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16 Study Matches
A Study of Amivantamab in Addition to Standard of Care Agents (SOC) Compared With SOC Alone in Participants With Recurrent/Metastatic Head and Neck Cancer (OrigAMI-5)
The purpose of this study is to compare anti-tumor activity of amivantamab in addition to pembrolizumab and carboplatin versus pembrolizumab, 5-fluorouracil (FU), and platinum therapy (carboplatin or cisplatin) in participants with refractory/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). HNSCC is a type of cancer that develops in the head and neck regions, including the outer tissue layer of the mouth and throat. This study will focus on participants with HNSCC who are treatment-naive (have not received prior treatment) in the R/M setting.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yu Cao
ALL
18 Years to old
PHASE3
NCT07276399
STU20260092
Inclusion criteria:
* Be more than or equal to (\>=) 18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place, whichever is greater)
* Have histologically or cytologically confirmed recurrent/metastatic (R/M) HNSCC that is considered incurable by local therapies: a. eligible primary tumor locations are the oral cavity, oropharynx, hypopharynx, or larynx; b. Must not have a primary tumor site of nasopharynx or primary tumor of unknown location; c. Must have documented local testing results per local regulations; d. Human papillomavirus (HPV) status must be known for participants with primary tumor location in oropharynx via p16 test, HPV DNA test, or high-risk HPV in situ hybridization (ISH). Any known p16, HPV DNA, or high-risk HPV ISH status of tumor must be negative
* Be treatment-naive for systemic therapy in the R/M setting
* Have an ECOG performance status of 0 or 1
* Have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v).1.1
Exclusion criteria:
* Have an uncontrolled illness
* Have untreated brain metastases or history of known presence of leptomeningeal disease
* Have a history of clinically significant cardiovascular disease
* Inadequate organ or bone marrow function
* Known allergies, hypersensitivity, contraindications, or intolerance to excipients of: Amivantamab, Pembrolizumab, Carboplatin, Cisplatin, 5-FU and Hyaluronidase
BIOLOGICAL: Amivantamab, BIOLOGICAL: Pembrolizumab, DRUG: Carboplatin, DRUG: 5-Flurouracil, DRUG: Cisplatin
Squamous Cell Carcinoma of Head and Neck, Larynx, Lip, Oral Cavity and Pharynx
UT Southwestern
ASPEN-09-03: A Study of Evorpacept in Combination With Trastuzumab and Chemotherapy in Metastatic HER2-Positive Breast Cancer (ASPEN-09-03)
The Substudy Protocol ASPEN-09-03 is a Phase 2, single-arm, multicenter study evaluating the efficacy, safety, and tolerability of evorpacept in combination with trastuzumab and chemotherapy in participants with HER2-positive metastatic breast cancer who have previously received trastuzumab-deruxtecan. This substudy is actively recruiting. ASPEN-09-03 is a substudy under Master Protocol ASPEN-09, and additional substudies are as follows: * Metastatic colorectal cancer (CRC) - dose escalation phase to evaluate evorpacept in combination with other drugs. This substudy is not open. * Recurrent/metastatic head and neck cancer (HNSCC) - dose escalation phase to evaluate evorpacept in combination with other drugs. This substudy is not open.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Heather McArthur
ALL
18 Years to old
PHASE2
NCT07007559
STU20251383
Inclusion Criteria:
* Histologically confirmed invasive HER2+ breast cancer.
* Received at least one prior line of therapy including T-DXd (ENHERTU) for locally advanced/metastatic HER2+ breast cancer. Prior neoadjuvant therapy which resulted in relapse within 6 months of completion of T-DXd will be considered a line of treatment for metastatic disease. Participants who discontinue T-DXd due to intolerance are considered eligible.
* Progressed on or following the most recent line of therapy.
* Eligible to receive one of the following chemotherapy options (capecitabine, eribulin, gemcitabine, paclitaxel or vinorelbine).
* Measurable disease as defined by RECIST v1.1.
* LVEF ≥50%.
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) must be 0 to 1.
* Life expectancy of at least 3 months.
* Adequate renal function (estimated creatinine clearance ≥30 mL/min as calculated using the Cockcroft-Gault equation or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
* Adequate liver function:
* Total bilirubin ≤1.5 x upper limit of normal (ULN) (≤3.0 x ULN if the participant has documented Gilbert syndrome);
* Aspartate and alanine transaminase (AST and ALT) ≤3 x ULN (≤5.0 x ULN if liver involved by metastatic disease).
* Participants must have recovered from all AEs due to previous therapies, procedures, and surgeries to baseline severity or ≤Grade 1 per NCI CTCAE v5.0 except for AEs not deemed reversible and which do not constitute a safety risk by Investigator judgment.
Exclusion Criteria:
* Participants with known CNS metastases unless treated and stable prior to enrollment.
* Prior exposure to any anti-CD47 or anti-SIRPα agent.
* Any condition that would be contraindicated to receiving trastuzumab
* Has a diagnosis of complete dihydropyrimidine dehydrogenase (DPD) deficiency or significant toxicity with prior flurouracil (5FU) based regimen
* Following anti-cancer therapy with insufficient washout before start of treatment:
• chemotherapy, hormonal therapy, radiation therapy or small molecule anti-cancer therapy within 14 days or 5 half-lives (whichever is shorter) of start of treatment.
• Immune therapy or other biologic therapy (e.g., monoclonal antibodies, antibody-drug conjugates) for the treatment of cancer for: 28 days or 5 half-lives (whichever is shorter) of start of treatment). * History of autoimmune hemolytic anemia, autoimmune thrombocytopenia, or hemolytic transfusion reaction. * Had an allogeneic tissue/solid organ transplant. * Any active, unstable cardiovascular disease. * Intolerance to or who have had a severe allergic or anaphylactic reaction to antibodies or infused therapeutic proteins or participants who have had a severe allergic or anaphylactic reaction to any of the substances included in the study drug (including excipients). * Has an active autoimmune disease that has required systemic treatment in past 2 years. * Other primary malignancy within 2 years.
DRUG: Evorpacept (ALX148), DRUG: Trastuzumab, DRUG: Paclitaxel, DRUG: Capecitabine, DRUG: Eribulin, DRUG: Gemcitabine, DRUG: Vinorelbine
Breast Cancer, Metastatic, Breast - Female, Breast - Male
metastatic, Her2+, metastatic HER2-positive breast cancer, breast cancer, HER2-positive, Evorpacept, CD47, ERBB2, Enhertu, trastuzumab deruxtecan, ASPEN-09, Herceptin, solid tumors, trastuzumab, ALX148, mBC, ASPEN-Breast
UT Southwestern
Invert-Prospective Phase II Randomized Trial of Involved Nodal Versus Elective Neck RadioTherapy
To determine the risk of solitary elective volume recurrence following involved nodal radiotherapy (INRT) versus elective nodal irradiation (ENI)
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Sher
ALL
18 Years to 99 Years old
PHASE2
NCT06477692
STU-2024-0603
Inclusion Criteria:
* Pathologically-proven diagnosis of squamous cell carcinoma of the oropharynx, larynx, or hypopharynx. Squamous cell carcinoma of unknown primary is not allowed.
* Patients must have clinically or radiographically evident measureable disease at the primary site and/or nodal stations. Diagnostic lymph node excision (≤ 2 nodes) is also allowable.
* Patients may undergo a diagnostic or therapeutic transoral resection for a T1-2 tonsil or base of tongue cancer.
* Clinical stage I-IVB (AJCC, 7th edition); stages I-II glottic cancer are excluded
* Age ≥ 18 years.
* ECOG Performance Status 0-2
* All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study treatment, 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).
* Neck CT and/or neck MRI, and PET-CT
* Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
* Distant metastasis.
* Inability to undergo either a diagnostic CT with contrast or simulation CT with contrast.
* Inability to undergo PET-CT.
* Stage I and II glottic carcinoma.
* Gross total excision of both the primary and nodal disease.
* Synchronous non-skin cancer primaries outside of the oropharynx, larynx, and hypopharynx except for low- and intermediate-risk prostate cancer and synchronous well-differentiated thyroid cancer; in the latter case, surgery may occur before or after treatment, provided all other eligibility criteria are met.
* Prior invasive malignancy with an expected disease-free interval of less than 3 years.
* Prior systemic chemotherapy for the study cancer; prior chemotherapy for a remote cancer is allowable.
* Prior radiotherapy to the region of the study cancer that would result in overlap of radiation fields.
* Subjects may not be receiving any other investigational agents.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to the chemotherapy agents in this study (if necessary).
* 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, in the opinion of the investigator, would limit compliance with study requirements.
* History of severe immunosuppression, including HIV, and organ or autologous or allogeneic stem cell transplant. DRUG: ENI using IMRT with or without chemotherapy, RADIATION: INRT, RADIATION: ENI
Head and Neck Cancer, Larynx, Lip, Oral Cavity and Pharynx
UT Southwestern; Parkland Health & Hospital System
Phase II Randomized Study of Hypofractionated Versus Conventional Radiotherapy (G-FORCE)
To compare the acute tolerance of highly conformal hypofractionated versus conventional radiotherapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Sher
ALL
18 Years and over
NA
NCT06080503
STU-2023-0715
Inclusion Criteria:
• Pathologically-proven diagnosis of squamous cell carcinoma in situ, squamous cell carcinoma, or squamous cell variants (sarcomatoid, verrucous, basaloid, and papillary subtypes) involving the glottic larynx.
• Clinical stage 0-II (AJCC, 8th edition) with direct laryngoscopy showing no evidence of greater than stage II true glottic larynx cancer and PET/CT or CT neck showing no evidence of regional disease.
• Minimum age is 18 years.
• ECOG Performance Status 0-2
• 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.
• 1 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).
• Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
• AJCC stage III or stage IV larynx cancer
• Involvement of the arytenoid cartilage beyond the vocal process.
• Prior chemotherapy for treatment of the targeted larynx lesion.
• Synchronous primaries in the head and neck
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation fields.
• Subjects smoking in excess of 1 pack of cigarettes per day.
• Subjects may not be receiving any other 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.
RADIATION: LT-SABR, RADIATION: IMRT
Laryngeal Carcinoma, Head and Neck
Larynx
UT Southwestern; Parkland Health & Hospital System
A Safety and Efficacy Study of HCB101, Fc-fusion Protein Targeting SIRPα-CD47 Pathway, in Solid or Hematological Tumors
The purpose of this study is to find out whether IV injection of HCB101 is an effective treatment for different types of advanced solid tumors or relapsed and refractory non-Hodgkin lymphoma and what side effects (unwanted effects) may occur in subjects aged 18 years old and above.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years and over
PHASE1
NCT05892718
STU-2023-1031
Inclusion Criteria:
• Able to understand and willing to sign the ICF.
• Male and female subjects of ≥18 years of age.
• Histologically/cytologically confirmed, locally advanced solid tumor: subjects with histologically or cytologically confirmed advanced solid tumors refractory to standard therapy, or for which no standard treatment exists or non-Hodgkin lymphoma, relapsed or refractory to at least 2 prior lines of therapy.
• For subjects with advanced solid tumor - must have at least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at baseline.
• For subjects with non-Hodgkin lymphoma - must have non-Hodgkin lymphoma that is measurable or assessable for response per Lugano Classification (with 2016 refinement).
• Must have ECOG performance status of 0 to 2 at Screening.
• Able to provide tumor tissue samples.
• Have life expectancy of ≥12 weeks.
Exclusion Criteria:
• With known history of hypersensitivity to any components of HCB101.
• Known active or untreated CNS metastases and/or carcinomatous meningitis.
• Have undergone a major surgery or radical radiotherapy or palliative radiotherapy or have used a radioactive drug that is not completed at least 2 weeks prior to the first dose of HCB101.
• Clinically significant cardiovascular condition.
• Any previous treatment-related toxicities which have not recovered to ≤ Grade 1 as evaluated by National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 or baseline, except alopecia and anemia.
• With known inherited or acquired bleeding disorder or bleeding diathesis. .
• Have RBC transfusion within 4 weeks prior to Screening.
• With a previously documented diagnosis of hemolytic anemia or Evans Syndrome in the last 3 months.
• Any investigational or approved systemic cancer therapy.
• Active use of vitamin K antagonist anticoagulant like warfarin. Use of low molecular weight heparin and factor Xa inhibitors will be permitted on case by case basis. There will be no restriction for daily aspirin ≤ 81 mg/QD.
• Have used herbal medication within 14 days prior to the first dose of HCB101.
• Have received any treatment targeting the CD47 or SIRPα pathway.
• Have other malignancies requiring treatment within 2 years prior to the first dose of HCB101.
• Participation in another clinical study with an investigational product administered in the last 14 days prior to receiving the first dose of HCB101.
• An investigational device used within 28 days prior to the first dose of HCB101.
• Positive for hepatitis B, active hepatitis C infections, positive for HIV, or known active or latent tuberculosis.
• Known to have a history of alcoholism or drug abuse.
DRUG: HCB101
Advanced Solid Tumor, Refractory Non-Hodgkin Lymphoma, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Hodgkins Lymphoma, Kaposis sarcoma, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Multiple Myeloma, Non-Hodgkins Lymphoma, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Stomach, Thyroid, Urinary Bladder
Immunotherapy, CD47, SIRPα, Solid Tumor, Lymphoma
UT Southwestern; Parkland Health & Hospital System
FORAGER-1: A Study of LOXO-435 (LY3866288) in Participants With Cancer With a Change in a Gene Called FGFR3 (FORAGER-1)
The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-435 by itself or when it is combined with other standard medicines that treat cancer. LOXO-435 may be used to treat cancer of the cells that line the urinary system and other solid tumor cancers that have a change in a particular gene (known as the FGFR3 gene). Participation could last up to 30 months (2.5 years) and possibly longer if the disease does not get worse.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years and over
PHASE1
NCT05614739
STU-2023-0080
Inclusion Criteria:
* Have solid tumor cancer with an FGFR3 pathway alteration on molecular testing in tumor or blood sample that is deemed as actionable
* Cohort A1: Presence of an alteration in FGFR3 or its ligands
* Cohort A2, B2, B3, and B5: Histological diagnosis of urothelial cancer (UC) that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration
* Cohorts B1 and B4: Histological diagnosis of urothelial cancer that is locally advanced or metastatic
* Cohort C1: Must have histological diagnosis of a non-urothelial solid tumor malignancy that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration
* Measurability of disease:
* Cohort A1 and B3: Measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST v1.1)
* Cohorts A2, B1, B2, B4, B5, and C1: Measurable disease required as defined by RECIST v1.1
* Have adequate tumor tissue sample available. Participants with inadequate tissue sample availability may still be considered for enrollment upon review
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 for Cohorts A1, A2, B3, and B5
* Less than or equal to 2 for Cohorts B1, B2, B4, and C1
* Prior Systemic Therapy Criteria:
* Cohort A1/C1: Participant has received all standard therapies for which the participant was deemed to be an appropriate candidate by the treating Investigator; OR the participant is refusing the remaining most appropriate standard of care treatment; OR there is no standard therapy available for the disease. There is no restriction on number of prior therapies.
* Cohort A2, B2, B3 participants must have received at least one prior regimen, and cohorts B1 and B4 participants at least 2 prior regimens, in the locally advanced or metastatic setting
* There is no restriction on number of prior therapies
* Cohort B5: Participants have not received prior systemic therapy for locally advanced or metastatic UC
* FGFR inhibitor specific requirements:
* Cohort A1/A2/B3: Prior FGFR inhibitor treatment is permitted but not required
* Cohort B1/B4: Participants must have been previously treated with erdafitinib
* Cohort B2, B5, and C1: Participants must be FGFR inhibitor naïve
Exclusion Criteria:
* Participants with primary central nervous system (CNS) malignancy
* Untreated or uncontrolled CNS metastases
* Current evidence of corneal keratopathy or retinal disorder. Individuals with asymptomatic ophthalmic conditions may be eligible
* Any serious unresolved toxicities from prior therapy
* Significant cardiovascular disease
* Prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF)
* Active uncontrolled systemic infection or other clinically significant medical conditions
* Participants who are pregnant, lactating, or plan to breastfeed during the study or within 6 months of the last dose of study treatment. Participants who have stopped breastfeeding may be enrolled DRUG: LOXO-435, DRUG: Pembrolizumab, DRUG: enfortumab vedotin
Urinary Bladder Neoplasms, Neoplasm Metastasis, Ureteral Neoplasms, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Kaposis sarcoma, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Unknown Sites, Urinary Bladder
Bladder Cancer, Bladder Urothelial Carcinoma, Urinary Bladder Cancer, Urinary Tract Cancer, Renal Pelvis Cancer, Ureter Cancer
UT Southwestern; Parkland Health & Hospital System
A Phase 2a, Single-dose, Open-label Study to Evaluate Diagnostic Performance and Safety of Pegsitacianine, an Intraoperative Fluorescence Imaging Agent for the Detection of Cancer, in Patients With Unknown Primary Head and Neck Cancer (ILLUMINATE STUDY)
This is a non-randomized, open-label, single-center, safety and imaging feasibility study of Pegsitacianine, an intraoperative fluorescence imaging agent.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Baran Sumer
ALL
18 Years to 99 Years old
PHASE2
NCT05576974
STU-2022-0460
Inclusion Criteria:
• Adults ≥18 years of age
• Biopsy-confirmed diagnosis, for primary or recurrent disease (or high clinical suspicion in the opinion of the Investigator)
• Part 1: Stage 1 to 4 HNSCC
• Part 2: UPC squamous cell carcinoma of the head and neck with metastatic disease to at least a single cervical node, AND no biopsy proven evidence of the primary cancer's location.
• Acceptable hematologic status (as standard surgery protocol requires, as determined by the Investigator), kidney function and liver function. Elevations of creatinine, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or total bilirubin \>1.5× the upper limit of normal \[ULN\] must be determined to be not clinically significant by the Investigator and approved by the Medical Monitor.
• Documented negative serum pregnancy test for women of childbearing potential (i.e., premenopausal women with intact reproductive organs and women \<2 years after menopause)
• Male patients and female patients of child-bearing potential (i.e., premenopausal women with intact reproductive organs and women \<2 years after menopause) must agree to and comply with using medically acceptable contraception including surgical sterilization (e.g., hysterectomy, bilateral oophorectomy, bilateral tubal ligation), intrauterine device, oral contraceptive, contraceptive patch, long acting injectable contraceptive, partner's vasectomy, double-barrier method (condom or diaphragm plus spermicide or condom plus diaphragm), or abstinence during the trial and for 6 months thereafter
• Agree to abstain from alcohol consumption from 72 hours before Pegsitacianine administration through completion of Study Day 10 (±48 hours) visit in Part 1 and Part 2.
• Adequate potential for follow up
Exclusion Criteria:
• Tumors at sites of which the surgeon would assess that in vivo intraoperative imaging would not be feasible.
• Life expectancy \<12 weeks
• Karnofsky Performance Status \<70%
• Hepatic impairment (Child-Pugh score \>5) or significant liver disease including active hepatitis or cirrhosis
• Lab values or any sign, symptom, or medical condition that in the opinion of the PI would prevent surgical resection
• Medical or psychiatric conditions that compromise the patient's ability to give informed consent.
• Pregnant or lactating women
• Receiving or planned to receive, during the duration of the study, concomitant medication with a high chance of hepatotoxicity, as judged by the PI based on standard protocols within the study center
• Alcohol consumption within 72 hours before Pegsitacianine administration
• Received an investigational agent within the shorter of 5 half-lives or 30 days before Pegsitacianine dosing
• Inability to adhere to the schedule of assessments or any circumstance that would interfere with the validity of assessments performed in the study
• The PI considers that the patient should not participate in the study
DRUG: Pegsitacianine
Head and Neck Cancer, Unknown Primary Cancer, Head and Neck Squamous Cell Carcinoma, Head and Neck
UT Southwestern
Evaluating the Addition of the Immunotherapy Drug Atezolizumab to Standard Chemotherapy Treatment for Advanced or Metastatic Neuroendocrine Carcinomas That Originate Outside the Lung
This phase II/III trial compares the effect of immunotherapy with atezolizumab in combination with standard chemotherapy with a platinum drug (cisplatin or carboplatin) and etoposide versus standard therapy alone for the treatment of poorly differentiated extrapulmonary (originated outside the lung) neuroendocrine cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). The other aim of this trial is to compare using atezolizumab just at the beginning of treatment versus continuing it beyond the initial treatment. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cisplatin and carboplatin are in a class of medications known as platinum-containing compounds that work by killing, stopping or slowing the growth of cancer cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair, and it may kill cancer cells. Giving atezolizumab in combination with a platinum drug (cisplatin or carboplatin) and etoposide may work better in treating patients with poorly differentiated extrapulmonary neuroendocrine cancer compared to standard therapy with a platinum drug (cisplatin or carboplatin) and etoposide alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Namrata Peswani
ALL
18 Years and over
PHASE2
NCT05058651
STU-2023-0750
Inclusion Criteria:
* Participants must have histologically-confirmed (local site pathological confirmation sufficient) extrapulmonary poorly differentiated, neuroendocrine carcinoma (NEC)
* Participants must have disease that is unresectable or metastatic and not eligible for definitive therapy as deemed per the treating investigator
* Participants must have radiologically evaluable disease, measurable or non-measurable, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. All measurable and nonmeasurable lesions must be assessed by CT scan with IV contrast of the chest/abdomen/and pelvis (or CT chest without contrast and MRI abdomen/pelvis with gadolinium contrast, if contraindication to CT iodinated contrast) within 28 days prior to registration. While may be used for routine clinical evaluation, PET scans and bone scans alone are not acceptable for disease assessment while participating in this study. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form
* Participants must have brain MRI (or CT head with contrast if there is contraindication to MRI brain) if clinically indicated within 28 days prior to registration. Note: Brain imaging is not required in participants without known and/or clinical concern for brain metastases. Participants with asymptomatic central nervous system (CNS) metastases are eligible if one or more of the following apply:
* Participants who have received treatment for brain metastases must have:
* No evidence of radiological progression (by MRI brain or CT head with contrast if there is contraindication to MRI brain) within 28 days prior to registration
* Discontinued all corticosteroids at least 14 days prior to registration
* Participants with treatment-naive brain lesions must have:
* No lesion measuring \> 2.0 cm in size in any axis
* MRI brain or CT head with contrast (if there is contraindication to MRI brain) demonstrating no evidence for mass effect, edema, or other impending neurological compromise within 28 days prior to registration
* No evidence of radiological progression (by MRI brain or CT head with contrast if there is contraindication to MRI brain) within 28 days prior to registration
* No need for \> 2 mg of dexamethasone (or equivalent of \> 10 mg prednisone) per day at time of registration
* Participants must not have symptomatic central nervous system (CNS) metastases
* Participants must not have known or suspected leptomeningeal disease
* Participants with prior history of non-metastatic (localized/locally advanced disease) extrapulmonary poorly differentiated NEC may have had prior platinum-based therapy +/- radiation +/- surgery provided that all therapy was completed \>= 6 months prior to registration
* Participants must discontinue denosumab prior to study registration and plan to replace with a bisphosphonate while on the study
* Participants must not have had prior treatment for advanced or metastatic NEC EXCEPT one cycle of platinum (carboplatin/cisplatin) + etoposide is allowed prior to registration. Other chemotherapy regimens are not allowed. For participants with prostate or urothelial NEC, prior chemotherapy for the non-NEC component (e.g. adenocarcinoma or urothelial) is allowed as long as such therapy was completed \>= 24 weeks prior to registration and participants have recovered from all prior toxicities to =\< grade 1.
* Participants must not have had prior treatment with an anti-PD-1, anti-PD-L1, antiPD-L2, CD137 agonists, anti-CTLA-4 agent, or any other immune checkpoint inhibitors for any neuroendocrine neoplasm. Immune checkpoint inhibitors given for other cancer indications are allowed provided last therapy was given at least 12 months prior to study registration
* Participants must not have received treatment with systemic immunostimulatory agents including, but not limited to, interferon and interleukin2 \[IL-2\] within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to registration
* Participants must not have had history of known severe allergy, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies, including to Chinese hamster ovary cell products or to any component of the atezolizumab formulation, cisplatin, carboplatin, or etoposide
* Participants must not be on active systemic therapy for another cancer with the exception of hormonal therapy including androgen deprivation therapy (e.g., gonadotropin-releasing hormone \[GnRH\] agonists or antagonists), which can be continued while participants are receiving protocol therapy. Use of enzalutamide or apalutamide is permitted after completion of chemotherapy and must be held during chemotherapy for participants receiving prior to enrollment. Use of darolutamide is permitted during chemotherapy. Glucocorticoid-containing regimens, including abiraterone, are not permitted.
* Participants must be \>= 18 years of age
* Participants must have a Zubrod performance status of =\< 2 within 28 days prior to registration
* Participants must have a complete medical history and physical exam within 28 days prior to registration
* Absolute neutrophil count (ANC) \>= 1.5 x 10\^9 /L (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Hemoglobin \>= 9.0 g/dl (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Platelet count \>= 100 x 10\^9/L (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x institutional upper limit of normal (ULN) (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Serum total bilirubin =\< 1.5 x ULN (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Adequate renal function as defined by any 1 of the following: 1) Measured creatinine clearance (CL) \> 50 mL/min OR 2) Calculated creatinine CL \> 50 mL/min by the Cockcroft-Gault formula OR by 24-hour urine collection for determination of creatinine clearance (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Participants must not have uncontrolled or symptomatic hypercalcemia (\> 1.5 mmol/L ionized calcium or calcium \> 12 mg/dL or corrected serum calcium \> ULN) within 14 days prior to registration. Participants who have asymptomatic hypercalcemia are eligible provided that medical therapy to treat the hypercalcemia is planned
* Participants must not have a diagnosis of immunodeficiency nor be receiving systemic steroid therapy (equivalent of \> 20 mg of hydrocortisone per day) or any other form of immunosuppressive therapy within 14 days prior to registration
* Participants must not have active or history of autoimmune disease or immune deficiency, including, but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis with the following exceptions:
* Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study
* Patients with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
* Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
* Rash must cover \< 10% of body surface area
* Disease is well controlled at baseline and requires only low-potency topical corticosteroids
* No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
* Participants must not have history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. NOTE: History of radiation pneumonitis in the radiation field (fibrosis) is permitted
* Participants must not have significant cardiovascular disease, such as New York Heart Association class II or greater cardiac disease, myocardial infarction within 3 months prior to registration, unstable arrythmias, or unstable angina
* Participants must not have had a major surgical procedure other than for diagnosis within 28 days prior to registration. Participant must not plan to receive a major surgical procedure during the course of protocol treatment. NOTE: Patient port placement is not considered a major surgery
* Participants must not have severe infections (i.e., Common Terminology Criteria for Adverse Events \[CTCAE\] grade \>= 2) at time of registration, including but not limited to hospitalization for complications for infection, bacteremia, or severe pneumonia
* Participants must not have known active tuberculosis
* Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load, with testing performed as clinically indicated
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with active HCV infection who are currently on treatment must have an undetectable HCV viral load, with testing performed as clinically indicated
* Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at time of registration and have undetectable HIV viral load within 6 months of registration
* Participants must not have prior allogeneic bone marrow transplantation or solid organ transplant
* Participants must not have received administration of a live, attenuated vaccine (e.g., FluMist \[registered trademark\]) within 28 days prior to initiation of study treatment, during treatment with atezolizumab, and not plan to receive for 5 months after the last dose of atezolizumab
* Participants must not be pregnant due to the possibility of harm to the fetus. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method (with details provided as a part of the consent process) during the treatment period and for 5 months after the final dose of atezolizumab. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a sideeffect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
* Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines BIOLOGICAL: Atezolizumab, PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Etoposide, PROCEDURE: Magnetic Resonance Imaging, OTHER: Patient Observation
Advanced Extrapulmonary Neuroendocrine Carcinoma, Metastatic Extrapulmonary Neuroendocrine Carcinoma, Recurrent Extrapulmonary Neuroendocrine Carcinoma, Unresectable Extrapulmonary Neuroendocrine Carcinoma, Anus, Bones and Joints, Brain and Nervous System, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Urinary Bladder
UT Southwestern; Parkland Health & Hospital System
Study With ABBV-CLS-484 in Participants With Locally Advanced or Metastatic Tumors
The study will assess the safety, PK, PD, and preliminary efficacy of ABBVCLS-484 as monotherapy and in combination with a PD-1 targeting agent or with a or a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). The trial aims to establish a safe, tolerable, and efficacious dose of ABBVCLS-484 as monotherapy and in combination. The study will be conducted in three parts. Part 1 Monotherapy Dose Escalation, Part 2 Combination Dose Escalation and Part 3 Dose Expansion (Monotherapy and Combination therapy). Part 1, ABBV-CLS-484 will be administered alone in escalating dose levels to eligible subjects who have advanced solid tumors. Part 2, ABBV-CLS-484 will be administered at escalating dose levels in combination with a PD-1 targeting agent or with a VEGFR TKI to eligible subjects who have advanced solid tumors. Part 3, ABBV-CLS-484 will be administered alone as a monotherapy at the determined recommended dose in subjects with locally advanced or metastatic, relapsed or refractory head and neck squamous cell carcinoma (HNSCC), relapsed or refractory non-small cell lung cancer (NSCLC), and advanced clear cell renal cell carcinoma (ccRCC). ABBV-CLS-484 will also be administered at the determined recommended dose in combination with a PD-1 targeting or with a VEGFR TKI agent in subjects with locally advanced or metastatic, HNSCC, NSCLC, MSI-H tumors refractory to PD-1/PD-L1, and advanced ccRCC.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Hans Hammers
ALL
18 Years and over
PHASE1
NCT04777994
STU-2023-0762
Inclusion Criteria:
* Must weigh at least 35 kilograms (kg).
* An Eastern Cooperative Oncology Group (ECOG) performance status \<= 2.
* Life expectancy of \>= 12 weeks.
* Laboratory values meeting protocol criteria.
* QT interval corrected for heart rate \< 470 msec (using Fridericia's correction), and no clinically significant electrocardiographic findings.
* Measurable disease defined by RECIST 1.1 criteria.
For Monotherapy and Combination Dose Escalation:
* Participants with histologically or cytologically proven metastatic or locally advanced tumors, for which no effective standard therapy exists, or where standard therapy has failed. Participants must have received at least 1 prior systemic anticancer therapy for the indication being considered.
For Monotherapy Dose Expansion only:
* Participants must have received at least 1 prior line containing PD-1/PD-L1 targeted therapy with a best response by RECIST v1.1 of CR/PR/stable (any duration) or stable disease (for greater than 6 months); AND
* Must have been previously treated with 1 or more prior lines of therapy in the locally advanced or metastatic setting with the following tumor types:
* Relapsed/refractory HNSCC
* Relapsed/refractory NSCLC
* Advanced ccRCC
For PD-1 Targeting Agent Combination Dose Expansion only:
* For the following tumor types, subject must have received at least 1 prior line containing PD-1/PD-L1 targeted therapy with response by RECIST v1.1 of CR/PR (any duration) or stable disease (for greater than 6 months):
* Relapsed HNSCC
* Relapsed NSCLC
* Relapsed Advanced ccRCC
* For the following tumor types, subject must have received at least 1 prior line containing PD-1/PD-L1 targeted therapy and have had disease progression with PD-1/PD-L1 targeted therapy:
* Locally Advanced or metastatic MSI-H tumors
For VEGFR TKI Combination Dose Expansion only:
* Relapsed advance ccRCC with no more than 1 prior VEGFR TKI
* Participants no recent history of hemorrhage, including hemoptysis, hematemesis, or melena
* Participants with poorly controlled hypertension are excluded.
Exclusion Criteria:
* Untreated brain or meningeal metastases (i.e., subjects with history of metastases are eligible provided they do not require ongoing steroid treatment and have shown clinical and radiographic stability for at least 28 days after definitive therapy)
* Unresolved Grade 2 or higher toxicities related to previous anticancer therapy except alopecia.
* Unresolved Grade 2 or higher peripheral neuropathy.
* History of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
* Recent history (within 6 months) of congestive heart failure (defined as New York Heart Association, Class 2 or higher), ischemic cardiovascular event, pericarditis, or clinically significant pericardial effusion or arrythmia.
* Recent history (within 6 months) of Childs-Pugh B or C classification of liver disease.
* History of clinically significant medical and/or psychiatric conditions or any other reason that, in the opinion of the investigator, would interfere with the subject's participation in this study or would make the subject an unsuitable candidate to receive study drug.
* History of uncontrolled, clinically significant endocrinopathy.
* Known gastrointestinal disorders making absorption of oral medications problematic; subject must be able to swallow capsules.
* If treated with a PD-1/aPD-L1 targeting or other immune-oncology agents in the past, excluded if had prior pneumonitis, prior Grade 3 or higher immune mediated toxicity, hypersensitivity to administered drug or drug related toxicity requiring discontinuation.
* Active autoimmune disease requiring systemic treatment in past 2-years (exceptions for endocrinopathies, vitiligo or atopic conditions).
* History of solid organ transplant or allogeneic stem cell transplant.
* History of other malignancy, with the following exceptions:
* No known active disease present within \>= 3 years before first dose of study treatment and felt to be at low recurrence by investigator.
* Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
* Adequately treated carcinoma in situ without evidence of disease.
* History of interstitial lung disease or pneumonitis.
* Major surgery \<= 28 days prior to first dose of study drug
* Known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection per local testing practices. DRUG: ABBV-CLS-484, DRUG: Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI), DRUG: Programmed Cell Death-1 (PD-1) Inhibitor
Advanced Solid Tumor Cancer, Cervix, Colon, Kidney, Lung/Thoracic, Ovary
Cancer, Tumor, anti-PD-1, ABBV-CLS-484, clear cell renal cell carcinoma (ccRCC), head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), relapsed or refractory (R/R), Microsatellite instability - high tumors (MSI-H), Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI)
UT Southwestern
Chemotherapy Before Surgery and Radiation Therapy or Surgery and Radiation Therapy Alone in Treating Patients With Nasal and Paranasal Sinus Cancer That Can Be Removed by Surgery
This randomized phase II trial studies how well chemotherapy before surgery and radiation therapy works compared to surgery and radiation therapy alone in treating patients with nasal and paranasal sinus cancer that can be removed by surgery. Drugs used in chemotherapy, such as docetaxel, cisplatin, and carboplatin 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 x-rays to kill tumor cells and shrink tumors. Giving chemotherapy before surgery and radiation therapy may make the tumor smaller and reduce the amount of normal tissue that needs to be removed and treated with radiation.
Call 1-888-980-6050
canceranswerline@utsouthwestern.edu
Saad Khan
ALL
18 Years and over
PHASE2
NCT03493425
STU 062018-056
Inclusion Criteria:
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* General physical condition compatible with the proposed chemotherapy and surgery
* Stage T3 or T4a, histologically-confirmed NPNSCC requiring orbital or skull base resection:
* Stages T3 and T4a disease will be included regardless of nodal status (N0 or N1-3), provided that surgical therapy would require orbital or skull base resection
* The surgical oncologist in each institution will determine the need for resection of the orbit OR base of skull at baseline for patients on both Arms A and B and following neo-adjuvant chemotherapy for patients on Arm B
* Resection of skull base will be deemed necessary according to skull base bone erosion by CT or marrow involvement by MRI is noted; for any disease abutting the skull base; or for ethmoid sinus or frontal sinus involvement
* Resection of orbital contents will be deemed necessary according to skull base society guidelines, based on involvement of periorbital fat documented by MRI imaging
* Patients must be deemed surgically resectable by the surgical teams at each institution and must have a determination of degree of anticipated structure preservation of orbit and skull base; this needs to be determined prior to randomization
* Patients may not be receiving investigational agents at time of registration, or at any time while on study and during the 4 weeks preceding enrollment
* Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to docetaxel and/or both platinum-based chemotherapy agents are excluded; patient must be able to receive at least one of the two proposed chemotherapy regimens
* Patients with evidence of distant metastases or leptomeningeal disease (LMD) are excluded
* Patients must not have received previous irradiation for head and neck tumor, skull base, or brain tumors
* 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
* Patients with a history of a different malignancy are excluded, unless the disease has not progressed for \>= 2 years
* Absolute neutrophil count (ANC) \> 1500/mm\^3 =\< 2 weeks prior to randomization
* Hemoglobin (Hgb) \> 8.0 g/dL =\< 2 weeks prior to randomization
* Platelet count \> 100,000/mm\^3 =\< 2 weeks prior to randomization
* Creatinine clearance of \> 60 ml/min; creatinine clearance may be measured or calculated; if calculating, creatinine clearance, use the Cockroft-Gault formula =\< 2 weeks prior to randomization
* Total bilirubin within normal limits (must be obtained =\< 2 weeks prior to randomization)
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) must be within the range allowing for eligibility, must be obtained \< 2 weeks prior to randomization
* Alkaline phosphatase must be within the range allowing for eligibility, must be obtained \< 2 weeks prior to randomization
* Patients with a prior history of squamous cell or basal carcinoma of the skin or in situ cervical cancer must have been curatively treated
* No current peripheral neuropathy \> grade 2 at time of randomization
* Patients must not have any co-existing condition that would preclude full compliance with the study; no prior history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
* Women must not be pregnant or breast-feeding
* All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy
* A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study
* Patients must have measurable disease; MRI and/or PET/CT scans need to be performed within 2 weeks prior to registration DRUG: Carboplatin, DRUG: Cisplatin, DRUG: Docetaxel, RADIATION: Image Guided Radiation Therapy, RADIATION: Intensity-Modulated Radiation Therapy, OTHER: Laboratory Biomarker Analysis, OTHER: Questionnaire Administration, PROCEDURE: Therapeutic Conventional Surgery
Stage III Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v6 and v7, Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7
A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements (TRIDENT-1)
Phase 1 dose escalation will determine the first cycle dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD), the biologically effective dose and recommended Phase 2 dose (RP2D) of repotrectinib given to adult subjects with advanced solid malignancies harboring an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement. Midazolam DDI substudy will examine effect of of repotrectinib on CYP3A induction. Phase 2 will determine the confirmed Overall Response Rate (ORR) as assessed by Blinded Independent Central Review (BICR) of repotrectinib in each subject population expansion cohort of advanced solid tumors that harbor a ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement. The secondary objective will include the duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and clinical benefit rate (CBR) of repotrectinib in each expansion cohort of advanced solid tumors that harbor a ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Syed Kazmi
ALL
12 Years and over
PHASE1
NCT03093116
STU-2019-1323
PHASE 1
Key
• Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor (including primary CNS tumors) (Stage IV, American Joint Committee on Cancer v.7) that harbors an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement by protocol specified tests.
• ECOG PS 0-1.
• Age ≥18 (or age ≥ 20 of age as required by local regulation).
• Capability to swallow capsules intact (without chewing, crushing, or opening).
• At least 1 measurable target lesion according to RECIST version 1.1. CNS-only measurable disease as defined by RECIST version 1.1 is allowed.
• 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.
• Patients with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol specified criteria.
• Baseline laboratory values fulfilling the following requirements:Absolute neutrophils count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L); Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine clearance Within normal limits or \> 40 mL/min; Total serum bilirubin \< 1.5 × ULN; Liver transaminases (ASTs/ALTs) \< 2.5 × ULN; \< 5 × ULN if liver metastases are present Alkaline phosphatase (ALP); \< 2.5 × ULN; \< 5 × ULN if liver and/or bone metastasis are present; Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or without supplementation
• Life expectancy ≥ 3 months. PHASE 2 Key Inclusion Criteria
• Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor (including primary CNS tumors) that harbors a ROS1, or NTRK1-3 gene fusion.
• Subject must have a documented ROS1 or NTRK1-3 gene fusion determined by tissue-based local testing using either:
• a next-generation sequencing (NGS) or quantitative polymerase chain reaction (qPCR) test will be accepted to determine molecular eligibility. • Adequate tumor tissue needs to be sent to the Sponsor designated central diagnostic laboratory for retrospective confirmation by a central diagnostic laboratory test selected by the Sponsor. OR
• a fluorescence in situ hybridization (FISH) test AND prospective confirmation of fusion status by a central diagnostic laboratory test selected by the Sponsor PRIOR to enrollment will be accepted to determine molecular eligibility. * Adequate tumor tissue must be sent to the Sponsor designated central diagnostic laboratory for prospective confirmation by a central diagnostic laboratory test selected by the Sponsor PRIOR to enrollment.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
• Age ≥12 (or age ≥ 20 as required by local regulation).
• Willing and able to provide written institutional review board (IRB)/institutional ethics committee-approved Informed Consent or an Assent signed by a parent or legal guardian for subjects age 12 to 17.
• At least 1 measurable target lesion according to RECIST (v1.1) prospectively confirmed by Blinded Independent Central Radiology Review (BICR), selected by Sponsor, PRIOR to enrollment. Subjects with CNS-only measurable disease ≥10 mm as defined by RECIST (v1.1) are eligible.
• Subjects with advanced solid tumors harboring ROS1, NTRK1, NTRK2, or NTRK3 rearrangement will be assigned into 6 distinct expansion (EXP) cohorts provided all inclusion and exclusion criteria are met. i. EXP-1: ROS1 TKI-naïve ROS1+ NSCLC ii. EXP-2: 1 Prior ROS1 TKI and 1 Platinum based chemo ROS1+ NSCLC iii. EXP-3: 2 Prior ROS1 TKIs ROS1+ NSCLC (No Chemo or IO) iv. EXP-4: 1 Prior ROS1 TKI ROS1+ NSCLC (No Chemo or IO) v. EXP-5: TRK TKI-naïve NTRK+ solid tumors vi. EXP-6: TRK TKI-pretreated NTRK+ solid tumors
• Subjects with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol specified criteria.
• Baseline laboratory values fulfilling the following requirements:Absolute neutrophils count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L); Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine clearance \> 40 mL/min; Total serum bilirubin \< 1.5 × ULN; Liver transaminases (ASTs/ALTs) \< 2.5 × ULN; \< 5 × ULN if liver metastases are present Alkaline phosphatase (ALP); \< 2.5 × ULN; \< 5 × ULN if liver and/or bone metastasis are present; Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or without supplementation
• Life expectancy ≥ 3 months. Key Exclusion Criteria PHASE 1 and PHASE 2
• Concurrent participation in another therapeutic clinical trial.
• Symptomatic brain metastases or leptomeningeal involvement.
• History of previous cancer, except for squamous cell or basal-cell carcinoma of the skin, or any in situ carcinoma that has been completely resected, requiring therapy within the previous 2 years.
• Major surgery within 4 weeks of start of repotrectinib treatment. Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study entry. Palliative radiation (≤10 fractions) must have been completed at least 48 hours prior to study entry
• Clinically significant cardiovascular disease (either active or within 6 months prior to enrollment): myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association Classification Class ≥ II), cerebrovascular accident or transient ischemic attack, symptomatic bradycardia, requirement for anti-arrhythmic medication. Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2
• 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 (QTcF) \> 470 msec obtained from 3 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, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval.
• 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.
• Peripheral neuropathy of CTCAE ≥grade 2.
• History of extensive, disseminated, bilateral, or presence of CTCAE grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis. Subjects with history of prior radiation pneumonitis are not excluded.
Inclusion Criteria:
• Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor (including primary CNS tumors) (Stage IV, American Joint Committee on Cancer v.7) that harbors an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement by protocol specified tests.
• ECOG PS 0-1.
• Age ≥18 (or age ≥ 20 of age as required by local regulation).
• Capability to swallow capsules intact (without chewing, crushing, or opening).
• At least 1 measurable target lesion according to RECIST version 1.1. CNS-only measurable disease as defined by RECIST version 1.1 is allowed.
• 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.
• Patients with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol specified criteria.
• Baseline laboratory values fulfilling the following requirements:Absolute neutrophils count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L); Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine clearance Within normal limits or \> 40 mL/min; Total serum bilirubin \< 1.5 × ULN; Liver transaminases (ASTs/ALTs) \< 2.5 × ULN; \< 5 × ULN if liver metastases are present Alkaline phosphatase (ALP); \< 2.5 × ULN; \< 5 × ULN if liver and/or bone metastasis are present; Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or without supplementation
• Life expectancy ≥ 3 months. PHASE 2 Key Inclusion Criteria
• Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor (including primary CNS tumors) that harbors a ROS1, or NTRK1-3 gene fusion.
• Subject must have a documented ROS1 or NTRK1-3 gene fusion determined by tissue-based local testing using either:
• a next-generation sequencing (NGS) or quantitative polymerase chain reaction (qPCR) test will be accepted to determine molecular eligibility. • Adequate tumor tissue needs to be sent to the Sponsor designated central diagnostic laboratory for retrospective confirmation by a central diagnostic laboratory test selected by the Sponsor. OR
• a fluorescence in situ hybridization (FISH) test AND prospective confirmation of fusion status by a central diagnostic laboratory test selected by the Sponsor PRIOR to enrollment will be accepted to determine molecular eligibility. * Adequate tumor tissue must be sent to the Sponsor designated central diagnostic laboratory for prospective confirmation by a central diagnostic laboratory test selected by the Sponsor PRIOR to enrollment.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
• Age ≥12 (or age ≥ 20 as required by local regulation).
• Willing and able to provide written institutional review board (IRB)/institutional ethics committee-approved Informed Consent or an Assent signed by a parent or legal guardian for subjects age 12 to 17.
• At least 1 measurable target lesion according to RECIST (v1.1) prospectively confirmed by Blinded Independent Central Radiology Review (BICR), selected by Sponsor, PRIOR to enrollment. Subjects with CNS-only measurable disease ≥10 mm as defined by RECIST (v1.1) are eligible.
• Subjects with advanced solid tumors harboring ROS1, NTRK1, NTRK2, or NTRK3 rearrangement will be assigned into 6 distinct expansion (EXP) cohorts provided all inclusion and exclusion criteria are met. i. EXP-1: ROS1 TKI-naïve ROS1+ NSCLC ii. EXP-2: 1 Prior ROS1 TKI and 1 Platinum based chemo ROS1+ NSCLC iii. EXP-3: 2 Prior ROS1 TKIs ROS1+ NSCLC (No Chemo or IO) iv. EXP-4: 1 Prior ROS1 TKI ROS1+ NSCLC (No Chemo or IO) v. EXP-5: TRK TKI-naïve NTRK+ solid tumors vi. EXP-6: TRK TKI-pretreated NTRK+ solid tumors
• Subjects with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol specified criteria.
• Baseline laboratory values fulfilling the following requirements:Absolute neutrophils count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L); Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine clearance \> 40 mL/min; Total serum bilirubin \< 1.5 × ULN; Liver transaminases (ASTs/ALTs) \< 2.5 × ULN; \< 5 × ULN if liver metastases are present Alkaline phosphatase (ALP); \< 2.5 × ULN; \< 5 × ULN if liver and/or bone metastasis are present; Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or without supplementation
• Life expectancy ≥ 3 months. Key Exclusion Criteria PHASE 1 and PHASE 2
• Concurrent participation in another therapeutic clinical trial.
• Symptomatic brain metastases or leptomeningeal involvement.
• History of previous cancer, except for squamous cell or basal-cell carcinoma of the skin, or any in situ carcinoma that has been completely resected, requiring therapy within the previous 2 years.
• Major surgery within 4 weeks of start of repotrectinib treatment. Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study entry. Palliative radiation (≤10 fractions) must have been completed at least 48 hours prior to study entry
• Clinically significant cardiovascular disease (either active or within 6 months prior to enrollment): myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association Classification Class ≥ II), cerebrovascular accident or transient ischemic attack, symptomatic bradycardia, requirement for anti-arrhythmic medication. Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2
• 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 (QTcF) \> 470 msec obtained from 3 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, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval.
• 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.
• Peripheral neuropathy of CTCAE ≥grade 2.
• History of extensive, disseminated, bilateral, or presence of CTCAE grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis. Subjects with history of prior radiation pneumonitis are not excluded.
DRUG: Oral repotrectinib (TPX-0005)
Locally Advanced Solid Tumors, Metastatic Solid Tumors, Colon, Liver, Lung/Thoracic, Pancreas, Rectum, Stomach
ALK, ROS1, NTRK, Sarcoma, Lung Neoplasms, Carcinoma, NSCL, NSCLC, Non Small Cell Lung, Thyroid Disease, Colonic Neoplasms, Thyroid Neoplasms, Carcinoma, Neuroendocrine, Respiratory Tract Neoplasms, Thoracic Neoplasms, Neoplasms by Site, Neoplasms, Lung Disease, Respiratory Tract Disease, Carcinoma, Bronchogenic, Bronchial Neoplasms, Endocrine System Disease, Colorectol Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Gastrointestinal Disease, Colonic Disease, Intestinal Disease, Endocrine Gland Neoplasms, Head and Neck Neoplasms, Neuroendocrine Tumors, Neuroectodermal Tumors, Neoplasms, Germ Cell and Embryonal, Neoplasms by Histologic Type, Adenocarcinoma, Non Small Cell Lung Cancer, Solid Tumors, Rearrangements, TRIDENT-1, TKI, TKI naive, TKI pretreated, Anti-tumor activity, Repotrectinib, Advanced Solid Malignancies
UT Southwestern; Parkland Health & Hospital System
Radiation Therapy With or Without Cisplatin in Treating Patients With Stage III-IVA Squamous Cell Carcinoma of the Head and Neck Who Have Undergone Surgery
This phase II trial studies how well radiation therapy with or without cisplatin works in treating patients with stage III-IVA squamous cell carcinoma of the head and neck who have undergone surgery. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. 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. It is not yet known if radiation therapy is more effective with or without cisplatin in treating patients with squamous cell carcinoma of the head and neck.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Sher
ALL
18 Years and over
PHASE2
NCT02734537
STU 072016-020
Inclusion Criteria:
* PRE-REGISTRATION (STEP 0)
* Pathologically proven diagnosis of squamous cell carcinoma (including variants such as verrucous carcinoma, spindle cell carcinoma, carcinoma not otherwise specified \[NOS\]) of the head/neck (oral cavity, oropharynx, hypopharynx or larynx); pathologic stage III or IVA (American Joint Committee on Cancer \[AJCC\] 8): T3-T4a, N0-3, M0 or T1-T2, N1-3, M0
* Patient has undergone total resection of the primary tumor with curative intent
* NOTE: Patient is to be pre-registered to screening (Step 0) and tissue submitted to Foundation Medicine as soon as possible after surgery in order to meet the 8 week deadline to register the patient to Step 1 after surgery; full assay minimum turn-around time is 17-24 days
* For oropharynx primary tumors, the patient must have negative human papillomavirus (HPV) status of the tumor as determined by p16 protein expression using immunohistochemistry (IHC)
* Patients with, per the operative and/or pathology report, positive margin(s) (tumor present at the cut or inked edge of the tumor) which is not superceded by an additional margin of tumor-negative tissue, nodal extracapsular extension, and/or gross residual disease after surgery are not eligible
* A paraffin-embedded surgical tumor tissue specimen has been located is available for shipment to Foundation Medicine, Inc. following pre-registration
* NOTE: Complete the EA3132-specific FoundationOne requisition form
* Patients with a history of a curatively treated malignancy must be disease-free for at least two years except for carcinoma in situ of cervix and/or non-melanomatous skin cancer; patients must not have received chemotherapy or investigational therapy within two years of surgical resection of the primary tumor
* Patient must not have had previous irradiation to the head and neck that would result in overlap in radiation fields for the current disease
* Patients with recurrent disease or multiple primaries are ineligible
* RANDOMIZATION (STEP 1)
* NOTE: Patient must meet all eligibility criteria outlined in pre-registration; patient may not be randomized until site has been notified that the central determination of p53 mutation status of the surgical tumor tissue has been completed and site has been notified of assay completion
* Per the operative report, the gross total resection of the primary tumor with curative intent was completed within 8 weeks prior to randomization
* The patient must have the following assessments done =\< 8 weeks prior to randomization:
* Examination by a head and neck surgeon
* Chest x-ray (or chest computed tomography \[CT\] scan or CT/positron emission tomography \[PET\] of the chest or magnetic resonance imaging \[MRI\]) to rule out distant metastatic disease
* Patient has Eastern Cooperative Oncology Group (ECOG) performance status 0-1 within 2 weeks prior to randomization
* Women must not be pregnant or breast-feeding; females of childbearing potential must have a blood or urine study within 2 weeks prior to randomization to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study and until 60 days from the last study treatment
* Absolute neutrophil count \>= 1,500/mm\^3 within 4 weeks prior to randomization
* Platelets \>= 100,000/mm\^3 within 4 weeks prior to randomization
* Total bilirubin =\< the upper limit of normal (ULN) within 4 weeks prior to randomization
* Calculated creatinine clearance must be \> 60 ml/min using the Cockcroft-Gault formula within 4 weeks prior to randomization
* Patient must not have an intercurrent illness likely to interfere with protocol therapy DRUG: Cisplatin, RADIATION: Intensity-Modulated Radiation Therapy, OTHER: Laboratory Biomarker Analysis
Head and Neck Squamous Cell Carcinoma, Hypopharyngeal Squamous Cell Carcinoma, Laryngeal Squamous Cell Carcinoma, Laryngeal Squamous Cell Carcinoma, Spindle Cell Variant, Lip and Oral Cavity Squamous Cell Carcinoma, p16INK4a Negative Oropharyngeal Squamous Cell Carcinoma, Stage III Hypopharyngeal Carcinoma AJCC v8, Stage III Laryngeal Cancer AJCC v8, Stage III Lip and Oral Cavity Cancer AJCC v8, Stage III Oral Cavity Verrucous Carcinoma, Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8, Stage IVA Hypopharyngeal Carcinoma AJCC v8, Stage IVA Laryngeal Cancer AJCC v8, Stage IVA Lip and Oral Cavity Cancer AJCC v8, Stage IVA Oral Cavity Verrucous Carcinoma, Stage IVA Oropharyngeal (p16-Negative) Carcinoma AJCC v8
Project: Every Child for Younger Patients With Cancer
This study gathers health information for the Project: Every Child for younger patients with cancer. Gathering health information over time from younger patients with cancer may help doctors find better methods of treatment and on-going care.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Laura Klesse
ALL
up to 25 Years old
N/A
NCT02402244
STU 112015-029
Inclusion Criteria:
* Enrollment must occur within 6 months of initial disease presentation OR within 6 months of refractory disease, disease progression, disease recurrence, second or secondary malignancy, or post-mortem
* Patients previously enrolled on ACCRN07 are eligible to enroll on Tracking Outcome, Registry and Future Contact components of APEC14B1 any time after they reach age of majority
* Patients with a known or suspected neoplasm that occurs in the pediatric, adolescent or young adult populations are eligible for enrollment as follows:
* All cancer cases with an International Classification of Diseases for Oncology (ICD-O) histologic behavior code of one "1" (borderline), two "2" (carcinoma in situ) or three "3" (malignant)
* All neoplastic lesions of the central nervous system regardless of behavior, i.e., benign, borderline or malignant
* All neoplastic lesions of the kidney regardless of behavior, i.e., benign, borderline or malignant
* The following other benign/borderline conditions:
* Mesoblastic nephroma
* Teratomas (mature and immature types)
* Myeloproliferative diseases including transient myeloproliferative disease
* Langerhans cell histiocytosis
* Lymphoproliferative diseases
* Desmoid tumors
* Gonadal stromal cell tumors
* Neuroendocrine tumors including pheochromocytoma
* Melanocytic tumors, except clearly benign nevi
* Ganglioneuromas
* Subjects must be =\< 25 years of age at time of original diagnosis, except for patients who are being screened specifically for eligibility onto a COG (or COG participating National Clinical Trials Network \[NCTN\]) therapeutic study, for which there is a higher upper age limit
* All patients or their parents or legally authorized representatives must sign a written informed consent and agree to participate in at least one component of the study; parents will be asked to sign a separate consent for their own biospecimen submission
* If patients or their parents or legally authorized representatives have not signed the Part A subject consent form at the time of a diagnostic bone marrow procedure, it is recommended that they initially provide consent for drawing extra bone marrow using the Consent for Collection of Additional Bone Marrow; consent using the Part A subject consent form must be provided prior to any other procedures for eligibility screening or banking under APEC14B1 OTHER: Cytology Specimen Collection Procedure, OTHER: Medical Chart Review
Adrenal Gland Pheochromocytoma, Carcinoma In Situ, Central Nervous System Neoplasm, Childhood Immature Teratoma, Childhood Kidney Neoplasm, Childhood Langerhans Cell Histiocytosis, Childhood Mature Teratoma, Congenital Mesoblastic Nephroma, Desmoid Fibromatosis, Ganglioneuroma, Lymphoproliferative Disorder, Malignant Neoplasm, Malignant Solid Neoplasm, Melanocytic Neoplasm, Myeloproliferative Neoplasm, Neoplasm of Uncertain Malignant Potential, Neuroendocrine Neoplasm, Stromal Neoplasm, Anklylosing Spondylitis, Anus, Bones and Joints, Brain and Nervous System, Breast - Female, Breast - Male, Carcinoid Tumor, Cardiovascular, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Eye and Orbit, Gall Bladder, Head and Neck, Heart, Hodgkins Lymphoma, Ill - Defined Sites, Kaposis sarcoma, Kidney, Larynx, Leukemia, Not Otherwise Specified, Leukemia, Other, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Lymphoid Leukemia, Lymphoma, Melanoma, skin, Multiple Myeloma, Mycosis Fungoides, Myeloid and Monocytic Leukemia, Non-Hodgkins Lymphoma, Nose, Other, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Sarcoma, Small Intestine, Soft Tissue, Stomach, Throat, Thyroid, Unknown Sites, Urinary Bladder, Uterine (Endometrial), Vulva
Children’s Health
Testing Docetaxel-Cetuximab or the Addition of an Immunotherapy Drug, Atezolizumab, to the Usual Chemotherapy and Radiation Therapy in High-Risk Head and Neck Cancer
This phase II/III trial studies how well radiation therapy works when given together with cisplatin, docetaxel, cetuximab, and/or atezolizumab after surgery in treating patients with high-risk stage III-IV head and neck cancer the begins in the thin, flat cells (squamous cell). Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cetuximab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The purpose of this study is to compare the usual treatment (radiation therapy with cisplatin chemotherapy) to using radiation therapy with docetaxel and cetuximab chemotherapy, and using the usual treatment plus an immunotherapy drug, atezolizumab.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Sher
ALL
18 Years and over
PHASE2
NCT01810913
STU 022013-055
Inclusion Criteria:
* PHASE II INCLUSION CRITERIA (COMPLETE AS OF 20-MAR-2020)
* Pathologically (histologically or cytologically) proven diagnosis of head and neck squamous cell carcinoma (HNSCC) involving the oral cavity (excluding lips), oropharynx (p16 negative), larynx, or hypopharynx
* Patients must have undergone gross total surgical resection of high-risk oral cavity, oropharynx (p16 negative), larynx, or hypopharynx within 63 days prior to registration; Note: patients may have biopsy under general anesthesia in an operating room followed by definitive ablative cancer surgery representing gross total resection; the gross total resection has to be done within 63 days prior to registration; if, however, patients have ablative resection but shortly recur or are determined to have persisting disease requiring re-resection to achieve gross total resection, then the patient is not eligible
* Patients must have at least 1 of the following high-risk pathologic features: extracapsular nodal extension or invasive cancer at the primary tumor resection margin (tumor on ink)
* Pathologic stage III or IV HNSCC, including no distant metastases, based upon the following minimum diagnostic workup:
* General history and physical examination by a radiation oncologist and/or medical oncologist within 84 days prior to registration;
* Examination by an ear nose throat (ENT) or head \& neck surgeon prior to surgery; a laryngopharyngoscopy (mirror and/or fiber optic and/or direct procedure), if appropriate, is recommended but not required; intra-operative examination is acceptable documentation
* Pre-operative (op) Imaging of the head and neck: A neck computed tomography (CT) (with contrast) or CT/positron emission tomography (PET) (with contrast) and/or an magnetic resonance imaging (MRI) of the neck (T1 with gadolinium and T2) within 84 days prior to surgery; Note: this imaging data (diagnostic pre-operative scan showing gross disease) is to be submitted in Digital Imaging and Communications in Medicine (DICOM) format via TRIAD; the report is to be uploaded into Rave
* Chest CT scan (with or without contrast) or CT/PET that includes the chest (with or without contrast) either within 84 days prior to surgery or within 120 days prior to registration; Note: if the CT/PET with or without contrast is done within 84 days prior to surgery, it fulfills the chest imaging requirement
* Zubrod performance status of 0-1 within 14 days prior to registration
* Age \>= 18
* Absolute granulocyte count (AGC) \>= 1,500 cells/mm\^3 (obtained within 14 days prior to registration on study)
* Platelets \>= 100,000 cells/mm\^3 (obtained within 14 days prior to registration on study)
* Hemoglobin \>= 8.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin \[Hgb\] \>= 8.0 g/dl is acceptable)
* Total bilirubin \< 2 x institutional upper limit of normal (ULN) within 14 days prior to registration
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \< 3 x institutional ULN within 14 days prior to registration
* Serum creatinine institutional ULN within 14 days prior to registration or; creatinine clearance (CC) \>= 50 ml/min within 14 days prior to registration determined by 24-hour collection or estimated by Cockcroft-Gault formula
* Negative urine or serum pregnancy test within 14 days prior to registration for women of childbearing potential
* The following assessments are required within 14 days prior to registration: sodium (Na), potassium (K), chloride (Cl), glucose, calcium (Ca), magnesium (Mg), and albumin; Note: patients with an initial magnesium \< 0.5 mmol/L (1.2 mg/dl) may receive corrective magnesium supplementation but should continue to receive either prophylactic weekly infusion of magnesium and/or oral magnesium supplementation (e.g., magnesium oxide) at the investigator's discretion
* Patients with feeding tubes are eligible for the study
* Women of childbearing potential and male participants who are sexually active must agree to use a medically effective means of birth control
* Patient must provide study specific informed consent prior to study entry, including consent for mandatory tissue submission for epidermal growth factor receptor (EGFR) analysis and for oropharyngeal cancer patients, human papilloma virus (HPV) analysis
* PHASE III: Pathologically (histologically or cytologically) proven diagnosis of head and neck squamous cell carcinoma (HNSCC) involving the oral cavity (excluding lips), oropharynx (p16 negative), larynx, or hypopharynx
* PHASE III: Patients with oropharyngeal cancer must have p16-negative based on central review prior to Step 2 registration. All patients with oropharyngeal primary must consent for mandatory tissue submission for central p16 confirmation
* PHASE III: Patients must have undergone gross total surgical resection of high-risk oral cavity, oropharynx (p16 negative), larynx, or hypopharynx within 63 days prior to registration
* Note: Patients may have biopsy under general anesthesia in an operating room followed by definitive ablative cancer surgery representing gross total resection. The gross total resection has to be done within 63 days prior to registration. If, however, patients have ablative resection but shortly recur or are determined to have persisting disease requiring re-resection to achieve gross total resection, then the patient is not eligible
* PHASE III: Patients must have at least 1 of the following high-risk pathologic features: extracapsular nodal extension or invasive cancer at the primary tumor resection margin (tumor on ink or tumor in a final separately submitted margin)
* PHASE III: Pathologic stage III or IV HNSCC (American Joint Committee on Cancer \[AJCC\] 7th edition), including no distant metastases, based upon the following minimum diagnostic workup:
* General history and physical examination by a radiation oncologist or medical oncologist within 84 days prior to registration;
* Examination by an ENT or head \& neck surgeon prior to surgery; a laryngopharyngoscopy (mirror or fiberoptic or direct procedure), if appropriate, is recommended but not required. Intra-operative examination is acceptable documentation.
* Pre-op Imaging of the head and neck: A neck CT (with contrast and of diagnostic quality) or PET/CT (with contrast and of diagnostic quality) and/or an MRI of the neck of diagnostic quality (T1 with gadolinium and T2) within 84 days prior to surgery; Note: this imaging data (diagnostic pre-operative scan showing gross disease) is to be submitted in DICOM format via TRIAD. The report is to be uploaded into Rave.
* Chest CT scan (with or without contrast) or PET/CT that includes the chest (with or without contrast) either within 84 days prior to surgery or within 120 days prior to registration; Note: If the PET/CT with or without contrast is done within 84 days prior to surgery, it fulfills the chest imaging requirement
* PHASE III: Zubrod performance status of 0-1 within 14 days prior to registration
* PHASE III: Age \>= 18
* PHASE III: Leukocytes \>= 2,500 cells/mm\^3 (obtained within 14 days prior to registration on study)
* PHASE III: Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3 (obtained within 14 days prior to registration on study)
* PHASE III: Platelets \>= 100,000 cells/mm\^3 (obtained within 14 days prior to registration on study)
* PHASE III: Hemoglobin \>= 8.0 g/dL (Note: The use of transfusion or other intervention to achieve Hgb \>= 8.0 g/dL is acceptable) (obtained within 14 days prior to registration on study)
* PHASE III: Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (however, patients with known Gilbert disease who have serum bilirubin level =\< 3 x institutional ULN may be enrolled) (within 14 days prior to registration)
* PHASE III: AST or ALT =\< 3 x institutional ULN (within 14 days prior to registration)
* PHASE III: Alkaline phosphatase =\< 2.5 x institutional ULN (within 14 days prior to registration)
* PHASE III: Creatinine clearance (CrCl) \>= 50 mL/min within 14 days prior to registration determined by 24-hour collection or estimated by Cockcroft-Gault formula
* PHASE III: Patients with feeding tubes are eligible for the study
* PHASE III: Negative urine or serum pregnancy test within 14 days prior to registration for women of childbearing potential
* PHASE III: All patients must provide study specific informed consent prior to study entry
* PHASE III: Patients positive for human immunodeficiency virus (HIV) are allowed on study, but HIV-positive patients must have:
* A stable regimen of highly active anti-retroviral therapy (HAART);
* No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections;
* A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard polymerase chain reaction (PCR)-based tests
Exclusion Criteria:
* PHASE II EXCLUSION CRITERIA (COMPLETE AS OF 20-MAR-2020)
* Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years); noninvasive cancers (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible) are permitted even if diagnosed and treated \< 3 years ago
* Patients with simultaneous primaries or bilateral tumors are excluded, with the exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0 resected differentiated thyroid carcinoma, who are eligible
* Prior systemic chemotherapy or anti-epidermal growth factor (EGF) therapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
* Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
* Severe, active co-morbidity, defined as follows:
* Unstable angina and/or congestive heart failure requiring hospitalization within 6 months prior to registration
* Transmural myocardial infarction within 6 months prior to registration
* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
* Idiopathic pulmonary fibrosis or other severe interstitial lung disease that requires oxygen therapy or is thought to require oxygen therapy within 1 year prior to registration
* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for coagulation parameters are not required for entry into this protocol
* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease and Control and Prevention (CDC) definition; note: human immunodeficiency virus (HIV) testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive; protocol-specific requirements may also exclude immuno-compromised patients.
* Grade 3-4 electrolyte abnormalities (Common Terminology Criteria for Adverse Events \[CTCAE\], version \[v.\] 4):
* Serum calcium (ionized or adjusted for albumin) \< 7 mg/dl (1.75 mmol/L) or \> 12.5 mg/dl (\> 3.1 mmol/L) despite intervention to normalize levels
* Glucose \< 40 mg/dl (\< 2.2 mmol/L) or \> 250 mg/dl (\> 14 mmol/L)
* Magnesium \< 0.9 mg/dl (\< 0.4 mmol/L) or \> 3 mg/dl (\> 1.23 mmol/L) despite intervention to normalize levels
* Potassium \< 3.0 mmol/L or \> 6 mmol/L despite intervention to normalize levels
* Sodium \< 130 mmol/L or \> 155 mmol/L despite intervention to normalize levels
* Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic
* Prior allergic reaction to cetuximab
* PHASE III: Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years) with the following exceptions: T1-2, N0, M0 resected differentiated thyroid carcinoma; Note that noninvasive cancers (For example, carcinoma in situ of the breast, oral cavity, or cervix) are permitted even if diagnosed and treated \< 3 years ago
* PHASE III: Patients with simultaneous primaries or bilateral tumors are excluded, with the exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0 resected differentiated thyroid carcinoma, who are eligible
* PHASE III: Prior systemic therapy, including cytotoxic chemotherapy, biologic/targeted therapy (such as anti-EGF therapy), or immune therapy for the study cancer; note that prior chemotherapy for a different cancer is allowable, however, a prior anti-PD-1, anti-PD-L1, or anti-PD-L2 agent is not permitted
* PHASE III: Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
* PHASE III: Severe, active co-morbidity, defined as follows:
* 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 within 6 months prior to registration
* Transmural myocardial infarction within 6 months prior to registration;
* Severe infections within 4 weeks prior to registration including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia;
* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; Note: Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible.
* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration;
* History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in a prior radiation field (fibrosis) is permitted, provided that field does not overlap with the planned radiation field for the study cancer;
* Patients with active tuberculosis (TB) are excluded;
* Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease;
* Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen \[HBsAg\] test and a positive anti-HBc \[antibody to hepatitis B core antigen\] antibody test) are eligible.
* Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
* History of allogeneic bone marrow transplantation or solid organ transplantation.
* A diagnosis of immunodeficiency:
* Acquired immune deficiency syndrome (AIDS) based upon current CDC definition; note: HIV testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
* Is receiving treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) within 2 weeks prior to registration.
* Note: Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled.
* Note: The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
* History or risk of autoimmune disease, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
* Patients with a history of autoimmune hypothyroidism who are asymptomatic and/or are on a stable dose of thyroid replacement hormone are eligible.
* Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen are eligible.
* Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
* Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
* Rash must cover less than 10% of body surface area (BSA)
* Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, flucinolone 0.01%, desonide 0.05%, aclometasone dipropionate 0.05%)
* No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation \[PUVA\], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
* PHASE III: Grade 3-4 electrolyte abnormalities (CTCAE, v. 4) within 14 days prior to registration:
* Serum calcium (ionized or adjusted for albumin) \< 7 mg/dL (1.75 mmol/L) or \> 12.5 mg/dL (\> 3.1 mmol/L) despite intervention to normalize levels;
* Glucose \< 40 mg/dL (\< 2.2 mmol/L) or \> 250 mg/dL (\> 14 mmol/L);
* Magnesium \< 0.9 mg/dL (\< 0.4 mmol/L) or \> 3 mg/dL (\> 1.23 mmol/L) despite intervention to normalize levels;
* Potassium \< 3.0 mmol/L or \> 6 mmol/L despite intervention to normalize levels;
* Sodium \< 130 mmol/L or \> 155 mmol/L despite intervention to normalize levels.
* PHASE III: Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception for up to 5 months from last study treatment; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic. Women who are breastfeeding and unwilling to discontinue are also excluded
* PHASE III: History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
* PHASE III: Patients taking bisphosphonate therapy for symptomatic hypercalcemia. Use of bisphosphonate therapy for other non-oncologic reasons (e.g., osteoporosis) is allowed
* PHASE III: Patients requiring treatment with a RANKL inhibitor (e.g. denosumab) for non-oncologic reasons who cannot discontinue it before registration
* PHASE III: Patients with known distant metastatic disease are excluded
* PHASE III: Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
* PHASE III: Major surgical procedure within 28 days prior to registration or anticipation of need for a major surgical procedure during the course of the study
* PHASE III: Administration of a live, attenuated vaccine within 4 weeks prior to registration or anticipation that such a live, attenuated vaccine will be required during the study and for patients receiving atezolizumab, up to 5 months after the last dose of atezolizumab.
* Influenza vaccination should be given during influenza season only (approximately October to DRUG: Atezolizumab, PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, BIOLOGICAL: Cetuximab, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Docetaxel, RADIATION: Intensity-Modulated Radiation Therapy, PROCEDURE: Magnetic Resonance Imaging, OTHER: Survey Administration
Oropharyngeal p16INK4a-Negative Squamous Cell Carcinoma, Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7, Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7, Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7, Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7, Stage IV Hypopharyngeal Squamous Cell Carcinoma AJCC v7, Stage IV Laryngeal Squamous Cell Carcinoma AJCC v7, Stage IV Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7, Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7
UT Southwestern; Parkland Health & Hospital System
Phase 1 Dose-escalating Study of MM-398 (Irinotecan Sucrosofate Liposome Injection) Plus Intravenous Cyclophosphamide in Recurrent or Refractory Pediatric Solid Tumors
This is a Phase 1 study of the combination of two drugs: MM-398 and Cyclophosphamide. The goal is to find the highest dose of MM-398 that can be given safely when it is used together with the chemotherapy drug Cyclophosphamide.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Patrick Leavey
All
12 Months to 20 Years old
Phase 1
NCT02013336
STU 092013-007
Inclusion Criteria:
• Histologically or cytologically-confirmed Ewing sarcoma, rhabdomyosarcoma, neuroblastoma, or osteosarcoma
• Disease progression after prior therapy in locally advanced or metastatic setting
• Measurable or evaluable disease based on the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria
• Age 12 months to <21 years
• Adequate bone marrow reserves, hepatic function, and renal function
• Recovered from effects of any prior surgery or cancer therapy
• Patients 18 years or older will provide written consent. A parent or legal guardian of a patient <18 years of age will provide informed consent and patients 11 to 18 years of age will provide written assent or as per participating institutional policy.
Exclusion Criteria:
• Clinically significant gastrointestinal disorders
• NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure
• Active infection or unexplained fever
• Known hypersensitivity to any of the components of MM-398 or other liposomal products
• Recent Investigational therapy
• Pregnant or breast feeding; females of child-bearing potential must test negative for pregnancy at the time of enrollment
Drug: MM-398 (Irinotecan Sucrosofate Liposome Injection) plus cyclophosphamide
Recurrent or Refractory Solid Tumors, Ewing Sarcoma, Rhabdomyosarcoma, Neuroblastoma, Osteosarcoma, Anus, Bones and Joints, Brain and Nervous System, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Eye and Orbit, Gall Bladder, Head and Neck, Hodgkins Lymphoma, Kaposis sarcoma, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Mycosis Fungoides, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Sarcoma, Small Intestine, Soft Tissue, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva
pediatric, MM-398, cyclophosphamide, irinotecan
Children’s Health
Abatacept in Immune Checkpoint Inhibitor Myocarditis (ATRIUM)
The primary aim is to test whether abatacept, as compared to placebo, is associated with a reduction in major adverse cardiac events (MACE) among participants hospitalized with myocarditis secondary to an immune checkpoint inhibitor (ICI). The primary outcome, MACE, is a composite of first occurrence of cardiovascular death, non-fatal sudden cardiac arrest, cardiogenic shock, significant ventricular arrythmias, significant bradyarrythmias, or incident heart failure.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Vlad Zaha
All
18 Years and over
Phase 3
NCT05335928
STU-2022-0624
Inclusion Criteria:
• Must have provided informed consent in a manner approved by the Investigator's Institutional Review Board (IRB) prior to any study-related procedure being performed. If a participant is unable to provide informed consent due to his/her medical condition, the participant's legally authorized representative may consent on behalf of the study participant, as permitted by local law and institutional Standard Operating Procedures;
• Aged greater than or equal to 18 years at the time of informed consent;
• Recent use of an FDA-approved immune checkpoint inhibitor (ICI, defined as administered an immune checkpoint inhibitor ≤ 6 months of myocarditis diagnosis), alone or in combination with other cancer therapies (i.e. chemotherapy, radiation therapy or targeted therapy). The FDA-approved ICI could be given as part of a clinical trial but not in combination with a new investigational agent which may cause myocarditis;
• A diagnosis of myocarditis.
• Hospitalized at the time of randomization;
• On 1000 mg of solumedrol per day for myocarditis or with an intent to initiate 1000 mg of solumedrol per day for myocarditis within 24 hours of first administration of study drug;
• Serum evidence of ongoing myocardial injury: Serum evidence of ongoing myocardial injury will be defined as an institutional troponin (either conventional or high-sensitivity troponin I or T, using the standard institutional assay) with a value that is ≥5 times the upper limit of the reference standard normal for that institution. The troponin assay may be adjusted based on sex depending on institutional standards. This value of troponin of ≥5 times above the institutional upper limits of normal value must be noted within 10 days prior to potential randomization. The 10-day period can be in the outpatient or inpatient setting. For example, a participant with a troponin value that on one occasion was ≥5 times the upper limits of institutional normal in the 10-day window prior to potential randomization (whether in the inpatient or outpatient setting), but later decreases below that threshold, typically due to starting corticosteroids, would still be considered eligible;
• The following laboratory parameters, not older than 48 hours at the time of randomization, and measured as part of usual care:
• Total white blood cell (WBC) count >2,500/μl
• Absolute neutrophil count (ANC) >1,500/μL
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) <20 times the upper limit of the institutional normal ranges;
• Women of childbearing potential (i.e., not postmenopausal, or surgically sterilized) must have a negative highly sensitive urine or serum pregnancy test prior to randomization. Participating women of childbearing potential must be willing to consistently use effective methods of contraception from screening until at least 90 days after administration of the last dose of study drug. Participating men must also be willing to consistently use effective methods of contraception from screening until at least 90 days after administration of the last dose of study drug; and
• Must be willing and able to abide by all study requirements and restrictions.
Exclusion Criteria:
• Must not have experienced any of the following (as defined in the section on the primary endpoint) in the 30-day period prior to randomization:
• A sudden cardiac arrest
• Cardiogenic shock as defined. A significant bradyarrhythmia (Mobitz type II second degree atrioventricular block or third degree (complete) atrio-ventricular (AV) block, for which an intervention with a temporary or permanent pacemaker is completed or recommended).
• A significant tachyarrhythmia (ventricular fibrillation of any duration or sustained ventricular tachycardia (>30 seconds, >120 beats per minute); or a ventricular tachyarrhythmia requiring intervention.
• Recent (≤2 month) exposure to abatacept or belatacept.
• Concurrent or recent (≤2 month) use of the following non-corticosteroid immunosuppressive therapies prior to randomization: mycophenolate, JAK STAT inhibitors (including but not limited to upadacitinib, tofacitinib, baricitinib, and filgotinib), tacrolimus, anti-thymocyte globulin, alemtuzumab, infliximab, and plasma exchange. The use of intravenous immunoglobulin is permitted prior to randomization and during study treatment.
• Currently enrolled in another interventional study utilizing systemic agents for the management of ICI-related toxicities.
• Female who is pregnant, breastfeeding, or is considering becoming pregnant during the study or for approximately 90 days after the last dose of study drug.
• Male who is considering fathering a child or donating sperm during the study or for approximately 30 days after the last dose of study drug.
• Any active, chronic, or recurrent viral infection that, based on the investigator's clinical assessment, makes the participant an unsuitable candidate for the study. These may include hepatitis B virus (HBV) or hepatitis C virus (HCV), recurrent or disseminated (even a single episode) herpes zoster, and disseminated (even a single episode) herpes simplex. Active HBV and HCV are defined as: HBV: hepatitis B surface antigen (HBs Ag) positive (+) or detected sensitivity on the HBV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) qualitative test for Hepatitis B core antibody (HBc Ab) positive (+) participants; HCV: HCV ribonucleic acid (RNA) detectable in any participant with anti-HCV antibody (HCV Ab). Patients with active Covid-19 infection will be excluded. This is defined as the period of ongoing symptoms in the setting of a positive Covid-19 test, or until 10 days after symptom onset and after resolution of fever for at least 24 hours, without the use of fever-reducing medications.
• Known active tuberculosis (TB), history of incompletely treated TB, suspected or known extrapulmonary TB, suspected or known systemic bacterial or fungal infections;
• Receipt of any live vaccine within four weeks prior to the first dose of study drug, or expected need of live vaccination during study participation including at least 90 days after the last dose of IV study drug.
• Any medical condition that could interfere with, or for which the treatment might interfere with, the conduct of the study or interpretation of the study results, or that would, in the opinion of the Investigator, increase the risk of the participant by participating in the study.
• Any factors that, in the Investigator's opinion, are likely to interfere with study procedures, such as history of noncompliance with scheduled appointments.
Drug: Abatacept plus, Drug: Placebo
Myocarditis Acute, Cancer, Anus, Bones and Joints, Brain and Nervous System, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Unknown Sites, Urinary Bladder
Immune checkpoint Inhibitor, Myocarditis, Abatacept, Immune therapy, Immune related adverse events
UT Southwestern