Phase 2 Study of Ipilimumab Plus Nivolumab in Combination With Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma
Overview
- Phase
- Phase 2
- Intervention
- Ipilimumab
- Conditions
- Soft Tissue Sarcoma
- Sponsor
- Kristen Ganjoo
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Clinical Response
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
The purpose of this Phase 2 study is to
- find out if the study drugs (ipilimumab plus nivolumab) in combination with cryotherapy will help participants with metastatic or locally advanced soft tissue sarcoma;.
- find out how safe are ipilimumab plus nivolumab given in combination with cryotherapy, and what side effects may be related to treatment.
- find out how do the study drugs in combination with cryotherapy work in soft tissue sarcoma.
Detailed Description
Primary Objectives: 1) Assess whether the rate of clinical benefit is sufficiently high to merit promise for further study Secondary Objectives: 1. Characterize the 6-month progression-free survival rate 2. Assess whether the treatment yields a reasonably safe and tolerable profile
Investigators
Kristen Ganjoo
Associate Professor of Medicine
Stanford University
Eligibility Criteria
Inclusion Criteria
- •Unresectable or metastatic soft tissue sarcoma
- •≥ 1 prior systemic therapy for sarcoma, including adjuvant systemic therapy
- •Age ≥ 18 years
- •4 Life expectancy \> 3 months
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Lab values as below:
- •Absolute neutrophil count (ANC) ≥ 1,000/mm\^3 Platelet count ≥ 75,000/mm\^3; Creatinine ≤ 1.5 x upper limit of normal (ULN) OR calculated (calc.); creatinine clearance \> 45 mL/min using the lean body mass formula only; Total bilirubin ≤ 1.5 x ULN in absence of Gilbert disease (total bilirubin ≤ 3 x ULN with Gilbert); also, if hyperbilirubinemia is clearly attributed to liver metastases total bilirubin ≤ 3 x ULN is permitted AST/ALT ≤ 3 x ULN;Thyroid stimulating hormone (TSH) within normal limits (WNL);supplementation is acceptable to achieve a TSH WNL; in subjects with abnormal TSH if free T4 is normal and subject is clinically euthyroid, subject is eligible
- •Any toxic effects of prior therapy (except alopecia) must be resolved to NCI CTCAE, version 5.0, Grade 1 or less
- •Ability to understand and the willingness to sign a written informed consent
- •Women of childbearing potential (WOCBP) receiving nivolumab must be willing to adhere to contraception for a period of 5 months after the last dose of nivolumab. Men receiving nivolumab and who are sexually active with WOCBP will be instructed and must be willing to adhere to contraception for a period of 7 months after the last dose of nivolumab.
Exclusion Criteria
- •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)
- •History of the following:
- •Active known or suspected autoimmune disease
- •Known human immunodeficiency virus (HIV) (Subjects with lymphocytes \> 350 cluster of differentiation (CD)4+ cells and no detectable viral load are eligible)
- •Hepatitis B
- •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 to 20,000 IU/mL (104 to 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 Hepatitis C antibody (Ab) positive Presence of hepatitis C virus (HCV) ribonucleic acid (RNA) 3.2.2.5 Known active pulmonary disease with hypoxia defined as: Oxygen saturation \< 85% on room air or Oxygen saturation \< 88% despite supplemental oxygen
- •Systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 7 days of registration
- •Received any live/attenuated vaccine (eg, varicella, zoster, yellow fever, rotavirus, oral polio and measles, mumps, rubella (MMRI) within 30 days before initiation of treatment on this protocol.
Arms & Interventions
Ipilimumab/nivolumab + cryotherapy
1 mg/kg with nivolumab 3 mg/kg every 3 weeks x 4 doses. (One cycle of treatment is 3 weeks). Cryotherapy (cryoablation) will be performed between investigational agent treatment Cycles 1 and 2
Intervention: Ipilimumab
Ipilimumab/nivolumab + cryotherapy
1 mg/kg with nivolumab 3 mg/kg every 3 weeks x 4 doses. (One cycle of treatment is 3 weeks). Cryotherapy (cryoablation) will be performed between investigational agent treatment Cycles 1 and 2
Intervention: Cryoablation
Ipilimumab/nivolumab + cryotherapy
1 mg/kg with nivolumab 3 mg/kg every 3 weeks x 4 doses. (One cycle of treatment is 3 weeks). Cryotherapy (cryoablation) will be performed between investigational agent treatment Cycles 1 and 2
Intervention: Nivolumab
Outcomes
Primary Outcomes
Clinical Response
Time Frame: 14 weeks
Clinical benefit was assessed on the basis of clinical response per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria: * Complete response (CR) = Disappearance of all target lesions; all lymph nodes \< 10 mm on the short axis; no new lesions. * Partial response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions; no new lesions. * Stable disease (SD) = Small changes that do not meet any of the above criteria; no new lesions. * Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s). Clinical benefit was defined as CR + PR. The primary outcome is expressed as the total number of participants who receive clinical benefit within 14 weeks, a number without dispersion. Rates of all clinical responses are reported.
Secondary Outcomes
- Related Adverse Events (Toxicity)(24 months)
- Immune-related Clinical Response (irRECIST) Rate(16 weeks)
- Progression-free Survival (PFS)(6 months)