Phase Ib Study of Fluzoparib in Combination With Camrelizumab and Temozolomide in Advanced Melanoma With Homologous Recombination (HR) Mutation ，a Single-center Open-label Exploratory Clinical Trial
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
The purpose of this study is to evaluate how well fuzoparib in combination with camrelizumab and temozolomide works in treating patients with advanced, metastatic melanoma with the homologous recombination (HR) pathway gene mutation / alteration.
详细描述
Treatment with PARP inhibitors could represent a novel opportunity to selectively kill a subset of cancer cells with deficiencies in DNA repair pathways. Non-BRCA deficiencies in homologous recombination DNA repair genes could also enhance tumor cell sensitivity to PARP inhibitors. Therefore, PARP inhibitors are also selectively cytotoxic for cancer cells with deficiencies in DNA repair proteins other than BRCA1 and BRCA2.
In melanoma, genetic HR mutation/ alterations are rather common. Retrospective data showed that nearly18-40% of melanoma harbors a mutation in at least 1 of the HR genes in their tumor. The commonly altered genes were ARID1A, FANCA, ATM, BRCA1, ATRX and BRCA2, ATR, BRCA1 BRIP1 and SF3B1. These findings indicate that HR mutations / alterations are frequently observed in metastatic melanoma, and they suggest that PARP inhibitors could potentially be of a great clinical value in a substantial portion of the patients with advanced melanoma.
In this clinical study, clinical efficacy of fluzoparib in combination with camrelizumab and temozolomide will be evaluated by assessing an objective clinical response rate in patients with advanced, metastatic melanoma with the homologous recombination (HR) pathway gene mutation / alteration.
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
- •Histologically confirmed diagnosis of unresectable or metastatic stage III or IV melanoma;
- •Must have genetic HR and/or SF3B1 mutation/ alteration;
- •Must have measurable disease based on RECIST 1.1;
- •Must have an ECOG performance status of 0 to 1;
- •Must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline;
- •Anticipated overall survival more than 3 months;
- •Male and no pregnant female, able to adapt birth control methods during treatment.
排除标准
- •Previously treated with a PARP inhibitor;
- •Hypersensitivity to Fluzoparib or Camrelizumab or Temozolomide;
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug;
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug;
- •Patients with a history of other (including unknown primary) malignancies within 5 years prior to the first dose of trial treatment;
研究组 & 干预措施
Camre+Fluzo+TMZ
This arm will enroll patients who has advanced melanoma with a genetic HR mutation/ alteration .
干预措施: Fluzoparib Camrelizumab Temozolomide (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: 6 months
ORR of Fluzoparib in combination with Camrelizumab and Temozolomide in patients with advanced melanoma with genetic homologous recombination (HR) mutation/ alteration using RECIST v1.1
次要结局
未报告次要终点
研究者
Jun Guo
Director
Peking University Cancer Hospital & Institute