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
Overview
- Phase
- Phase 3
- Intervention
- Fluzoparib; Apatinib
- Conditions
- Treatment in HER2-negative Metastatic Breast Cancer Patients With Germline BRCA Mutation
- Sponsor
- Jiangsu HengRui Medicine Co., Ltd.
- Enrollment
- 474
- Locations
- 1
- Primary Endpoint
- (Safety Lead-in) dose limited toxicity (DLT)
- Status
- Recruiting
- Last Updated
- 5 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •（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.
Exclusion Criteria
- •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
Arms & Interventions
Safety Lead-in, Doublet Arm
Fluzoparib+Apatinib
Intervention: Fluzoparib; Apatinib
Single Arm
Fluzoparib
Intervention: Fluzoparib
Physician's choice chemotherapy
Capecitabine or Vinorelbine
Intervention: Physician's choice chemotherapy
Outcomes
Primary Outcomes
(Safety Lead-in) dose limited toxicity (DLT)
Time Frame: up to 21 days
dose limited toxicity (DLT) of Fluzoparib+Apatinib in the first cycle
(Safety Lead-in) Recommended Phase II Dose (RP2D)
Time Frame: 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
Time Frame: 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
Secondary Outcomes
- 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)