phases of therapy: Induction and Consolidation. This part will collect information on the leukemia, as well as the effects of the initial treatment, in order to classify patients into post-consolidation treatment groups. On the second part of this study, patients will receive the remainder of the chemotherapy cycles (interim maintenance I, delayed intensification, interim maintenance II, maintenance), with some patients randomized to receive inotuzumab. Other aims of this study include investigating whether treating both males and females with the same duration of chemotherapy maintains outcomes for males who have previously been treated for an additional year compared to girls, as well as to evaluate the best ways to help patients adhere to oral chemotherapy regimens. Finally, this study will be the first to track the outcomes of subjects with disseminated B-cell Lymphoblastic Leukemia (B-LLy) or Mixed Phenotype Acute Leukemia (MPAL) when treated with B-ALL chemotherapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
67555
All
1 Year to 25 Years old
Phase 3
NCT03959085
STU-2019-1574
Inclusion Criteria:
• B-ALL and MPAL patients must be enrolled on APEC14B1 and consented to eligibility studies (Part A) prior to treatment and enrollment on AALL1732. Note that central confirmation of MPAL diagnosis must occur within 22 business days after enrollment for MPAL patients. If not performed within this time frame, patients will be taken off protocol.
• APEC14B1 is not a requirement for B-LLy patients but for institutional compliance every patient should be offered participation in APEC14B1. B-LLy patients may directly enroll on AALL1732.
• Patients must be > 365 days and < 25 years of age
• White blood cell count (WBC) criteria for patients with B-ALL (within 7 days prior to the start of protocol-directed systemic therapy):
• Age 1-9.99 years: WBC >= 50,000/uL
• Age 10-24.99 years: Any WBC
• Age 1-9.99 years: WBC < 50,000/uL with:
• Testicular leukemia
• CNS leukemia (CNS3)
• Steroid pretreatment.
• White blood cell count (WBC) criteria for patients with MPAL (within 7 days prior to the start of protocol-directed systemic therapy):
• Age 1-24.99 years: any WBC.
• Patient has newly diagnosed B-ALL or MPAL (by World Health Organization [WHO] 2016 criteria) with >= 25% blasts on a bone marrow (BM) aspirate;
• OR If a BM aspirate is not obtained or is not diagnostic of acute leukemia, the diagnosis can be established by a pathologic diagnosis of acute leukemia on a BM biopsy;
• OR A complete blood count (CBC) documenting the presence of at least 1,000/uL circulating leukemic cells if a bone marrow aspirate or biopsy cannot be performed.
• Patient has newly diagnosed B-LLy Murphy stages III or IV.
• Patient has newly diagnosed B-LLy Murphy stages I or II with steroid pretreatment.
• Note: For B-LLy patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to B-ALL. For tissue processed by other means (i.e., paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of B-LLy defined by the submitting institution will be accepted.
• All patients and/or their parents or legal guardians must sign a written informed consent.
• All institutional, Food and Drug Administration (FDA), and NCI requirements for human studies must be met.
Exclusion Criteria:
• Patients with Down syndrome are not eligible (patients with Down syndrome and B-ALL are eligible for AALL1731, regardless of NCI risk group).
• With the exception of steroid pretreatment or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for the current diagnosis of B-ALL, MPAL, or B-LLy or for any cancer diagnosed prior to initiation of protocol therapy on AALL1732.
• Patients who have received > 72 hours of hydroxyurea within one week prior to start of systemic protocol therapy.
• Patients with B-ALL or MPAL who do not have sufficient diagnostic bone marrow submitted for APEC14B1 testing and who do not have a peripheral blood sample submitted containing > 1,000/uL circulating leukemia cells.
• Patients with acute undifferentiated leukemia (AUL) are not eligible.
• For Murphy stage III/IV B-LLy patients, or stage I/II patients with steroid pretreatment, the following additional exclusion criteria apply:
• T-lymphoblastic lymphoma.
• Morphologically unclassifiable lymphoma.
• Absence of both B-cell and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma.
• Patients with known Charcot-Marie-Tooth disease.
• Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL, regardless of blast immunophenotype.
• Patients requiring radiation at diagnosis.
• 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 women who plan to breastfeed their infants while on study and for 2 months after the last dose of inotuzumab ozogamicin.
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of study participation. For those patients randomized to inotuzumab ozogamicin, there is a minimum of 8 months after the last dose of inotuzumab ozogamicin for females and 5 months after the last dose of inotuzumab ozogamicin for males.
Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspiration, Procedure: Bone Marrow Biopsy, Procedure: Bone Scan, Drug: Calaspargase Pegol-mknl, Procedure: Computed Tomography, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin Hydrochloride, Drug: Dexamethasone, Drug: Doxorubicin Hydrochloride, Biological: Inotuzumab Ozogamicin, Drug: Leucovorin Calcium, Procedure: Magnetic Resonance Imaging, Drug: Mercaptopurine, Drug: Methotrexate, Drug: Pegaspargase, Procedure: Positron Emission Tomography, Drug: Prednisolone, Other: Questionnaire Administration, Radiation: Radiation Therapy, Radiation: Radiation Therapy, Drug: Thioguanine, Drug: Vincristine Sulfate
B Acute Lymphoblastic Leukemia, Central Nervous System Leukemia, Testicular Leukemia, Mixed Phenotype Acute Leukemia, B Lymphoblastic Lymphoma
Children’s Health
Markers of Osteoporosis in Cystic Fibrosis
Main Study Up to 100 subjects, both non-CF volunteers and Cystic Fibrosis (CF) patients, will participate in a single study visit that will include a DEXA scan, micro CT, and blood collection. Denosumab (Prolia) Sub study Approximately 10 adult subjects with CF who participated in the main study and have results indicating bone disease will receive treatment with Denosumab for up to 5 years. They will be asked to return annually for repeat DEXA scans, micro CT, and blood collection.
Call 214-648-5005
studyfinder@utsouthwestern.edu, YAMEI.CHENG@UTSouthwestern.edu
Raksha Jain
19733
All
18 Years to 64 Years old
Phase 4
NCT03921060
STU 052018-007
Cystic Fibrosis Main Study
• Must have CF diagnosis confirmed by sweat test or genotype analysis
• Subjects (and parents/legal guardians as applicable) must have the ability to read and write in English Sub-study
• No CF diagnosis
• Men or women without osteoporosis
• Less than 18 years of age
• Unwilling to return annually for study visits for up to 5 years
• Unwilling and/or medically unable to take denosumab
Inclusion Criteria:
• Must have CF diagnosis confirmed by sweat test or genotype analysis
• Subjects (and parents/legal guardians as applicable) must have the ability to read and write in English Sub-study
Exclusion Criteria:
• No CF diagnosis
• Men or women without osteoporosis
• Less than 18 years of age
• Unwilling to return annually for study visits for up to 5 years
• Unwilling and/or medically unable to take denosumab
Drug: Denosumab
Cystic Fibrosis, Bones and Joints, Lung/Thoracic
UT Southwestern; Children’s Health
Dabrafenib Combined With Trametinib After Radiation Therapy in Treating Patients With Newly-Diagnosed High-Grade Glioma
This phase II trial studies how well the combination of dabrafenib and trametinib works after radiation therapy in children and young adults with high grade glioma who have a genetic change called BRAF V600 mutation. Radiation therapy uses high energy rays to kill tumor cells and reduce the size of tumors. Dabrafenib and trametinib may stop the growth of tumor cells by blocking BRAF and MEK, respectively, which are enzymes that tumor cells need for their growth. Giving dabrafenib with trametinib after radiation therapy may work better than treatments used in the past in patients with newly-diagnosed BRAF V600-mutant high-grade glioma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Daniel Bowers
10760
All
12 Months to 21 Years old
Phase 2
NCT03919071
STU-2019-1457
Inclusion Criteria:
• PRE-ENROLLMENT ELIGIBILITY SCREENING (STEP 0): Patients must be >= 12 months and =< 21 years of age at the time of enrollment on Step 0
• Note: This age range encompasses pre-screening for all HGG patients. Individual treatment protocols may have different age criteria.
• PRE-ENROLLMENT ELIGIBILITY SCREENING (STEP 0): Patient is suspected of having localized newly-diagnosed HGG, excluding metastatic disease.
• PRE-ENROLLMENT ELIGIBILITY SCREENING (STEP 0): Patient and/or their parents or legal guardians have signed informed consent for eligibility screening on APEC14B1 Part A.
• PRE-ENROLLMENT ELIGIBILITY SCREENING (STEP 0): The specimens obtained at the time of diagnostic biopsy or surgery must be submitted through APEC14B1 as soon as possible (ASAP), preferably within 5 calendar days of the procedure.
• Please note: See the APEC14B1 Manual of Procedures for a full list of detailed instructions for submitting required materials and for shipping details.
• Patients must be >= 3 years and =< 21 years of age at the time of enrollment.
• Patients must have eligibility confirmed by Rapid Central Pathology and Molecular Screening Reviews performed on APEC14B1
• Newly diagnosed high-grade glioma with BRAF^V600-mutation
• Results for H3 K27M by immunohistochemistry (IHC) or sequencing
• Histologically confirmed high-grade glioma (World Health Organization [WHO] grade III or IV) including but not limited to: anaplastic astrocytoma (AA), anaplastic pleomorphic xanthoastrocytoma (aPXA), anaplastic gangliogliomas (aGG), glioblastoma (GB), and high-grade astrocytoma, not otherwise specified (NOS).
• Patients must have had histologic verification of a high-grade glioma diagnosis. CSF cytology by lumbar puncture must be done if clinically indicated and determined to be safe prior to study enrollment. If cytology proves positive, the patient would be considered to have metastatic disease and would, therefore, be ineligible.
• A pre- and post-operative brain MRI with and without contrast and a baseline spine MRI with contrast must be obtained prior to enrollment. The requirement for a post-operative MRI is waived for patients who undergo biopsy only. If the spine MRI is positive, the patient would be considered to have metastatic disease and would be ineligible.
• 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) >= 1000/uL (within 7 days prior to enrollment).
• Platelet count >= 100,000/uL (transfusion independent) (within 7 days prior to enrollment).
• Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (within 7 days prior to enrollment).
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 (within 7 days prior to enrollment) or
• A serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
• Age 3 to < 6 years (Male 0.8 mg/dL, Female 0.8 mg/dL)
• Age 6 to < 10 years (Male 1 mg/dL, Female 1 mg/dL)
• Age 10 to < 13 years (Male 1.2 mg/dL, Female 1.2 mg/dL)
• Age 13 to < 16 years (Male 1.5 mg/dL, Female 1.4 mg/dL)
• Age >= 16 years (Male 1.7 mg/dL, Female 1.4 mg/dL)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment), and
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L.
• Patients with a seizure disorder may be enrolled if their seizures are well controlled while on non-enzyme inducing anticonvulsants permitted on this study.
• All patients and/or their parents or legal guardians must sign a written informed consent
• Patients must be enrolled and protocol therapy must be projected to begin no later than 31 days after definitive surgery (day 0). If a biopsy only was performed, the biopsy date will be considered the date of definitive surgery. For patients who have a biopsy or incomplete resection at diagnosis followed by additional surgery, the date of the last resection will be considered the date of definitive surgery.
Exclusion Criteria:
• Patients with intrinsic brainstem or primary spinal cord tumors will be excluded.
• Patients with metastatic disease (defined as neuraxis dissemination either by imaging or by cytology) will be excluded.
• Patients must not have received any prior tumor-directed therapy including chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant for the treatment of HGG other than surgical intervention and/or corticosteroids.
• Previous treatment with dabrafenib or another RAF inhibitor, trametinib or another MEK inhibitor, or an ERK inhibitor.
• Patients with a history of a malignancy with confirmed activating RAS mutation.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to dabrafenib, trametinib, and their excipients.
• Uncontrolled medical conditions (e.g., diabetes mellitus, hypertension, liver disease, or uncontrolled infection), psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol; or unwillingness or inability to follow the procedures required in the protocol.
• Presence of active gastrointestinal (GI) disease or other condition (e.g., small bowel or large bowel resection) that will interfere significantly with the absorption of drugs.
• History of hepatitis B virus, or hepatitis C virus infection (patients with laboratory evidence of cleared hepatitis B virus and/or hepatitis C virus may be enrolled).
• History or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the study such as uncontrolled or significant cardiac disease, including any of the following:
• Recent myocardial infarction (within the last 6 months);
• Uncontrolled congestive heart failure;
• Unstable angina (within last 6 months);
• Clinically significant (symptomatic) or known, uncontrolled cardiac arrhythmias (e.g., sustained ventricular tachycardia, and clinically significant second or third degree atrioventricular [AV] block without a pacemaker) except sinus arrhythmia within the past 24 weeks prior to the first dose of study treatment;
• Coronary angioplasty or stenting (within last 6 months);
• Intra-cardiac defibrillators;
• Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram.
• Patients with a history or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR), or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension).
• Patients with presence of interstitial lung disease or pneumonitis.
• Female patients who are pregnant are ineligible since there is yet no available information regarding human fetal or teratogenic toxicities.
• Lactating females are not eligible unless they have agreed not to breastfeed their infants for the duration of the study and for 4 months following discontinuation of study therapy.
• Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained.
• Sexually active patients of reproductive potential (male or female) are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation and for 4 months following discontinuation of study therapy. Male patients (including those who have had a vasectomy) taking dabrafenib and trametinib combination therapy must use a condom during intercourse while on study and for 16 weeks after stopping treatment, and should not father a child during these periods. Women of childbearing potential should use effective non-hormonal contraception during therapy and for 4 weeks following discontinuation of dabrafenib and at least 4 months following the last dose of trametinib in patients taking combination therapy. Women should be advised that dabrafenib may decrease the efficacy of hormonal contraceptives and an alternate method of contraception, such as barrier methods, should be used.
Procedure: Biospecimen Collection, Drug: Dabrafenib Mesylate, Procedure: Lumbar Puncture, Procedure: Magnetic Resonance Imaging, Radiation: Radiation Therapy, Drug: Trametinib Dimethyl Sulfoxide
Glioblastoma, Malignant Glioma, Anaplastic Astrocytoma, Anaplastic Pleomorphic Xanthoastrocytoma, Anaplastic Ganglioglioma, Brain and Nervous System, WHO Grade 3 Glioma, Anaplastic Astrocytoma, Not Otherwise Specified
Children’s Health
A Study of Daratumumab Plus Lenalidomide Versus Lenalidomide Alone as Maintenance Treatment in Participants With Newly Diagnosed Multiple Myeloma Who Are Minimal Residual Disease Positive After Frontline Autologous Stem Cell Transplant (AURIGA)
The purpose of this study is to evaluate conversion rate to minimal residual disease (MRD) negativity following the addition of daratumumab to lenalidomide relative to lenalidomide alone, when administered as maintenance treatment to anti-cluster of differentiation 38 (CD38) treatment naive participants with newly diagnosed multiple myeloma who are MRD positive as determined by next generation sequencing (NGS) at screening, following high-dose therapy (HDT) and autologous stem cell transplant (ASCT).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Larry Anderson
102991
All
18 Years to 79 Years old
Phase 3
NCT03901963
STU-2019-1432
Inclusion Criteria:
• Must have newly diagnosed multiple myeloma with a history of a minimum of 4 cycles of induction therapy, have received high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) within 12 months of the start of induction therapy, and be within 6 months of ASCT on the date of randomization
• Must have a very good partial response (VGPR) or better response assessed per International Myeloma Working Group (IMWG) 2016 criteria at the time of randomization
• Must have archived bone marrow samples collected before induction treatment (that is, at diagnosis) or before transplant (for example, at the end of induction) or have existing results on the index multiple myeloma clone based on Adaptive Biotechnologies' next generation sequencing (NGS)-based minimal residual disease (MRD) assay. Archived bone marrow samples will be used for calibration of myeloma clonal cells to facilitate assessment of primary end point by NGS. If an existing result on index myeloma clone is available from Adaptive Biotechnologies' NGS-based MRD assay, as part of institutional procedures, an archived bone marrow sample is not required as long as Adaptive Biotechnologies is able to retrieve historical results on the index myeloma clone form the clinical database. Any one of the following archived samples are required: (a) Greater than 1 milliliter (mL) viable frozen bone marrow aspirated aliquot (preferred) collected in an ethylenediaminetetra-acetic acid (EDTA) tube, frozen, and stored at a temperature of -80 centigrade (°C), or; (b) Non-decalcified diagnostic bone marrow aspirate clot sections (block or slides) for MRD assessment: (i) A formalin fixed paraffin embedded (FFPE) block of bone marrow aspirate clot, or slides (preferably 5, if available), 5 micrometer each, of non-decalcified bone marrow, or; (ii) Slides (preferably 5, if available), bone marrow aspirate smear; (iii) Please note, bone marrow core sections are not acceptable samples for analysis; (iv) In exceptional circumstances when index myeloma clone cannot be identified from the archived bone marrow sample, a post-transplant sample can be used to identify myeloma clone with permission from the sponsor
• Must have residual disease as defined by detectable MRD (Adaptive Biotechnologies' NGS based MRD assay)
• Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
Exclusion Criteria:
• A history of malignancy (other than multiple myeloma) unless all treatment of that malignancy was completed at least 2 years before consent and the participant has no evidence of disease before the of date of randomization. Exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years
• Must not have progressed on multiple myeloma (MM) therapy at any time prior to screening
• Have had prior treatment/therapy with: (a) Daratumumab or any other anti-cluster of differentiation 38 (CD38) therapies, (b) Focal radiation therapy within 14 days prior to randomization with the exception of palliative radiotherapy for symptomatic management but not on measurable extramedullary plasmacytoma. Radiotherapy within 14 days prior to randomization on measurable extramedullary plasmacytoma is not permitted even in the setting of palliation for symptomatic management, or (c) Plasmapheresis within 28 days of randomization
• Be exhibiting clinical signs of meningeal or central nervous system involvement due to multiple myeloma
• Have known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) less than (<) 50 percent (%) of predicted normal
• Have known moderate or severe persistent asthma within the past 2 years or current uncontrolled asthma of any classification
• Have any of the following: (a) Known history of seropositivity for human immunodeficiency virus (HIV); (b) Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]. Participants with resolved infection (that is, participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Participants with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR; (c) Seropositive for hepatitis C (anti-hepatitis C virus [HCV] antibody positive or HCV-RNA quantitation positive), except in the setting of a sustained virologic response, defined as aviremia at least 12 weeks after completion of antiviral therapy)
Drug: Daratumumab, Drug: Lenalidomide
Multiple Myeloma
UT Southwestern
RejuvenAir® System Trial for COPD With Chronic Bronchitis (SPRAY-CB)
Chronic Obstructive Pulmonary Disease (COPD) is defined as an impaired ability to move air within the lungs and is a major public health problem that is projected to rank fifth worldwide in terms of disease burden and third in terms of mortality. Chronic bronchitis (CB) is a common clinical phenotype within the umbrella of a COPD diagnosis and is classically defined as chronic cough and sputum production for 3 months a year for 2 consecutive years2, but many studies have used different definitions to define it- chronic cough and sputum production for one year or cough and sputum production on most days of the week. CB is associated with multiple clinical consequences, including; the worsening of lung function decline, increasing risk of acute exacerbations of COPD, increased risk of developing pneumonia, reduced health related quality of life, and an increase in all-cause mortality.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Taelor.Dumond@UTSouthwestern.edu
Muhanned Abu-Hijleh
123140
All
40 Years to 80 Years old
N/A
NCT03893370
STU-2019-0896
Inclusion Criteria
• Males and females ≥40 to ≤80 years of age
• Subject is able to read, understand, and sign a written Informed Consent in order to participate in the Study
• Subject has a diagnosis of chronic bronchitis (CB) and/or chronic obstructive pulmonary disease (COPD) for a minimum of two years. (Chronic Bronchitis is defined clinically as chronic productive cough for 3 months in each of 2 successive years in a patient in whom other causes of productive cough have been excluded)
• Subject is classified as having a moderate or severe (GOLD 2/3) airflow obstruction defined by a post-bronchodilator of ≥30% FEV1 to <80% predicted with a baseline FEV1/FVC of <0.70
• Subject has a Baseline SGRQ of ≥50
• Subject demonstrates daily cough and significant mucus.
• Subject is being treated according to current medically accepted treatment guidelines for chronic bronchitis for minimum of 3 months prior to enrollment into the study. Subject agrees to continue maintenance pulmonary/COPD medications (GOLD standard medications recommended) for the duration of the study
• Non-smoking for a minimum of 2 months prior to consent and agrees to continue not smoking for the duration of the study
• Subject is able to adhere to and undergo 2 bronchoscopic procedures (cross over subjects may undergo two additional bronchoscopic procedures, if they agree to treatment), per hospital guidelines
• Subject demonstrates ability and willingness to use a daily eDiary Exclusion Criteria
• Subject has had an acute pulmonary infection, exacerbation or pneumonia requiring medical treatment (with antibiotics and/or steroids) within 4 weeks prior of initially planned study bronchoscopy
• Current diagnosis of Asthma
• Subject has Alpha-1 antitrypsin deficiency as defined by blood level <59 mg/dL
• Subject has other origins of respiratory disease aside from chronic bronchitis and COPD
• Subject is using e-cigarettes, vaping or taking any inhaled substances not prescribed by a physician
• Subject has untreatable or life threatening arrhythmias, inability to adequately oxygenate during the bronchoscopy, or has acute respiratory failure
• Subject has bullous emphysema characterized as large bullae >30 millimeters on HRCT; or subject has stenosis in the tracheobronchial system, tracheobronchomegaly, trachea-bronchomalacia, amyloidosis or cystic fibrosis
• Subject has clinically significant bronchiectasis
• Subject has had a solid transplant procedure
• Subject has a known mucosal tear, has undergone prior lung surgery such as pneumonectomy, lobectomy, bullectomy, or lung volume reduction surgery
• Subject has had a prior lung device procedure, including emphysema stent(s) implanted, lung coils, valves, lung denervation, bronchial thermoplasty, cryotherapy or other therapies
• Subject is unable to temporarily discontinue use of anticoagulant therapy: warfarin, Coumadin, LMWH, heparin, clopidrogel (or equal)
• Subject has a serious medical condition, such as: uncontrolled coagulopathy or bleeding disorder, congestive heart failure, uncontrolled angina, myocardial infarction in the past year, renal failure, liver disease, cerebrovascular accident within the past 6 months, uncontrolled diabetes, uncontrolled hypertension or uncontrolled gastric reflux
• Subject is pregnant, nursing, or planning to get pregnant during study duration
• Subject has or is receiving chemotherapy or active radiation therapy within the past 6 months or is expected to receive chemotherapy during participation in this study
• Subject is or has been in another treatment study within 6 weeks of enrollment and agrees to not participate in any other treatment studies for the duration of study participation
• Subject has known sensitivity to medication required to perform bronchoscopy (such as lidocaine, atropine, and benzodiazepines)
• Males and females ≥40 to ≤80 years of age
• Subject is able to read, understand, and sign a written Informed Consent in order to participate in the Study
• Subject has a diagnosis of chronic bronchitis (CB) and/or chronic obstructive pulmonary disease (COPD) for a minimum of two years. (Chronic Bronchitis is defined clinically as chronic productive cough for 3 months in each of 2 successive years in a patient in whom other causes of productive cough have been excluded)
• Subject is classified as having a moderate or severe (GOLD 2/3) airflow obstruction defined by a post-bronchodilator of ≥30% FEV1 to <80% predicted with a baseline FEV1/FVC of <0.70
• Subject has a Baseline SGRQ of ≥50
• Subject demonstrates daily cough and significant mucus.
• Subject is being treated according to current medically accepted treatment guidelines for chronic bronchitis for minimum of 3 months prior to enrollment into the study. Subject agrees to continue maintenance pulmonary/COPD medications (GOLD standard medications recommended) for the duration of the study
• Non-smoking for a minimum of 2 months prior to consent and agrees to continue not smoking for the duration of the study
• Subject is able to adhere to and undergo 2 bronchoscopic procedures (cross over subjects may undergo two additional bronchoscopic procedures, if they agree to treatment), per hospital guidelines
• Subject demonstrates ability and willingness to use a daily eDiary Exclusion Criteria
• Subject has had an acute pulmonary infection, exacerbation or pneumonia requiring medical treatment (with antibiotics and/or steroids) within 4 weeks prior of initially planned study bronchoscopy
• Current diagnosis of Asthma
• Subject has Alpha-1 antitrypsin deficiency as defined by blood level <59 mg/dL
• Subject has other origins of respiratory disease aside from chronic bronchitis and COPD
• Subject is using e-cigarettes, vaping or taking any inhaled substances not prescribed by a physician
• Subject has untreatable or life threatening arrhythmias, inability to adequately oxygenate during the bronchoscopy, or has acute respiratory failure
• Subject has bullous emphysema characterized as large bullae >30 millimeters on HRCT; or subject has stenosis in the tracheobronchial system, tracheobronchomegaly, trachea-bronchomalacia, amyloidosis or cystic fibrosis
• Subject has clinically significant bronchiectasis
• Subject has had a solid transplant procedure
• Subject has a known mucosal tear, has undergone prior lung surgery such as pneumonectomy, lobectomy, bullectomy, or lung volume reduction surgery
• Subject has had a prior lung device procedure, including emphysema stent(s) implanted, lung coils, valves, lung denervation, bronchial thermoplasty, cryotherapy or other therapies
• Subject is unable to temporarily discontinue use of anticoagulant therapy: warfarin, Coumadin, LMWH, heparin, clopidrogel (or equal)
• Subject has a serious medical condition, such as: uncontrolled coagulopathy or bleeding disorder, congestive heart failure, uncontrolled angina, myocardial infarction in the past year, renal failure, liver disease, cerebrovascular accident within the past 6 months, uncontrolled diabetes, uncontrolled hypertension or uncontrolled gastric reflux
• Subject is pregnant, nursing, or planning to get pregnant during study duration
• Subject has or is receiving chemotherapy or active radiation therapy within the past 6 months or is expected to receive chemotherapy during participation in this study
• Subject is or has been in another treatment study within 6 weeks of enrollment and agrees to not participate in any other treatment studies for the duration of study participation
• Subject has known sensitivity to medication required to perform bronchoscopy (such as lidocaine, atropine, and benzodiazepines)
Device: RejuvenAir System, Device: Sham Control Procedure
Chronic Bronchitis
UT Southwestern
A Study of the Drugs Selumetinib Versus Carboplatin/Vincristine in Patients With Neurofibromatosis and Low-Grade Glioma
This phase III trial studies if selumetinib works just as well as the standard treatment with carboplatin/vincristine (CV) for subjects with NF1-associated low grade glioma (LGG), and to see if selumetinib is better than CV in improving vision in subjects with LGG of the optic pathway (vision nerves). Selumetinib is a drug that works by blocking some enzymes that low-grade glioma tumor cells need for their growth. This results in killing tumor cells. Drugs used as chemotherapy, such as carboplatin and vincristine, 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. It is not yet known whether selumetinib works better in treating patients with NF1-associated low-grade glioma compared to standard therapy with carboplatin and vincristine.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Laura Klesse
13954
All
2 Years to 21 Years old
Phase 3
NCT03871257
STU-2019-1466
Inclusion Criteria:
• Patients must be >= 2 years and =< 21 years at the time of enrollment
• Patients must have a body surface area (BSA) of >= 0.5 m^2 at enrollment
• Patients must have neurofibromatosis type 1 (NF1) based on clinical criteria and/or germline genetic testing
• Patients must be newly diagnosed or have previously diagnosed NF-1 associated LGG that has not been treated with any modality other than surgery
• For patients with optic pathway gliomas (OPGs):
• Newly-diagnosed patients with OPG are eligible if there are neurologic symptoms (including visual dysfunction, as defined below) or other exam findings associated with the tumor
• Previously-diagnosed patients with OPG are eligible if they have new or worsening neurologic symptoms (including visual dysfunction, as defined below) or have tumor growth
• For both newly-diagnosed and previously-diagnosed OPG, the patient may be eligible, irrespective of whether there has been tumor growth or other neurological symptoms or worsening, if they meet at least one of the following visual criteria:
• Visual worsening, defined as worsening of visual acuity (VA) or visual fields (VF) documented within the past year (by examination or history); OR
• Significant visual dysfunction (defined as VA worse than normal for age by
• 6 logMAR [20/80, 6/24, or 2.5/10] or more in one or both eyes)
• For patients with LGG in other locations (i.e., not OPGs):
• Newly-diagnosed patients with LGG are eligible if there are neurologic symptoms or other exam findings associated with the tumor
• NOTE: Newly-diagnosed patients with LGG without associated neurologic symptoms or exam findings are not eligible
• Previously-diagnosed patients with LGG are eligible if they have new or worsening neurologic symptoms or have tumor growth
• Although not required, if a biopsy/tumor resection is performed, eligible histologies will include all tumors considered LGG or low-grade astrocytoma (World Health Organization [WHO] grade I and II) by 5th edition WHO classification of central nervous system (CNS) tumors with the exception of subependymal giant cell astrocytoma
• Patients must have two-dimensional measurable tumor >= 1 cm^2
• Patients with metastatic disease or multiple independent primary LGGs are allowed on study
• Creatinine clearance or radioisotope glomerular filtration Rate (GFR) >= 70 mL/min/1.73 m^2 OR a serum creatinine based on age/gender (within 7 days prior to enrollment) as follows:
• Age; maximum serum creatinine (mg/dL)
• 2 to < 6 years; 0.8 (male) and 0.8 (female)
• 6 to < 10 years; 1 (male) and 1 (female)
• 10 to < 13 years; 1.2 (male) and 1.2 (female)
• 13 to < 16 years; 1.5 (male) and 1.4 (female)
• >= 16 years; 1.7 (male) and 1.4 (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment) (children with a diagnosis of Gilbert's syndrome will be allowed on study regardless of their total and indirect [unconjugated] bilirubin levels as long as their direct [conjugated] bilirubin is < 3.1 mg/dL)
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x upper limit of normal (ULN) = 135 U/L (within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L
• Albumin >= 2 g/dL (within 7 days prior to enrollment)
• Left ventricular ejection fraction (LVEF) >= 53% (or institutional normal; if the LVEF result is given as a range of values, then the upper value of the range will be used) by echocardiogram (within 4 weeks prior to enrollment)
• Corrected QT (QTc) interval =< 450 msec by electrocardiography (EKG) (within 4 weeks prior to enrollment)
• Absolute neutrophil count >= 1,000/uL (unsupported) (within 7 days prior to enrollment)
• Platelets >= 100,000/uL (unsupported) (within 7 days prior to enrollment)
• Hemoglobin >= 8 g/dL (may be supported) (within 7 days prior to enrollment)
• Patients with a known seizure disorder should be stable and should have not experienced a significant increase in seizure frequency within 2 weeks prior to enrollment
• Patients 2-17 years of age must have a blood pressure that is =< 95th percentile for age, height, and gender at the time of enrollment. Patients >= 18 years of age must have a blood pressure =< 130/80 mmHg at the time of enrollment (with or without the use of antihypertensive medications).
• Note: Adequate blood pressure can be achieved using medication for the treatment of hypertension
• All patients must have ophthalmology toxicity assessments performed within 4 weeks prior to enrollment
• For all patients, an MRI of the brain (with orbital cuts for optic pathway tumors) and/or spine (depending on the site(s) of primary disease) with and without contrast must be performed within 4 weeks prior to enrollment
• For patients who undergo a surgery on the target tumor (not required), a pre- and post-operative* MRI of the brain (with orbital cuts for optic pathway tumors) or spine (depending on the site(s) of primary disease) with and without contrast must also be performed within 4 weeks prior to enrollment
• The post-operative MRIs should be performed ideally within 48 hours after surgery if possible
• 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
• Patients must have the ability to swallow whole capsules
• Patients must have receptive and expressive language skills in English or Spanish to complete the quality of life (QOL) and neurocognitive assessments
• 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 must not have received any prior tumor-directed therapy including chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant. Prior surgical intervention is permitted
• Patients with a concurrent malignancy or history of treatment (other than surgery) for another tumor within the last year are ineligible
• Patients may not be receiving any other investigational agents
• Patients with any serious medical or psychiatric illness/ condition, including substance use disorders likely in the judgement of the investigator to interfere or limit compliance with study requirements/treatment are not eligible
• Patients who, in the opinion of the investigator, are not able to comply with the study procedures are not eligible
• Female patients who are pregnant are not eligible 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 are not eligible
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for 12 weeks after stopping study therapy are not eligible
• Note: Women of child-bearing potential and males with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) should use effective methods of contraception for the duration of the study and for 12 weeks after stopping study therapy to avoid pregnancy and/or potential adverse effects on the developing embryo
• Cardiac conditions:
• Known genetic disorder that increases risk for coronary artery disease. Note: The presence of dyslipidemia in a family with a history of myocardial infarction is not in itself an exclusion unless there is a known genetic disorder documented
• Symptomatic heart failure
• New York Heart Association (NYHA) class II-IV prior or current cardiomyopathy
• Severe valvular heart disease
• History of atrial fibrillation
• Ophthalmologic conditions:
• Current or past history of central serous retinopathy
• Current or past history of retinal vein occlusion or retinal detachment
• Patients with uncontrolled glaucoma
• If checking pressure is clinically indicated, patients with intraocular pressure (IOP) > 22 mmHg or ULN adjusted by age are not eligible
• Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor, or strabismus) or longstanding orbito-temporal plexiform neurofibroma (PN), such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study
• Treatments and/or medications patient is receiving that would make her/him ineligible, such as:
• Supplementation with vitamin E greater than 100% of the daily recommended dose. Any multivitamin containing vitamin E must be stopped prior to study enrollment even if less than 100% of the daily recommended dosing for vitamin E
• Surgery within 2 weeks prior to enrollment, with the exception of surgical placement for vascular access or cerebrospinal fluid (CSF) diverting procedures such as endoscopic third ventriculostomy (ETV) and ventriculo-peritoneal (VP) shunt.
• Note: Patients must have healed from any prior surgery prior to enrollment
• Patients who have an uncontrolled infection are not eligible
Drug: Carboplatin, Procedure: Magnetic Resonance Imaging, Other: Quality-of-Life Assessment, Other: Questionnaire Administration, Drug: Selumetinib Sulfate, Drug: Vincristine Sulfate
Neurofibromatosis Type 1, Low Grade Glioma, Visual Pathway Glioma
Children’s Health
Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
This phase II trial studies how well cabozantinib works in combination with nivolumab and ipilimumab in treating patients with rare genitourinary (GU) tumors that that has spread from where it first started (primary site) to other places in the body. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib, nivolumab, and ipilimumab may work better in treating patients with genitourinary tumors that have no treatment options compared to giving cabozantinib, nivolumab, or ipilimumab alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Suzanne Cole
42296
All
18 Years and over
Phase 2
NCT03866382
STU-2019-1012
Inclusion Criteria:
• Metastatic disease defined as new or progressive lesions on cross-sectional imaging or bone scan. Patients must have at least:
• One measurable site of disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
• One bone lesion on bone scan (tec99 or sodium fluoride [NaF] PET/CT, CT or MRI) for the bone-only cohort.
• Histologically confirmed diagnosis of one of the following metastatic cohorts:
• Small cell/ neuroendocrine carcinoma of the bladder- All urothelial carcinomas with any amount of neuroendocrine differentiation (including small cell differentiation) will be included. If the tumor is purely neuroendocrine, metastasis from another site of origin should be clinically excluded
• Adenocarcinoma of the bladder, or urachal adenocarcinoma, or bladder/urethra clear cell adenocarcinoma - must be pure (per World Health Organization [WHO] definition), (i.e. urothelial carcinoma with glandular differentiation is not considered a pure adenocarcinoma
• Squamous cell carcinoma of the bladder - must be pure (i.e. urothelial carcinoma with squamous differentiation is not considered a pure squamous cell carcinoma)
• Plasmacytoid urothelial carcinoma - Tumor should show predominantly > or equal ~ 50% plasmacytoid histology (including all types of discohesive growth, such as tumors with signet-ring and/or rhabdoid features as well)
• Any penile cancer
• Sarcomatoid renal cell carcinoma - Tumor should be predominantly sarcomatoid ~ 50% (including rhabdoid differentiation) is also unclassified renal cell carcinomas (RCCs): all (assuming they are high grade with metastasis) malignant angiomyolipomas are allowed
• Sarcomatoid urothelial carcinoma - Tumor should show predominantly ~ 50% sarcomatoid differentiation
• Renal medullary carcinoma - Per WHO definition, ideally confirmed with immunostains
• Renal collecting duct carcinoma - Per WHO definition (medullary involvement, predominant tubular morphology, desmoplastic stromal reaction, high grade cytology, infiltrative growth pattern, and absence of other renal cell carcinoma subtype or urothelial carcinoma)
• Bone only urothelial carcinoma or other non-prostate GU tumor
• Urethra carcinoma- May be of any histology but if urothelial carcinoma then must be isolated to the urethra and not have metachronous or synchronous urothelial carcinoma of the bladder
• Other miscellaneous histologic variants of the urothelial carcinoma, such as, but not limited to : micropapillary (Tumor should show predominantly > or equal 50% micropapillary architecture), giant cell, lipid-rich, clear cell and nested variants (Tumor should predominantly > or equal 50% show these features), large cell neuroendocrine carcinoma, lymphoepithelioma-like carcinoma and mixed patterns will be considered, as well as small cell neuroendocrine prostate cancer (Only treatment-naïve primary small cell of prostate with any amount of small cell component allowed. Post-treatment small cell prostatic carcinomas are not allowed), Malignant testicular Sertoli or Leydig cell tumors, and papillary and chromophobe RCC
• Note: Translocation positive renal cell carcinoma patients are eligible. However, AREN1721 should be considered before this trial
• Hematoxylin and eosin (H&E) slides from diagnostic tumor tissue for retrospective central pathology review
• Patients may have received up to 2 systemic anti-cancer treatments or be treatment naive. Patients with small cell carcinoma should have received a platinum-based combination regimen either as neoadjuvant, adjuvant or first-line treatment). Patients in the bone-only cohort may be urothelial carcinoma histology but must receive standard cisplatin-based chemotherapy (if cisplatin-eligible)
• Age >= 18 years
• Patients must be able to swallow oral formulation of the tablets
• Karnofsky performance status >= 80%
• Absolute neutrophil count (ANC) >= 1,000/mcL
• Platelet count >= 75,000/mcL
• Total bilirubin =< 1.5 x upper limit of normal (ULN). For subjects with known Gilbert's disease or similar syndrome with slow conjugation of bilirubin, total bilirubin =< 3.0 mg/dL
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x institutional upper limit of normal (ULN) (or =< 5 x ULN for patients with liver metastases or Gilbert's disease)
• Creatinine =< 1.5 x upper limit of normal (ULN) OR creatinine clearance >= 40 mL/min/1.73 m^2 (calculated using the Chronic Kidney Disease Epidemiology [CKD-EPI] equation or Cockcroft-Gault formula) for patients with creatinine levels above institutional normal
• Hemoglobin >= 9 g/dL (transfusion of packed red blood cells [PRBCs] allowed)
• Serum albumin >= 3.2 g/dL
• Lipase and amylase =< 2.0 x ULN and no radiologic (on baseline anatomical imaging) or clinical evidence of pancreatitis
• Prior treatment with MET or VEGFR inhibitors is allowed. However, prior cabozantinib will not be allowed. Also, patients that have received both prior MET or VEGF and prior PD-1/PD-L1/CTLA-4 (sequentially or in combination) are also not allowed
• Prior treatment with any therapy on the PD-1/PD-L1 axis or anti- CTLA-4/CTLA-4 inhibitors is allowed, either in the perioperative or in the metastatic setting. However, patients that have received both prior MET or VEGF and prior PD-1/PD-L1/CTLA-4 (sequentially or in combination) are not allowed
• Human immunodeficiency virus (HIV)-positive patients are eligible if on stable dose of highly active antiretroviral therapy (HAART), no clinically significant drug-drug interactions are anticipated with the current HAART regimen, CD4 counts are greater than 350 and viral load is undetectable
• Patients with rheumatoid arthritis and other rheumatologic arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication only and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies etc. are eligible but should be considered for rheumatologic evaluation for the presence of target organ involvement and potential need for systemic treatment
• Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones or medications (e.g. thyroiditis managed with propylthiouracil [PTU] or methimazole) including physiologic oral corticosteroids are eligible
• Patients who have evidence of active or acute diverticulitis, intra-abdominal abscess, and gastrointestinal (GI) obstruction, within 12 months are not eligible
• Women of childbearing potential must have a negative pregnancy test =< 7 days prior to registration
• Women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Post menopause is defined as amenorrhea >= 12 consecutive months. Note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression or any other reversible reason
• Pregnant women may not participate in this study because with cabozantinib, nivolumab, and ipilimumab have 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 cabozantinib, nivolumab, and ipilimumab, breastfeeding should be discontinued if the mother is treated with these agents
• The patient has received no cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 2 weeks before the first dose of study treatment
• The patient has received no radiation therapy:
• To the lungs and mediastinum or abdomen within 4 weeks before the first dose of study treatment, or has ongoing complications, or is healing from prior radiation therapy
• To brain metastasis within 3 weeks for whole-brain radiotherapy (WBXRT), and 2 weeks for stereotactic body radiation therapy (SBRT) before the first dose of study treatment
• To the abdomen within 4 weeks before the first dose of study treatment, or has ongoing complications, or is healing from prior radiation therapy
• To any other site(s) within 2 weeks before the first dose of study treatment
• The patient has received no radionuclide treatment within 6 weeks of the first dose of study treatment
• The patient has received no prior treatment with a small molecule kinase inhibitor within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment
• The patient has received no prior treatment with hormonal therapy within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment. Subjects receiving gonadotropin-releasing hormone (GnRH) agonists and antagonists are allowed to participate
• The patient has not received any other type of investigational agent within 14 days before the first dose of study treatment
• The patient must have recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =< grade 1 from toxicity due to all prior therapies except alopecia, neuropathy and other non-clinically significant adverse events (AEs) defined as lab elevation with no associated symptoms or sequelae
• The patient may not have active brain metastases or epidural disease. Patients with brain metastases previously treated with whole brain radiation or radiosurgery who are asymptomatic and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible. Neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment. Baseline brain imaging with contrast-enhanced CT or MRI scans for subjects with known brain metastases is required to confirm eligibility
• No concomitant treatment with warfarin. Aspirin (up to 325 mg/day), thrombin or factor Xa inhibitors, low-dose warfarin (=< 1 mg/day), prophylactic and therapeutic low molecular weight heparin (LMWH) are permitted
• No chronic concomitant treatment with strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's wort) or strong CYP3A4 inhibitors
• Because the lists of these agents are constantly changing, it is important to regularly consult medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
• The patient has not experienced any of the following:
• Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment
• Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood per day within 1 months before the first dose of study treatment
• Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment
• The patient has no tumor invading any major blood vessels
• The patient has no evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib. Patients with rectal tumor masses are not eligible
• The patient has no uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders including:
• Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening.
• Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment
• The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before randomization. Note: if initial QTcF is found to be > 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed. If the average of these three consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regard
• Any history of congenital long QT syndrome
• Any of the following within 6 months before registration of study treatment:
• Unstable angina pectoris
• Clinically-significant cardiac arrhythmias (patients with atrial fibrillation are eligible)
• Stroke (including transient ischemic attack [TIA], or other ischemic event)
• Myocardial infarction
• Cardiomyopathy
• No significant gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:
• Any of the following that have not resolved within 28 days before the first dose of study treatment:
• Active peptic ulcer disease
• Acute diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or malabsorption syndrome
• None of the following within 2 years before the first dose of study treatment:
• Abdominal fistula or genitourinary fistula
• Gastrointestinal perforation
• Bowel obstruction or gastric outlet obstruction
• Intra-abdominal abscess. Note: Complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more than 2 years before the first dose of study treatment
• Disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement are not eligible
• No other clinically significant disorders such as:
• Severe active infection requiring IV systemic treatment within 14 days before the first dose of study treatment
• Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment
• History of organ or allogeneic stem cell transplant
• Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment (for asymptomatic patients with an elevated thyroid-stimulating hormone [TSH], thyroid replacement may be initiated if clinically indicated without delaying the start of study treatment)
• No history of major surgery as follows:
• Major surgery within 3 months of the first dose of cabozantinib; however, if there were no wound healing complications, patients with rapidly growing aggressive cancers, may start as soon as 6 weeks if wound has completely healed post-surgery
• Minor surgery within 1 month of the first dose of cabozantinib if there were no wound healing complications or within 3 months of the first dose of cabozantinib if there were wound complications excluding core biopsies and mediport placement
• Complete wound healing from prior surgery must be confirmed before the first dose of cabozantinib irrespective of the time from surgery
• No history of severe hypersensitivity reaction to any monoclonal antibody
• No evidence of active malignancy, requiring systemic treatment within 2 years of registration
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib, nivolumab, ipilimumab or other agents used in study
• No positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection. If HBV sAG is positive, subsequent ribonucleic acid (RNA) polymerase chain reaction (PCR) must be negative
• No patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. These include, but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease
Procedure: Bone Scan, Drug: Cabozantinib S-malate, Procedure: Computed Tomography, Biological: Ipilimumab, Procedure: Magnetic Resonance Imaging, Biological: Nivolumab, Procedure: Positron Emission Tomography
Bladder Adenocarcinoma, Papillary Renal Cell Carcinoma, Sarcomatoid Renal Cell Carcinoma, Bladder Mixed Adenocarcinoma, Bladder Squamous Cell Carcinoma, Chromophobe Renal Cell Carcinoma, Kidney Medullary Carcinoma, Large Cell Neuroendocrine Carcinoma, Metastatic Bladder Carcinoma, Metastatic Bladder Large Cell Neuroendocrine Carcinoma, Metastatic Bladder Squamous Cell Carcinoma, Metastatic Kidney Medullary Carcinoma, Metastatic Malignant Genitourinary System Neoplasm, Metastatic Penile Carcinoma, Metastatic Sarcomatoid Renal Cell Carcinoma, Stage IV Bladder Cancer AJCC v8, Stage IV Penile Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8, Stage IVB Prostate Cancer AJCC v8, Bladder Clear Cell Adenocarcinoma, Bladder Neuroendocrine Carcinoma, Collecting Duct Carcinoma, Metastatic Urethral Carcinoma, Stage IV Urethral Cancer AJCC v8, Urethral Clear Cell Adenocarcinoma, Bladder Small Cell Neuroendocrine Carcinoma, Metastatic Bladder Small Cell Neuroendocrine Carcinoma, Metastatic Prostate Small Cell Neuroendocrine Carcinoma, Invasive Bladder Giant Cell Urothelial Carcinoma, Invasive Bladder Lymphoepithelioma-Like Carcinoma, Invasive Bladder Nested Urothelial Carcinoma, Invasive Bladder Plasmacytoid Urothelial Carcinoma, Invasive Bladder Sarcomatoid Urothelial Carcinoma, Invasive Bladder Urothelial Carcinoma, Metastatic Bladder Clear Cell (Glycogen-Rich) Urothelial Carcinoma, Metastatic Bladder Lipid-Rich Urothelial Carcinoma, Metastatic Bladder Micropapillary Urothelial Carcinoma, Metastatic Bladder Plasmacytoid Urothelial Carcinoma, Metastatic Bladder Sarcomatoid Urothelial Carcinoma, Urachal Adenocarcinoma, Malignant Testicular Leydig Cell Tumor, Malignant Testicular Sertoli Cell Tumor, Metastatic Bladder Giant Cell Urothelial Carcinoma, Metastatic Chromophobe Renal Cell Carcinoma, Metastatic Papillary Renal Cell Carcinoma
UT Southwestern
Lung-MAP: A Master Screening Protocol for Previously-Treated Non-Small Cell Lung Cancer
This screening and multi-sub-study randomized phase II/III trial will establish a method for genomic screening of similar large cancer populations followed by assigning and accruing simultaneously to a multi-sub-study hybrid Master Protocol (Lung-MAP). The type of cancer trait (biomarker) will determine to which sub-study, within this protocol, a participant will be assigned to compare new targeted cancer therapy, designed to block the growth and spread of cancer, or combinations to standard of care therapy with the ultimate goal of being able to approve new targeted therapies in this setting. In addition, the protocol includes non-match sub-studies which will include all screened patients not eligible for any of the biomarker-driven sub-studies.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Sawsan Rashdan
171142
All
18 Years and over
Phase 2/Phase 3
NCT03851445
STU-2019-0578
• 1 Registration Step 0:
• Patients who need the fresh biopsy must also submit whole blood for ctDNA testing (see Section 15.3). These patients must be registered to Step 0 to obtain a patient ID number for the submission. Patients registered to Step 0 are not registered to the LUNGMAP protocol. To participate in LUNGMAP, patients must be registered to Step 1 after evaluation of patient eligibility, including tumor tissue adequacy, per protocol Section 5.1, Step
• Patients registered at Step 0 must use the same SWOG patient ID for registration at Step 1. Step 1:
• Patients must have pathologically proven non-small cell lung cancer (all histologic types) confirmed by tumor biopsy and/or fine-needle aspiration. Disease must be Stage IV as defined in Section 4.0, or recurrent. The primary diagnosis of non-small cell lung cancer should be established using the current WHO/IASLC-classification of Thoracic Malignancies. All histologies, including mixed, are allowed.
• Patients must either be eligible to be screened at progression on prior treatment or to be pre-screened prior to progression on current treatment. These criteria are:
• Screening at progression on prior treatment: To be eligible for screening at progression, patients must have received at least one line of systemic therapy for any stage of disease (Stages I-IV) and must have progressed during or following their most recent line of therapy.
• For patients whose prior systemic therapy was for Stage I-III disease only (i.e. patient has not received any treatment for Stage IV or recurrent disease), disease progression on platinum-based chemotherapy must have occurred within one year from the last date that patient received that therapy. For patients treated with consolidation anti-PD-1 or anti-PD-L1 therapy for Stage III disease, disease progression on consolidation anti-PD-1 or anti-PD-L1 therapy must have occurred within one year from the date or initiation of such therapy.
• For patients whose prior therapy was for Stage IV or recurrent disease, the patient must have received at least one line of a platinum-based chemotherapy regimen or anti-PD-1/PD-L1 therapy, alone or in combination (e.g. Nivolumab or Pembrolizumab).
• Pre-Screening prior to progression on current treatment: To be eligible for pre-screening, current treatment must be for Stage IV or recurrent disease and patient must have received at least one dose of the current regimen. Patients must have previously received or currently be receiving a platinum-based chemotherapy regimen or anti-PD-1/PD-L1 therapy, alone or in combination (e.g. Nivolumab or Pembrolizumab). Patients on first-line treatment are eligible upon receiving Cycle 1, Day 1 infusion. Note: Patients will not receive their sub-study assignment until they progress and the LUNGMAP Notice of Progression is submitted.
• Patients must have adequate tumor tissue available, defined as ≥ 20% tumor cells and ≥
• 2 mm3 tumor volume.
• The local interpreting pathologist must review the specimen.
• The pathologist must sign the LUNGMAP Local Pathology Review Form confirming tissue adequacy prior to Step 1 registration. Patients must agree to have this tissue submitted to Foundation Medicine for common broad platform CLIA biomarker profiling, PD-L1, and c-MET IHC (see Section 15.2). If archival tumor material is exhausted, then a new fresh tumor biopsy that is formalin-fixed and paraffin-embedded (FFPE) must be obtained. Patients who need the fresh biopsy must also submit whole peripheral blood for ctDNA testing. A tumor block or FFPE slides 4-5 microns thick must be submitted. Bone biopsies are not allowed. If FFPE slides are to be submitted, at least 12 unstained slides plus an H&E stained slide, or 13 unstained slides must be submitted. However, it is strongly recommended that 20 FFPE slides be submitted. Note: Previous next-generation DNA sequencing (NGS) will be repeated if done outside this study for sub-study assignment. Patients must agree to have any tissue that remains after testing retained for the use of sub-study Translational Medicine (TM) studies at the time of consent the patient is enrolled in.
• Patients with known EGFR sensitizing mutations, EGFR T790M mutation, ALK gene fusion, ROS 1 gene rearrangement, or BRAF V600E mutation are not eligible unless they have progressed following all standard of care targeted therapy. EGFR/ALK/ROS/BRAF testing is not required prior to Step 1 registration, as it is included in the Foundation One testing for screening/pre-screening.
• Patients must have Zubrod performance status 0-1 (see Section 10.2) documented within 28 days prior to Step 1 registration.
• Patients must be ≥ 18 years of age.
• Patients must also be offered participation in banking for future use of specimens as described in Section 15.0.
• Patients must be willing to provide prior smoking history as required on the LUNGMAP Onstudy Form.
• As a part of the OPEN registration process (see Section 13.4 for OPEN access instructions) the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.
• Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.
• U.S. patients who can complete the survey and the interview by telephone or email in English must be offered participation in the S1400GEN Survey Ancillary Study if local institution's policies allow participants to receive the Amazon gift card (see Sections 15.7 and 18.5). Patients at institutions that cannot offer the survey must still participate in the main study.
Drug: Screening Platform
Previously Treated Non-Small Cell Lung Cancer, Lung/Thoracic
UT Southwestern; Parkland Health & Hospital System
Stopping Tyrosine Kinase Inhibitors in Affecting Treatment-Free Remission in Patients With Chronic Phase Chronic Myeloid Leukemia
This phase II trial studies how stopping tyrosine kinase inhibitors will affect treatment-free remission in patients with chronic myeloid leukemia in chronic phase. When the level of disease is very low, it's called molecular remission. TKIs are a type of medication that help keep this level low. However, after being in molecular remission for a specific amount of time, it may not be necessary to take tyrosine kinase inhibitors. It is not yet known whether stopping tyrosine kinase inhibitors will help patients with chronic myeloid leukemia in chronic phase continue or re-achieve molecular remission.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
67555
All
up to 25 Years old
Phase 2
NCT03817398
STU-2019-1261
Inclusion Criteria:
• Patient must have been diagnosed with CML-CP at < 18 years of age.
• Patient must have histologic verification of CML-CP at original diagnosis
• Patient must be in molecular remission (MR) with a BCR-ABL1 level of =< 0.01% BCR-ABL1 as measured using the International Scale (IS) by RQ-PCR for >= 2 consecutive years at the time of enrollment
• Please note: The lab evaluating disease status and molecular response for this study must be College of American Pathology (CAP) and/or Clinical Laboratory Improvement Amendments (CLIA) certified (United States [US] only), sites in other countries must be certified by their accredited authorities. All labs must use the International Scale guidelines with a sensitivity of detection assay =< 0.01% BCR-ABL1 and be able to report results in =< 2 weeks
• Patient must have received any TKI for a minimum of 3 consecutive years at time of enrollment
• Patient agrees to discontinue TKI therapy
• REGULATORY REQUIREMENTS
• 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
• ELIGIBILITY FOR PATIENT-REPORTED OUTCOMES (PROs):
• Age >= 8 years at the time of enrollment
• Ability to understand English or Spanish
• Cognitive ability to complete instruments according to the primary team
• ELIGIBILITY FOR AAML18P1 NEUROCOGNITIVE STUDY:
• Patient must be 5 years or older at the time of enrollment
• English-, French- or Spanish-speaking
• No known history of neurodevelopmental disorder prior to diagnosis of CML (e.g., Down syndrome, Fragile X, William syndrome, mental retardation)
• No significant visual or motor impairment that would prevent computer use or recognition of visual test stimuli
Exclusion Criteria:
• Known T3151 mutation
• Additional clonal chromosomal abnormalities in Philadelphia chromosome (Ph) positive (+) cells at any time prior to enrollment that include "major route" abnormalities (second Ph, trisomy 8, isochromosome 17q, trisomy 19), complex karyotype or abnormalities of 3q26.2
• History of accelerated phase or blast crisis CML
• Female patients who are pregnant
• Lactating females are not eligible unless they have agreed not to breastfeed their infants
• Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
Procedure: Biospecimen Collection, Other: Drug Withdrawn, Other: Quality-of-Life Assessment, Other: Questionnaire Administration, Drug: Tyrosine Kinase Inhibitor
Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
UT Southwestern; Children’s Health
Nivolumab in Treating Patients With Autoimmune Disorders and Advanced, Metastatic, or Unresectable Cancer
This phase Ib trial studies the side effects of nivolumab and to see how well it works in treating patients with autoimmune disorders and cancer that has spread to other places in the body or cannot removed by surgery. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Hans Hammers
169573
All
18 Years and over
Phase 1
NCT03816345
STU-2021-0100
Inclusion Criteria:
• Patients can have either histologically confirmed malignancy that is radiologically evaluable and metastatic or unresectable, or have a malignancy for which a PD-1/PD-L1 inhibitor has been approved in the adjuvant setting. Eligible tumor types include solid tumors and malignancies in which there is known evidence of clinical activity for single agent PD-1 or PD-L1 antibodies. Nivolumab is Food and Drug Administration (FDA)-approved for the treatment of melanoma, non-small cell lung cancer (NSCLC), Merkel cell cancer, bladder cancer, renal cell carcinoma (RCC), gastric cancer, hepatocellular carcinoma (HCC), cervical cancer, head and neck cancer, Hodgkin lymphoma (HL), metastatic small cell lung cancer (SCLC), and any solid tumor with microsatellite instability (MSI)-high status confirmed. Patients with HL are eligible but must follow standard response criteria. Additional tumor types may be eligible on a case by case basis upon discussion with principal investigator (PI). Patients enrolling on the trial for adjuvant use will be restricted to those with histology for which a PD-1/PD-L1 inhibitor has been approved in the adjuvant setting including but not limited to NSCLC, melanoma, RCC, cervical cancer, and bladder cancer
• Patients who have previously received other forms of immunotherapy (high-dose [HD] IL-2, IFN, CTLA-4) are allowed. Patients must not have received cytokine immunotherapy for at least 4 weeks before nivolumab administration. Patients who have received prior anti-CTLA4 will be allowed and the washout period is 6 weeks
• Age >= 18 years; children are excluded from this study but may be eligible for future pediatric phase 1 combination trials
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Karnofsky >= 60)
• Life expectancy of greater than 12 weeks
• Leukocytes >= 1,000/mcL
• Absolute neutrophil count >= 500/mcL
• Platelets >= 50,000/mcL
• Total bilirubin =< 2 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 x institutional ULN or < 8 x institutional ULN for patients with liver metastases or an autoimmune disease that is contributing to the elevation of these values
• Creatinine ULN OR glomerular filtration rate (GFR) >= 30 mL/min (if using the Cockcroft-Gault formula)
• Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial
• If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated
• If history of hepatitis C virus (HCV) infection, must be treated with undetectable HCV viral load
• Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate central nervous system (CNS) specific treatment is not required and is unlikely to be required for at least 4 weeks (or scheduled assessment after the first cycle of treatment), and a risk-benefit analysis (discussion) by the patient and the investigator favors participation in the clinical trial
• The effects of nivolumab on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) 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 participation. WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 5 months after the last dose of investigational product. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of nivolumab. Women must not be breastfeeding. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men) do not require contraception. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL. These durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days, and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she (or the participating partner) should inform the treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document
• Patients with more than one autoimmune disease are eligible. The treating physician would determine which autoimmune disease is dominant and the patient would be treated under that specific cohort
Exclusion Criteria:
• Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (AEs) due to agents administered more than 4 weeks earlier have not resolved or stabilized. Palliative (limited-field) radiation therapy (RT) is permitted (2 week washout from start of treatment), if all of the following criteria are met:
• Repeat imaging demonstrates no new sites of bone metastases
• The lesion being considered for palliative radiation is not a target lesion
• Patients with prior therapy with an anti-PD-1 or anti-PD-L1
• Patients with prior allogeneic hematologic transplant
• Patients who are receiving any other anticancer investigational agents
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) bleeding, obstruction, and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study. For the IBD (UC and CD) cohort, an endoscopic assessment, disease activity index, and disease specific inclusion/exclusion criteria will substitute for these factors in determining eligibility with the exception of abdominal carcinomatosis, which should prompt further evaluation
Procedure: Biospecimen Collection, Biological: Nivolumab
Systemic Lupus Erythematosus, Lymphoma, Sarcoma, Multiple Myeloma, Multiple Sclerosis, Rheumatoid Arthritis, Ulcerative Colitis, Mycosis Fungoides, Dermatomyositis, Psoriasis, Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm, Crohn Disease, Psoriatic Arthritis, Hematopoietic and Lymphoid Cell Neoplasm, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Head and Neck, 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, Stomach, Thyroid, Urinary Bladder, Leukemia, Other, Hodgkins Lymphoma, Kaposis sarcoma, Leukemia, Not Otherwise Specified, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Non-Hodgkins Lymphoma, Other Hematopoietic, Small Intestine, Soft Tissue, Unknown Sites, Inflammatory Bowel Disease, Autoimmune Disease, Sjogren Syndrome, Systemic Scleroderma, Unresectable Malignant Solid Neoplasm
UT Southwestern
Testing Immunotherapy Versus Observation in Patients With HPV Throat Cancer
This phase III trials studies whether maintenance immunotherapy (nivolumab) following definitive treatment with radiation and chemotherapy (cisplatin) result in significant improvement in overall survival (time being alive) and progression-free survival (time being alive without cancer) for patients with intermediate risk human papillomavirus (HPV) positive oropharynx cancer (throat cancer) that has spread to nearby tissue or lymph nodes. Drugs used in chemotherapy such as cisplatin 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. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether chemotherapy and radiation therapy followed by maintenance nivolumab therapy works better than chemotherapy and radiation therapy alone in treating patients with HPV positive oropharyngeal cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Sher
156059
All
18 Years and over
Phase 2/Phase 3
NCT03811015
STU-2020-1000
Inclusion Criteria:
• STEP 1: Age >= 18 years
• STEP 1: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• STEP 1: Patients must have oropharynx cancer (American Joint Committee on Cancer [AJCC] 8) that is p16-positive by immunohistochemistry OR p16 equivocal by IHC and HPV positive by in situ hybridization with the following criteria: >= 10 pack-years, stage T1-2N2-N3 or T3-4N0-3 (less than 10 pack-years is considered a non-smoker) OR < 10 pack-years, stage T4N0-N3 or T1-3N2-3
• STEP 1: Patients must not have known hypersensitivity to nivolumab or compounds of similar chemical or biologic composition.
• STEP 1: Patients with a history of allergic reactions attributed to platinum-based chemotherapy agents are excluded.
• STEP 1: Patients must not have had prior systemic therapy, radiation treatment or surgery for p16 positive oropharyngeal squamous cell carcinoma (OPSCC).
• NOTE: Patients who had resection of T1 or T2 carcinoma with no radiation or chemotherapy are eligible if surgery was done 5 years prior to enrollment
• STEP 1: Patients must not have received previous irradiation for head and neck tumor, skull base, or brain tumors.
• STEP 1: Patients must not receive investigational agents within 4 weeks of enrollment or at any time while on study.
• STEP 1: Patients with evidence of distant metastases or leptomeningeal disease (LMD) are excluded.
• STEP 1: Patients with uncontrolled inter-current illnesses which in the opinion of the investigator will interfere with the ability to undergo therapy including chemotherapy are excluded.
• STEP 1: Patients with a history of prior or second malignancy are excluded, with the exception of curatively treated non-melanoma skin cancer, or curatively treated cervical cancer; additionally, patients curatively treated for malignancy who remain disease-free at > 2 years of follow up, are not excluded.
• STEP 1: Absolute neutrophil count (ANC) >= 1500/mm^3 (must be obtained =< 2 weeks prior to randomization).
• STEP 1: Hemoglobin (Hgb) >= 8.0 g/dL (must be obtained =< 2 weeks prior to randomization).
• STEP 1: Platelet count >= 100,000/mm^3 (must be obtained =< 2 weeks prior to randomization).
• STEP 1: Creatinine clearance of >= 60 ml/min (must be obtained =< 2 weeks prior to randomization). Creatinine clearance may be measured or calculated. If calculating, creatinine clearance, use the Cockcroft-Gault formula.
• STEP 1: Total bilirubin within 1.5 times the normal limits (must be obtained =< 2 weeks prior to randomization).
• STEP 1: Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) within 2.0 times the normal limits (must be obtained =< 2 weeks prior to randomization).
• STEP 1: Alkaline phosphatase within 2.0 times the normal limits (must be obtained =< 2 weeks prior to randomization).
• STEP 1: Patients must not be pregnant or breast-feeding as chemotherapy, radiation, and immunotherapy may have possible teratogenicity effects; in addition, complications from pregnancy may interfere with the ability of patients to have an uninterrupted therapy. All patients of childbearing potential must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy. A patient of childbearing potential is any female, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
• STEP 1: Patients of childbearing potential must use an accepted and effective method of contraception or abstain from sexual intercourse for at least one week prior to the start of treatment, and continue for 5 months after the last dose of protocol treatment. Patients must also not donate ova during this same time period.
• STEP 1: Patients must have measurable disease
• STEP 1: Patients must have tumor measurements with CT of neck and CT of chest (or CT of neck and FDG PET/CT if standard of care) within 4 weeks prior to Step 1 randomization.
• STEP 1: Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue disease, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease. Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.
• STEP 1: Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event).
• STEP 1: Patients must not have a condition requiring systemic treatment with either corticosteroids (> 10 mg/day prednisone equivalents) or other immunosuppressive medications which are expected to continue during nivolumab administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg/day prednisone equivalents are permitted in the absence of active autoimmune disease
• STEP 1: Patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• STEP 1: 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
• STEP 1: Patients with a known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) must have no detectable viral load on a stable antiviral regimen
• STEP 1: Patients must not be receiving any other investigational agents.
• STEP 1: Patient must not have a baseline clinically significant hearing loss, which in the opinion of the investigator would preclude the use of cisplatin
• STEP 2: Patients must have progression per RECIST criteria AND tissue-proven progression on Arm B treatment within 12 months after completion of radiation therapy.
• STEP 2: ECOG performance status of 0 or 1.
• STEP 2: Patients must not have known hypersensitivity to nivolumab or compounds of similar chemical or biologic composition.
• STEP 2: Patients must not have received non-protocol anti-cancer therapy after completion of radiation and chemotherapy.
• STEP 2: ANC >= 1500/mm^3 (must be obtained =< 2 weeks prior to registration).
• STEP 2: Hgb >= 8.0 g/dL (must be obtained =< 2 weeks prior to registration).
• STEP 2: Platelet count >= 100,000/mm^3 (must be obtained =< 2 weeks prior to registration).
• STEP 2: Creatinine within institutional limits of normal (must be obtained =< 2 weeks prior to registration)
• STEP 2: Total bilirubin within 1.5 times the normal limits (must be obtained =< 2 weeks prior to registration).
• STEP 2: SGOT (AST) or SGPT (ALT) within 2.0 times the normal limits (must be obtained =< 2 weeks prior to registration).
• STEP 2: Alkaline phosphatase within 1.5 times the normal limits (must be obtained =< 2 weeks prior to registration).
• STEP 2: Patients must not be pregnant or breast-feeding as chemotherapy, radiation, and immunotherapy may have possible teratogenicity effects; in addition, complications from pregnancy may interfere with the ability of patients to have an uninterrupted therapy. All women of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy. A women of childbearing potential is any female, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
• STEP 2: Patients of childbearing potential must use an accepted and effective method of contraception or abstain from sexual intercourse for at least one week prior to the start of treatment, and continue for 5 months after the last dose of protocol treatment. Patients must also not donate ova during this same time period.
• STEP 2: Patients must have measurable disease at the time of documented progression
• NOTE: For patients that have undergone salvage surgery for disease recurrence, measurable disease is not required at the time of registration to Step 2
• STEP 2: Patients must have tumor measurements with CT of neck and CT of chest (or CT of neck and FDG PET/CT if standard of care) within 4 weeks prior to Step 2 registration
• NOTE: Patients that have undergone salvage surgery for disease recurrence prior to Step 2 are not required to have measurable disease post-resection, but must have CT of neck and CT of chest (or CT of neck and FDG PET/CT if standard of care) after salvage surgery and within 4 weeks prior to step 2 registration to establish a baseline prior to nivolumab
Drug: Cisplatin, Radiation: Intensity-Modulated Radiation Therapy, Biological: Nivolumab, Other: Patient Observation
Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Pathologic Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Pathologic Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
UT Southwestern; Parkland Health & Hospital System
Phase 2 Study of TVB-2640 in KRAS Non-Small Cell Lung Carcinomas
This is a prospective one-arm, two-stage phase 2 trial of TVB-2640 in KRAS mutant NSCLC patients. 13 patients will be treated with a minimum of 1 cycle of TVB-2640 therapy over 8 weeks.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Gerber
53487
All
18 Years and over
Phase 2
NCT03808558
STU 022017-058
Inclusion:
• Metastatic or advanced stage, histologically or cytologically confirmed NSCLC and molecular identification of oncogenic KRAS mutation.
• KRAS mutant NSCLC must be refractory, relapsed, and previously treated with doublet chemotherapy and immune checkpoint inhibitor (unless there is a specific contraindication to checkpoint inhibitor).
• Molecular characterization (tissue- or blood-based [ie, cell-free/circulating tumor DNA]) must have been performed and must have demonstrated an oncogenic KRAS mutation (e.g., exon 12, 13, 61, or 117 mutation detected by sequencing) by a CLIA-certified assay (source documentation required). KRAS mutations at other codons require review and approval by Study Chair.
• Subjects' EGFR mutation and ALK gene rearrangement status must be known prior to study entry. Subjects with EGFR mutation or ALK gene rearrangement must have progressed after appropriate FDA-approved targeted therapy options prior to eligibility.
• Patient has evidence of disease progression on most recent line of therapy.
• Patient has measurable disease by RECIST v1.1 (Eisenhauer, 2009).
• Age ≥ 18 years.
• ECOG performance status of 0 or 1.
• Predicted life expectancy of >3 months.
• Adequate organ and marrow function as defined below:
• absolute neutrophil count ≥ 1,500/mcL
• platelets ≥ 75,000/mcL
• total bilirubin <2X institutional upper limit of normal
• AST and ALT ≤5X institutional upper limit of normal
• serum creatinine <1.5X institutional upper limit of normal
• LVEF >50%
• QTcF <470msec
• 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, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• No significant ischemic heart disease or myocardial infarction within 6 months of first dose of TVB-2640 and with current adequate cardiac function as in 3.1.8.
• Ability to understand and the willingness to sign a written informed consent. Exclusion:
• Patient is unable to swallow oral medications or has impairment of GI function or GI disease that may significantly alter drug absorption such as active inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome.
• Patient has a history of risk factors for torsade de pointes such as uncontrolled heart failure, severe hypokalemia with potassium less than 3mM/L, history of long QT syndrome or require use during study participation of concomitant medications known to prolong QT/QTc interval.
• Patients who require use of strong CYP3A4/5 agonists or inhibitors during study participation.
• Patient has uncontrolled or severe intercurrent medical condition including uncontrolled brain metastases. Patients with stable brain metastases either treated or untreated, on a stable dose of steroids/anticonvulsants, with no dose increase within 4 weeks before the first dose of TVB-2640, and no anticipated dose change, are allowed.
• Patient underwent major surgery within 4 weeks before the first dose of TVB-2640 or received cancer-directed therapy either chemotherapy, radiotherapy, hormonal therapy, biologic or immunotherapy, etc. or an investigational drug or device within 2 weeks (6 weeks for mitomycin C and nitrosoureas) or 5 half-lives of that agent, whichever is shorter before the first dose of TVB-2640. In addition, any drug- related toxicity, with the exception of alopecia, an endocrinopathy controlled with replacement therapy, or a clinically stable toxicity not expected to increase from study therapy (eg, cisplatin-associated ototoxicity) should have recovered to • If female, patient is pregnant or breast-feeding.
• Patient has evidence of a serious active infection-infection requiring treatment with intravenous antibiotics.
• Patient has known immunodeficiency virus-HIV or hepatitis B or C infection, as such patients may be at increased risk for toxicity due to concomitant treatment and disease-related symptoms may preclude accurate assessment of the safety of TVB-2640.
• Patient has an important medical illness or abnormal laboratory finding that, in the Investigator's opinion, would increase the risk of participating in this study.
• Patients with prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational agent.
• History of clinically significant dry eye (xerophthalmia) or other corneal abnormality or, if a contact lens wearer, does not agree to abstain from contact lens use from baseline through the last study drug dose.
• Patient has a known allergy or hypersensitivity to components of TVB-2640.
• Patient has a prior history of hypersensitivity, drug/radiation-induced, or other immune-mediated pneumonitis.
• Metastatic or advanced stage, histologically or cytologically confirmed NSCLC and molecular identification of oncogenic KRAS mutation.
• KRAS mutant NSCLC must be refractory, relapsed, and previously treated with doublet chemotherapy and immune checkpoint inhibitor (unless there is a specific contraindication to checkpoint inhibitor).
• Molecular characterization (tissue- or blood-based [ie, cell-free/circulating tumor DNA]) must have been performed and must have demonstrated an oncogenic KRAS mutation (e.g., exon 12, 13, 61, or 117 mutation detected by sequencing) by a CLIA-certified assay (source documentation required). KRAS mutations at other codons require review and approval by Study Chair.
• Subjects' EGFR mutation and ALK gene rearrangement status must be known prior to study entry. Subjects with EGFR mutation or ALK gene rearrangement must have progressed after appropriate FDA-approved targeted therapy options prior to eligibility.
• Patient has evidence of disease progression on most recent line of therapy.
• Patient has measurable disease by RECIST v1.1 (Eisenhauer, 2009).
• Age ≥ 18 years.
• ECOG performance status of 0 or 1.
• Predicted life expectancy of >3 months.
• Adequate organ and marrow function as defined below:
• absolute neutrophil count ≥ 1,500/mcL
• platelets ≥ 75,000/mcL
• total bilirubin <2X institutional upper limit of normal
• AST and ALT ≤5X institutional upper limit of normal
• serum creatinine <1.5X institutional upper limit of normal
• LVEF >50%
• QTcF <470msec
• 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, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• No significant ischemic heart disease or myocardial infarction within 6 months of first dose of TVB-2640 and with current adequate cardiac function as in 3.1.8.
• Ability to understand and the willingness to sign a written informed consent. Exclusion:
• Patient is unable to swallow oral medications or has impairment of GI function or GI disease that may significantly alter drug absorption such as active inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome.
• Patient has a history of risk factors for torsade de pointes such as uncontrolled heart failure, severe hypokalemia with potassium less than 3mM/L, history of long QT syndrome or require use during study participation of concomitant medications known to prolong QT/QTc interval.
• Patients who require use of strong CYP3A4/5 agonists or inhibitors during study participation.
• Patient has uncontrolled or severe intercurrent medical condition including uncontrolled brain metastases. Patients with stable brain metastases either treated or untreated, on a stable dose of steroids/anticonvulsants, with no dose increase within 4 weeks before the first dose of TVB-2640, and no anticipated dose change, are allowed.
• Patient underwent major surgery within 4 weeks before the first dose of TVB-2640 or received cancer-directed therapy either chemotherapy, radiotherapy, hormonal therapy, biologic or immunotherapy, etc. or an investigational drug or device within 2 weeks (6 weeks for mitomycin C and nitrosoureas) or 5 half-lives of that agent, whichever is shorter before the first dose of TVB-2640. In addition, any drug- related toxicity, with the exception of alopecia, an endocrinopathy controlled with replacement therapy, or a clinically stable toxicity not expected to increase from study therapy (eg, cisplatin-associated ototoxicity) should have recovered to
• Patient has evidence of a serious active infection-infection requiring treatment with intravenous antibiotics.
• Patient has known immunodeficiency virus-HIV or hepatitis B or C infection, as such patients may be at increased risk for toxicity due to concomitant treatment and disease-related symptoms may preclude accurate assessment of the safety of TVB-2640.
• Patient has an important medical illness or abnormal laboratory finding that, in the Investigator's opinion, would increase the risk of participating in this study.
• Patients with prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational agent.
• History of clinically significant dry eye (xerophthalmia) or other corneal abnormality or, if a contact lens wearer, does not agree to abstain from contact lens use from baseline through the last study drug dose.
• Patient has a known allergy or hypersensitivity to components of TVB-2640.
• Patient has a prior history of hypersensitivity, drug/radiation-induced, or other immune-mediated pneumonitis.
Drug: TVB-2640
KRAS Gene Mutation
UT Southwestern
Irinotecan Hydrochloride, Temozolomide, and Dinutuximab With or Without Eflornithine in Treating Patients With Relapsed or Refractory Neuroblastoma
This phase II trial studies how well irinotecan hydrochloride, temozolomide, and dinutuximab work with or without eflornithine in treating patients with neuroblastoma that has come back (relapsed) or that isn't responding to treatment (refractory). Drugs used in chemotherapy, such as irinotecan hydrochloride and temozolomide, 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 dinutuximab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Eflornithine blocks the production of chemicals called polyamines that are important in the growth of cancer cells. Giving eflornithine with irinotecan hydrochloride, temozolomide, and dinutuximab, may work better in treating patients with relapsed or refractory neuroblastoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tanya Watt
128737
All
1 Year and over
Phase 2
NCT03794349
STU-2019-1024
Inclusion Criteria:
• Patients must have had histologic verification of neuroblastoma or ganglioneuroblastoma or demonstration of neuroblastoma cells in the bone marrow with elevated urinary catecholamines (i.e. > 2 x upper limit of normal [ULN]), at the time of initial diagnosis.
• For the purposes of this study, aggressive multidrug chemotherapy is defined as chemotherapy including 2 or more agents that must include an alkylating agent and a platinum-containing compound as intended to treat high-risk disease. The doses of chemotherapy must be comparable to those used in frontline high-risk neuroblastoma therapies (examples include A3973, ANBL0532, ANBL09P1, ANBL12P1, and ANBL1531). Patients must have ONE of the following:
• First episode of recurrent high-risk disease following completion of aggressive multi-drug frontline high-risk therapy.
• First episode of progressive high-risk disease during aggressive multi-drug frontline therapy.
• Primary resistant/refractory disease (less than partial response by International Neuroblastoma Response Criteria [INRC]) detected at the conclusion of at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol (examples include A3973, ANBL0532, ANBL09P1, ANBL12P1, ANBL1531, etc.).
• Patients must have at least ONE of the following at the time of enrollment:
• Measurable tumor on magnetic resonance imaging (MRI) or computed tomography (CT) scan. Measurable is defined as >= 10 mm in at least one dimension on spiral/helical CT that is metaiodobenzylguanidine (MIBG) avid or demonstrates increased fludeoxyglucose F-18 (FDG) uptake on positron emission tomography (PET) scan.
• MIBG-avid lesion detected on MIBG scan with positive uptake at a minimum of one site. This site must represent disease recurrence after completion of therapy, progressive disease on therapy, or refractory disease during induction.
• Patients with resistant/refractory soft tissue disease that is not MIBG avid or does not demonstrate increased FDG uptake on PET scan must undergo biopsy to document the presence of viable neuroblastoma. Biopsy is not required for patients who have a new site of soft tissue disease (radiographic evidence of disease progression) regardless of whether progression occurs while receiving therapy or after completion of therapy.
• Patients with bone marrow disease only will be eligible if they have more than 5% disease involvement (documented neuroblastoma cells) in at least one sample from bilateral bone marrow biopsies.
• Note: Patients with elevated catecholamines (i.e. > 2 x ULN) only are NOT eligible for this study.
• 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.
• Primary refractory/resistant patients must have received at least 4 cycles of frontline high-risk chemotherapy. Frontline therapy may also have included surgery, chemotherapy, autologous stem cell transplantation (SCT) +/- MIBG, immunotherapy, radiotherapy, and retinoids but must NOT have received second line therapy for resistant/refractory, relapsed, or progressive disease. Patients who received intensified therapy for poor induction response or refractory disease (e.g. MIBG) will be considered to have received second line therapy and will not be eligible.
• At least 14 days must have elapsed since completion of myelosuppressive therapy.
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent.
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1.
• No interim time prior to study entry is required following prior radiation therapy (RT) for non-target lesions. However, patients must not have received radiation for a minimum of 4 weeks prior to study entry at the site of any lesion that will be identified as a target lesion to measure tumor response. Lesions that have been previously radiated cannot be used as target lesions unless there is radiographic evidence of progression at the site following radiation or a biopsy done following radiation shows viable neuroblastoma. Palliative radiation while on study is not permitted.
• Patients are eligible >= 6 weeks after autologous stem cell transplants or stem cell infusions (including stem cell infusions given as supportive care following 131 I-MIBG therapy) as long as hematologic and other eligibility criteria have been met.
• Patients are eligible >= 6 weeks after therapeutic 131 I-MIBG provided that all other eligibility criteria are met.
• Subjects who have previously received anti-GD2 monoclonal antibodies with or without retinoids for biologic therapy are eligible unless they have had progressive disease while receiving prior anti-GD2 therapy or progressed/relapsed within 3 months of receiving anti-GD2 therapy. However, eligible patients may NOT have received anti-GD2 monoclonal antibodies in combination with chemotherapy.
• Subjects who have received autologous marrow infusions or autologous stem cell infusions that were purged using monoclonal antibody linked to beads are eligible.
• Subjects who have previously received DFMO are eligible for this study provided they have not had progressive disease while receiving DFMO or progressed/relapsed within 3 months of completing DFMO.
• Patients must not have received long-acting myeloid growth factors (e.g. pegfilgrastim) within 14 days of entry on this study. Seven days must have elapsed since administration of a short-acting myeloid growth factor.
• For patients with solid tumors (without marrow involvement) including status post SCT: peripheral absolute neutrophil count (ANC) >= 750/uL (within 7 days prior to enrollment).
• For patients with solid tumors (without marrow involvement) including status post SCT: platelet count >= 75,000/uL (transfusion independent) (within 7 days prior to enrollment).
• Patients known to have bone marrow involvement with neuroblastoma are eligible provided that minimum ANC and transfusion independent platelet count criteria are met (as above). However, these patients are not evaluable for hematological toxicity.
• Creatinine clearance or radioisotope GFR >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• 1 to < 2 years (male 0.6 mg/dL, female 0.6 mg/dL)
• 2 to < 6 years (male 0.8 mg/dL, female 0.8 mg/dL)
• 6 to < 10 years (male 1 mg/dL, female 1 mg/dL)
• 10 to < 13 years (male 1.2 mg/dL, female 1.2 mg/dL)
• 13 to < 16 years (male 1.5 mg/dL, female 1.4 mg/dL)
• >= 16 years (male 1.7 mg/dL, female 1.4 mg/dL) (within 7 days prior to enrollment).
• Total bilirubin =< 1.5 x ULN for age (within 7 days prior to enrollment).
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 5.0 x ULN for age (=< 225 U/L). For the purpose of this study, the ULN for SGPT is 45 U/L (within 7 days prior to enrollment).
• Shortening fraction of >= 27% by echocardiography (ECHO) (within 7 days prior to enrollment).
• Ejection fraction of >= 50% by ECHO or gated radionuclide study (within 7 days prior to enrollment).
• No evidence of dyspnea at rest, no exercise intolerance, no chronic oxygen requirement, and room air pulse oximetry > 94% if there is a clinical indication for pulse oximetry. Normal pulmonary function tests in patients who are capable of cooperating with testing (including diffusion capacity of the lung for carbon monoxide [DLCO)] are required if there is a clinical indication for determination. For patients who do not have respiratory symptoms, full pulmonary function tests (PFTs) are NOT required.
• Patients with a history of central nervous system (CNS) disease must have no clinical or radiological evidence of active CNS disease at the time of study enrollment.
• Patients with seizure disorders may be enrolled if seizures are well controlled on anti-convulsants.
• CNS toxicity =< grade 2.
Exclusion Criteria:
• Men and women of childbearing potential and their partners must agree to use adequate contraception while enrolled on this study. Based on the established teratogenic potential of alkylating agents, pregnant women will be excluded from this study. Because of potential risks to breastfed infants due to drug metabolites that could be excreted in breast milk, female patients who are lactating must agree to stop breastfeeding or will otherwise be excluded from this study. Females of childbearing potential must have a negative pregnancy test to be eligible for this study.
• Patients with only elevated catecholamines (i.e. > 2 x ULN) are NOT eligible for this study.
• Patients must have been off pharmacologic doses of systemic steroids for at least 7 days prior to enrollment. Patients who require or are likely to require pharmacologic doses of systemic corticosteroids while receiving treatment on this study are ineligible. The only exception is for patients known to require 2 mg/kg or less of hydrocortisone (or an equivalent dose of an alternative corticosteroid) as premedication for blood product administration in order to avoid allergic transfusion reactions. The use of conventional doses of inhaled steroids for the treatment of asthma is permitted, as is the use of physiologic doses of steroids for patients with known adrenal insufficiency. Patients on any other immunosuppressive medications (e.g. cyclosporine, tacrolimus) are not eligible.
• Patients must not have received prior treatment with irinotecan and temozolomide.
• Patients must not have received enzyme-inducing anticonvulsants including phenytoin, phenobarbital, or carbamazepine for at least 7 days prior to study enrollment. Patients receiving non-enzyme inducing anticonvulsants such as gabapentin, valproic acid, or levetiracetam will be eligible.
• Patients who have received drugs that are strong inducers or inhibitors of CYP3A4 within 7 days prior to study enrollment are not eligible.
• Patients must not have been diagnosed with myelodysplastic syndrome or with any malignancy other than neuroblastoma.
• Patients with symptoms of congestive heart failure are not eligible.
• Patients must not have >= grade 2 diarrhea.
• Patients who are unable to tolerate oral/nasogastric/gastrostomy medications will not be eligible for this trial. Additionally, patients with significant malabsorption will not be eligible for this trial.
• Patients must not have uncontrolled infection.
• Patients with a history of grade 4 allergic reactions to anti-GD2 antibodies or reactions that required permanent discontinuation of the anti-GD2 therapy are not eligible.
• Patients with a significant intercurrent illness (any ongoing serious medical problem unrelated to cancer or its treatment) that is not covered by the detailed exclusion criteria and that is expected to interfere with the action of study agents or to significantly increase the severity of the toxicities experienced from study treatment are not eligible.
Biological: Dinutuximab, Drug: Eflornithine Hydrochloride, Drug: Irinotecan Hydrochloride, Biological: Sargramostim, Drug: Temozolomide
Recurrent Neuroblastoma, Refractory Neuroblastoma, High Risk Neuroblastoma
Children’s Health