A Phase III, Open Label, Randomised, Controlled, Multi-centre Study to Assess the Efficacy and Safety of Fluzoparib±Apatinib Versus Physicians Choice Chemotherapy in the Treatment of HER2-negative Metastatic Breast Cancer Patients With Germline BRCA1/2 Mutations
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 474
- 试验地点
- 1
- 主要终点
- (Safety Lead-in) dose limited toxicity (DLT)
研究概览
简要总结
This is a multicenter, randomized, open-label, 3-arm Phase 3 study to evaluate the efficacy and safety of Fluzoparib alone or with Apatinib versus Physicians Choice Chemotherapy, as treatment, in patients with a Germline BRCA Mutation and HER2-negative Metastatic Breast Cancer. The study contains a Safety Lead-in Phase in which the safety and tolerability of Fluzoparib+Apatinib will be assessed prior to the Phase 3 portion of the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •（Saftey Lead-in + phase 3）Germline mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious
- •（Saftey Lead-in + phase 3）human epidermal growth factor receptor type 2 (HER2)-negative metastatic breast cancer
- •（Saftey Lead-in + phase 3）had received ≤2 lines of chemotherapy for mBC
- •（Saftey Lead-in + phase 3）Prior therapy with an anthracycline and a taxane in either an adjuvant or metastatic setting.
- •ER/PR breast cancer positive patients must have received and progressed on at least one endocrine therapy (adjuvant or metastatic), or have disease that the treating physician believes to be inappropriate for endocrine therapy.
- •ECOG performance status 0-
- •Adequate bone marrow, kidney and liver function.
排除标准
- •Prior treatment with a poly (ADP-ribose) polymerase (PARP) inhibitor or Apatinib
- •Prior malignancy unless curatively treated and disease-free for > 5 years prior to study entry. Prior adequately treated non-melanoma skin cancer, in situ cancer of the cervix, DCIS or stage I grade 1 endometrial cancer allowed
- •Radiation or anti-hormonal therapy or other targeted anticancer therapy within 14 days before randomization
- •Known to be human immunodeficiency virus positive
- •Known active hepatitis C virus, or known active hepatitis B virus
- •Untreated and/or uncontrolled brain metastases
- •Pregnant or breast-feeding women
研究组 & 干预措施
Safety Lead-in, Doublet Arm
Fluzoparib+Apatinib
干预措施: Fluzoparib; Apatinib (Drug)
Single Arm
Fluzoparib
干预措施: Fluzoparib (Drug)
Physician's choice chemotherapy
Capecitabine or Vinorelbine
干预措施: Physician's choice chemotherapy (Drug)
结局指标
主要结局
(Safety Lead-in) dose limited toxicity (DLT)
时间窗: up to 21 days
dose limited toxicity (DLT) of Fluzoparib+Apatinib in the first cycle
(Safety Lead-in) Recommended Phase II Dose (RP2D)
时间窗: up to 21 days
Recommended Phase II Dose (RP2D) of Fluzoparib+Apatinib
(Phase 3) Progression free survival(PFS) in HER2-negative Metastatic Breast Cancer patients
时间窗: Radiological scans performed at baseline then every ~6 weeks up to 30 weeks, then every ~ 9 weeks thereafter until objective radiological disease progression. Assessed up to a maximum of 30 months
Defined as progression free survival per RECIST 1.1 criteria according to BIRC criteria
次要结局
- PFS by investigator's assessment(up to 30 months)
- Patient Reported Outcomes (PROs) assessed by EORTC QLQ C30 questionnaire(up to 30 months)
- Time to progression on the next anticancer therapy (PFS2)(up to 30 months)
- AEs+SAEs(from the first drug administration to within 30 days for the last treatment dose)
- OS(up to 30 months)
- Objective Response Rate (ORR)(up to 30 months)
- Disease control rate (DCR)(up to 30 months)
- Duration of response (DoR)(up to 30 months)