MATCH Treatment Subprotocol Z1D: Nivolumab in Patients With Tumors With Mismatch Repair Deficiency
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 2
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
This phase II MATCH treatment trial identifies the effects of nivolumab in patients whose cancer has a genetic change called mismatch repair deficiency. Mismatch repair deficiency refers to cells that have mutations (changes) in certain genes that are involved in correcting mistakes made when DNA is copied in a cell. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells with mismatch repair deficiency to grow and spread. Researchers hope to learn if nivolumab will shrink this type of cancer or stop its growth.
详细描述
PRIMARY OBJECTIVE:
I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.
SECONDARY OBJECTIVES:
I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.
II. To evaluate time until death or disease progression.
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
- •Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol
- •Patients must have mismatch repair deficiency as determined via the MATCH Master Protocol
- •Women of childbearing potential (WOCBP) receiving nivolumab must agree to use adequate contraception (hormonal or double barrier method of birth control; abstinence) from one week prior to study treatment starting, during treatment, and for a period of 5 months after the last dose of nivolumab. Men receiving nivolumab and who are sexually active with WOCBP must agree to use adequate contraception (hormonal or double barrier method of birth control; abstinence) from one week prior to study treatment starting, during treatment, and for a period of 7 months after the last dose of nivolumab
- •Patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection may be eligible provided they have the following:
- •There must be no evidence of clinically significant hepatic injury from hepatitis virus infection
- •For HBV, patients must be on suppressive therapy and have undetectable HBV viral load
- •For HCV, patients must either be on suppressive therapy for HCV or have already completed therapy thought to have eradicated HCV
排除标准
- •Patients must not have known hypersensitivity to nivolumab or compounds of similar chemical or biologic composition
- •No prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40 or anti-CTLA-4 antibodies (or any other antibody targeting T cell co-regulatory pathways)
- •Patients with cancers for which nivolumab is approved or becomes approved are excluded (e.g: colorectal cancer, locally advanced or metastatic urothelial carcinoma, unresectable or metastatic melanoma, metastatic non-small cell lung cancer, advanced renal cell carcinoma, classical Hodgkin lymphoma, and recurrent or metastatic squamous cancer of the head and neck)
- •Must not have received any of the following therapies within four weeks prior to the first dose of the study drug: IL-2, interferon, or other non-study immunotherapy regimens or immunosuppressive agents
- •Must not have a history of toxic epidermal necrolysis (Stevens-Johnson syndrome)
- •Must not have received growth factors, including but not limited to granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin, etc. within 2 weeks of study drug administration. Use of such agents while on study is also prohibited. Prior use of growth factors should be documented in the patient's medical history
- •Must not have a history of any autoimmune disease: inflammatory bowel disease, (including ulcerative colitis and Crohn's disease), rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus (SLE) autoimmune vasculitis (e.g., Wegener's Granulomatosis), central nervous system (CNS) or motor neuropathy considered to be of autoimmune origin (e.g., Guillain-Barre syndrome, myasthenia gravis, multiple sclerosis). Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event). Entry of patients with autoimmune diagnoses not listed here must be approved by the protocol chair
- •Must not be on supplemental home oxygen
- •Must not have evidence of interstitial lung disease
- •Patients with a requirement for steroid treatment or other immunosuppressive treatment: Patients will be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
- •No history of severe hypersensitivity reaction to any monoclonal antibody
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: assessed at baseline, then every 8 weeks for the first 2 years, then every 12 weeks in year 3, until disease progression
Overall response rate was defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) among all eligible and treated patients. Best overall response was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. The 90% two-sided binomial exact confidence interval was calculated for ORR.
次要结局
- 6-month Progression-free Survival (PFS) Rate(assessed at baseline, then every 8 weeks for the first 2 years, then every 12 weeks in year 3, until disease progression)
- Progression-free Survival (PFS)(assessed at baseline, then every 8 weeks for the first 2 years, then every 12 weeks in year 3, until disease progression)