A Randomized Phase 2 Study of Nivolumab Monotherapy Versus Nivolumab Combined With Ipilimumab in Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumor (GIST)
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Gastrointestinal Stromal Tumor
- Sponsor
- Jonsson Comprehensive Cancer Center
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- Overall response rate defined as the number of subjects with a best objective response of confirmed CR or PR divided by the number of subjects
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This randomized phase II trial studies how well nivolumab with or without ipilimumab works in treating patients with gastrointestinal stromal tumor that has spread to other places in the body or cannot be removed by surgery. Monoclonal antibodies, such as nivolumab and ipilimumab, interfere with the ability of tumor cells to grow and spread.
Detailed Description
PRIMARY OBJECTIVES: I. To assess the response rate of nivolumab alone and in combination with ipilimumab in subjects with metastatic or locally advanced/unresectable gastrointestinal stromal tumor (GIST). SECONDARY OBJECTIVES: I. Ascertain the response rate of nivolumab alone and in combination of ipilimumab in subjects with metastatic or locally advanced/unresectable GIST by Choi criteria. II. Assess the progression-free survival (PFS). III. Ascertain the clinical benefit rate (CBR = complete response \[CR\] + partial response \[PR\] and stable disease \[SD\]) of nivolumab and ipilimumab in refractory/unresectable GIST. IV. Explore the safety of nivolumab monotherapy and nivolumab and ipilimumab in this population assessed by the frequency and severity of adverse events (AEs). TERTIARY OBJECTIVES: I. Compare RR and CBR in patients whose tumors are programmed cell death ligand 1 (PD-L1) positive (+) and PD-L1 negative (-) at baseline. II. In the patients who are PD-L1 positive, compare RR and CBR in patients with 1% and 5% tumor membrane staining. III. Determine the baseline mutational load of patients at the start of treatment. IV. Determine the response to treatment based on the baseline mutation load and baseline GIST mutations. V. Determine the response rate based on GIST mutational status. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive nivolumab intravenously (IV) over 60 minutes on day 1. Courses repeat every 14 days for up to 2 years in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive nivolumab IV over 30 minutes on day 1 and ipilimumab IV over 30 minutes every 6 weeks. Courses repeat every 14 days for up to 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written informed consent must be obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
- •Life expectancy \> 12 weeks
- •Histological confirmation of GIST
- •Mutational testing of patient samples for KIT and platelet-derived growth factor receptor (PDGFR) mutations; (this will not hold up starting therapy, but will be done for all patients lacking up front mutational testing)
- •Patients must have refused or have evidence of intolerance to or progression on imatinib
- •This study permits the re-enrollment of a subject that has discontinued the study as a pre-treatment failure (i.e., subject has not been randomized / has not been treated); if re-enrolled, the subject must be re-consented
- •Adequate archival tissue must be available from the prior 3 months to signing consent; if not, an adequate tumor specimen obtained by either excisional biopsy, incisional biopsy or core needle biopsy must be sent to the central pathology lab for evaluation; the material must measure at least 0.8 × 0.1 cm in size or contain at least 100 tumor cells
- •Measurable tumor lesions according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
- •Hemoglobin \>= 9 g/dL
Exclusion Criteria
- •Palliative surgery and/or radiation treatment within 28 days prior to course 1 day 1 (C1D1)
- •Localized therapy of non-target lesions is allowed
- •No steroids are permitted within 28 days of C1D1; or doses \< 10mg/day prednisone equivalent or levels necessary for physiologic replacement
- •Women who are of pregnant or breastfeeding
- •Inability to give informed consent
- •An inadequate tumor specimen as defined by the local pathologist
- •History of other malignancies except cured basal cell carcinoma, cutaneous squamous cell carcinoma, melanoma in situ, superficial bladder cancer or carcinoma in situ of the cervix; for other malignancies, must be documented to be free of cancer for \>= 2 years; all other cases can be considered on a case by case basis at the discretion of the principal investigator
- •Any condition that might interfere with the subject's participation in the study, safety, or in the evaluation of the study results
- •Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study
- •Prior exposure to any anti-PD-1 or anti-PD-L1 antibody, or any anti-cytotoxic T-lymphocyte-associated protein (CTLA) 4 antibodies
Outcomes
Primary Outcomes
Overall response rate defined as the number of subjects with a best objective response of confirmed CR or PR divided by the number of subjects
Time Frame: Up to 2 years
Will utilize an exact binomial test to compare the RECIST response rate separately within each of the two study arms. Additionally, an exact 95% confidence interval will be constructed within each arm.
Secondary Outcomes
- Frequency and severity of AEs assessed by NCI CTCAE v 4.03(Up to 2 years)
- Progression free survival time(Up to 2 years)
- Clinical benefit rate(Up to 2 years)
- Response rate by Choi criteria(Up to 2 years)