A Phase II, Signal-Seeking Trial of the Clinical Benefit Rate Associated With Pamiparib in Subjects With Germline or Somatic BRCA1/2 High Grade Serous Ovarian Cancer or Carcinosarcoma Who Have Progressed on P-gp Substrate Chemotherapy or PARPi With the Presence of an ABCB1 Fusion and the Absence of a BRCA1/2 Reversion
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Clinical benefit rate
研究概览
简要总结
This study is a phase II, multi-centre, open label study in patients with advanced ovarian cancer. The treatment being tested is Pamiparib, with daily dosing.
All patients enrolled to the study will receive treatment with pamiparib. Patients will be selected for entry into the study based on the molecular signature of their cancer.
详细描述
Ovarian cancer is the deadliest gynaecologic cancer in Western women. Although initially responsive to therapy, drug resistance commonly evolves.
Novel mechanisms of drug resistance in ovarian cancer have been identified and include genetic mutations that result in the activation of a drug efflux pump and secondary mutations in BRCA1/2 genes that restore the cancer cell's ability to repair treatment related DNA damage. It is hypothesized that patients with BRCA1/2 mutant high grade serous ovarian cancer or carcinosarcoma who have progressed on recent therapy and have an activated efflux pump without a secondary BRCA1/1 mutation will be selectively sensitive to a new PARPi, Pamiparib, which does not get effluxed out of cancer cells.
The primary objective of this trial is to assess the clinical benefit rate at > 4 months in 2 cohorts of patients (cohort 1: post substrate-PARP inhibitor and cohort 2: post chemotherapy) defined as response or absence of progression. Secondary objectives are to determine the median progression free and overall survival of patients treated with Pamiparib and the impact on symptom burden and benefit.
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
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Pamiparib (BGB-290)
Drug: Pamiparib Oral capsules 60mg twice daily continuously Although treatment is continuous, a cycle is defined as 4 weeks or 28 days.
干预措施: Pamiparib (Drug)
结局指标
主要结局
Clinical benefit rate
时间窗: Assessed at 16 weeks after commencing treatment.
as assessed by RECIST v1.1 or by Gynaecological Cancer Intergroup (GCIG) Cancer antigen (CA)-125 criteria
次要结局
- Best overall response according to RECIST v1.1(Assessed for up to 3 years after the last patient enrolled has commenced treatment.)
- Best overall response according to CA-125(Assessed for up to 3 years after the last patient enrolled has commenced treatment.)
- Patient reported symptom burden(At the time of consent to screening, at every cycle to 16 weeks, then every 4 cycles, and again at the time of progression. Assessed for up to 3 years after the last patient enrolled has commenced treatment.)
- Frequency of ABCB1 fusions and BRCA1/2 reversions(At Baseline)
- Median progression free survival(Through study completion, on average 6 months.)
- Median overall survival(Assessed for up to 3 years after the last patient enrolled has commenced treatment.)
- Duration of response(Assessed for up to 3 years after the last patient enrolled has commenced treatment.)
- Patient reported results of the 40 item State-trait anxiety inventory for adults (STAI-ADTM)(This will be assessed 3 times - at the time of pre-screening consent, immediately prior to clinician consult with notification of pre-screening results, and immediately following notification of pre-screening results.)
- The type, grade and relationship to treatment of adverse events(During the treatment period, on average 3 years)