Phase 2
N=164
Nivolumab With or Without Ipilimumab in Treating Patients With Metastatic Sarcoma That Cannot Be Removed by Surgery
Locally Advanced Bone Sarcoma · Locally Advanced Dedifferentiated Liposarcoma · Locally Advanced Gastrointestinal Stromal Tumor · Locally Advanced Soft Tissue Sarcoma · Metastatic Bone Sarcoma
Bottom Line
View on ClinicalTrials.gov: NCT02500797 ↗Enrolled (actual)
164
Serious AEs
47.2%
Results posted
Jun 2020
Primary outcome: Primary: Number of Participants Who Achieved a Confirmed Response — 2; 6; 1; 2 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Ipilimumab (Biological); Laboratory Biomarker Analysis (Other); Nivolumab (Biological); Quality-of-Life Assessment (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Apr 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants Who Achieved a Confirmed Response |
2; 6; 1; 2; 1; 2 | — |
| SECONDARY Number of Participants Who Experienced at Least One Grade 3 or Higher Adverse Event Regardless of Attribution |
19; 25; 11; 5; 9; 6 | — |
| SECONDARY Duration of Response |
7.4; 6.2; 14.5; 10.675; 14.6; 3.19 | — |
| SECONDARY 6-Month Clinical Benefit Rate [Initial Cohort] |
10; 12 | — |
| SECONDARY 6-Month Clinical Benefit Rate [Expansion LPS and UPS/MFH Cohorts Only] |
6.7; 35.7; 15.4; 35.7 | — |
| SECONDARY 6-Month Clinical Benefit Rate [Expansion GIST Cohort Only] |
10; 54.5 | — |
| SECONDARY Progression-free Survival (PFS) |
1.7; 4.1; 4.6; 5.5; 1.5; 2.7 | — |
| SECONDARY Overall Survival (OS) |
10.7; 14.3; 8.1; 13.1; 6.6; NA | — |
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.
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 = 350 cluster of differentiation (CD)4+ cells and no detectable viral load
- Symptomatic, untreated, or uncontrolled brain metastases present
- Active autoimmune colitis
- Autoimmune panhypopituitarism
- Autoimmune adrenal insufficiency
- Known active hepatitis B or C
- Hepatitis B can be defined as:
- Hepatitis B surface antigen (HBsAg) > 6 months
- Serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) 20,000 IU/ml (105 copies/ml), lower values 2,000-20,000 IU/ml (104-105 copies/ml) are often seen in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B
- Persistent or intermittent elevation in alanine aminotransferase (ALT)/alanine aminotransferase (AST) levels
- Liver biopsy showing chronic hepatitis with moderate or severe necroinflammation
- Hepatitis C can be defined as:
- Hepatitis C antibody (Ab) positive
- Presence of hepatitis C virus (HCV) ribonucleic acid (RNA)
- Known active pulmonary disease with hypoxia defined as:
- Oxygen saturation 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of registration
- Not pregnant and not nursing because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects; therefore for women of childbearing potential only, a negative pregnancy test done = = 1,500/mm^3
- Platelet count >= 100,000/mm^3
- Creatinine = 45 mL/min using the lean body mass formula only (Modified Cockcroft and Gault; Shargel and Yu 1985)
- Total bilirubin = 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of re-registration
- RE-REGISTRATION ELIGIBILITY CRITERIA (FOR PATIENTS WHO CROSSOVER FROM ARM 1 NIVOLUMAB ALONE TO DUAL AGENT NIVOLUMAB AND IPILIMUMAB UPON PROGRESSION): Not pregnant and not nursing because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects; therefore, for women of childbearing potential only, a negative pregnancy test done = = 1,500/mm^3
- RE-REGISTRATION ELIGIBILITY CRITERIA (FOR PATIENTS WHO CROSSOVER FROM ARM 1 NIVOLUMAB ALONE TO DUAL AGENT NIVOLUMAB AND IPILIMUMAB UPON PROGRESSION): Platelet count >= 100,000/mm^3
- RE-REGISTRATION ELIGIBILITY CRITERIA (FOR PATIENTS WHO CROSSOVER FROM ARM 1 NIVOLUMAB ALONE TO DUAL AGENT NIVOLUMAB AND IPILIMUMAB UPON PROGRESSION): Creatinine = 45 mL/min (using lean body mass formula only [Modified Cockcroft and Gault; Shargel and Yu 1985])
- RE-REGISTRATION ELIGIBILITY CRITERIA (FOR PATIENTS WHO CROSSOVER FROM ARM 1 NIVOLUMAB ALONE TO DUAL AGENT NIVOLUMAB AND IPILIMUMAB UPON PROGRESSION): Total bilirubin =< 1.5 x ULN in absence of Gilbert disease (total bilirubin =< 3 x ULN with Gilbert); if hyperbilirubinemia is clearly attributed to liver metastases, total bilirubin =< 3 x ULN is permitted
- RE-REGISTRATION ELIGIBILITY CRITERIA (FO
Data sourced from ClinicalTrials.gov (NCT02500797). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.