Phase 2 Study of Ipilimumab Plus Nivolumab in Combination With Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Clinical Response
研究概览
简要总结
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.
详细描述
Primary Objectives:
- Assess whether the rate of clinical benefit is sufficiently high to merit promise for further study
Secondary Objectives:
- Characterize the 6-month progression-free survival rate
- Assess whether the treatment yields a reasonably safe and tolerable profile
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
- •If female, pregnant or lactating. (Women of childbearing potential are required to have a negative pregnancy test within 24 hours prior to the initial administration of study drug)
研究组 & 干预措施
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
干预措施: Ipilimumab (Drug)
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
干预措施: Cryoablation (Procedure)
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
干预措施: Nivolumab (Drug)
结局指标
主要结局
Clinical Response
时间窗: 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.
次要结局
- Related Adverse Events (Toxicity)(24 months)
- Immune-related Clinical Response (irRECIST) Rate(16 weeks)
- Progression-free Survival (PFS)(6 months)
研究者
Kristen Ganjoo
Associate Professor of Medicine
Stanford University