Randomized Phase II Study of Nivolumab With or Without Ipilimumab in Patients With Metastatic or Unresectable Sarcoma
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Locally Advanced Bone Sarcoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 164
- Locations
- 648
- Primary Endpoint
- Number of Participants Who Achieved a Confirmed Response
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This randomized phase II trial studies how well nivolumab with or without ipilimumab works in treating patients with sarcoma that has spread from the primary site to other parts of the body (metastatic) or cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether nivolumab works better with or without ipilimumab in treating patients with metastatic or unresectable sarcoma.
Detailed Description
PRIMARY OBJECTIVE: I. To evaluate the confirmed response rate of single agent nivolumab and dual agent nivolumab plus ipilimumab in patients with locally advanced/unresectable or metastatic soft tissue sarcoma. SECONDARY OBJECTIVES: I. To evaluate adverse event rates (National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]4.0) within each treatment arm. II. To evaluate duration of response, clinical benefit rate, time to progression, progression-free survival, and overall survival within each treatment arm. CORRELATIVE SCIENCE OBJECTIVES: I. To potentially detect an early signal of confirmed response rate within a histologically defined patient cohort. II. To assess the potential association between programmed cell death 1 ligand 1 (PD-L1) expression (by immunohistochemistry \[IHC\]) and clinical outcome, within each treatment. III. To evaluate associations between selected biomarker measured in serial peripheral blood and with clinical efficacy, within each treatment. IV. To evaluate the association between selected biomarker measured in tumor tissue with clinical efficacy, within each treatment. V. To evaluate the association between baseline tumor mutational burden and neoantigen production with clinical efficacy within each treatment. EXPLORATORY PHASE II OBJECTIVES (CROSSOVER TREATMENT): I. To evaluate secondary endpoints within patients crossing over to dual agent nivolumab plus ipilimumab after experiencing progressive disease while receiving single agent nivolumab. II. To evaluate correlative science objectives endpoints within patients crossing over to dual agent nivolumab plus ipilimumab after experiencing progressive disease while receiving single agent nivolumab. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive nivolumab intravenously (IV) over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress after 10 weeks on single agent nivolumab may elect to cross over to Arm II. ARM II: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator. After completion of study treatment, patients are followed up at 4 weeks and then every 6 months 3 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •PRE-REGISTRATION ELIGIBILITY CRITERIA:
- •Patients must have a formalin-fixed, paraffin-embedded (FFPE) tumor block OR 1 representative hematoxylin and eosin (H\&E) and 20 unstained sarcoma tissue slides available for submission to central pathology review; this review is mandatory prior to registration to confirm eligibility
- •REGISTRATION ELIGIBILITY CRITERIA:
- •Patients must have histologically confirmed bone or soft tissue sarcoma by central pathology review
- •Patients must have histologically confirmed liposarcoma (LPS) (only dedifferentiated and pleomorphic; well differentiated not eligible), undifferentiated pleomorphic sarcoma (UPS)/malignant fibrous histiocytoma (MFH), or gastrointestinal stromal tumor (GIST)
- •Measurable disease
- •Locally advanced/unresectable or metastatic disease
- •\>= 1 prior systemic therapy for sarcoma, including adjuvant systemic therapy
- •No prior therapy with ipilimumab or nivolumab, or any agent targeting programmed cell death 1 (PD-1), PD-L1 or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)
- •No treatment with biologic therapy, immunotherapy, chemotherapy, investigational agent for malignancy, or radiation =\< 28 days before study registration; no treatment with nitrosourea or mitomycin =\< 42 days before study registration; for GIST, tyrosine kinase inhibitor can be continued for up to 3 days prior to initiation of study treatment
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Number of Participants Who Achieved a Confirmed Response
Time Frame: Up to 44 months
The number of participants who achieved a confirmed response is defined as the number of patients having a best objective tumor status of complete response (CR) or partial response (PR) lasting at least 4 weeks as determined using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. (CR: Disappearance of all evidence of disease, PR: Regression of measurable disease and no new sites).
Secondary Outcomes
- Number of Participants Who Experienced at Least One Grade 3 or Higher Adverse Event Regardless of Attribution(Up to 4 weeks after completion of study treatment)
- Duration of Response(Time from first response to progression, assessed up to 3 years)
- Progression-free Survival (PFS)(Time from randomization to first of either disease progression or death from any cause, assessed up to 3 years)
- 6-Month Clinical Benefit Rate [Initial Cohort](At 6 months)
- Overall Survival (OS)(Time from randomization to death from any cause, assessed up to 3 years)
- 6-Month Clinical Benefit Rate [Expansion LPS and UPS/MFH Cohorts Only](At 6 months)
- 6-Month Clinical Benefit Rate [Expansion GIST Cohort Only](At 6 months)