A Study of Fluzoparib±Apatinib Versus Chemotherapy Treatment of Physician's Choice in HER2-negative Metastatic Breast Cancer Patients With Germline BRCA Mutation
- Conditions
- Treatment in HER2-negative Metastatic Breast Cancer Patients With Germline BRCA Mutation
- Interventions
- Registration Number
- NCT04296370
- Lead Sponsor
- Jiangsu HengRui Medicine Co., Ltd.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 474
- （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 0-1.
- Adequate bone marrow, kidney and liver function.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Safety Lead-in, Doublet Arm Fluzoparib; Apatinib Fluzoparib+Apatinib Physician's choice chemotherapy Physician's choice chemotherapy Capecitabine or Vinorelbine Single Arm Fluzoparib Fluzoparib
- Primary Outcome Measures
Name Time Method (Safety Lead-in) dose limited toxicity (DLT) up to 21 days dose limited toxicity (DLT) of Fluzoparib+Apatinib in the first cycle
(Safety Lead-in) Recommended Phase II Dose (RP2D) 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 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 Outcome Measures
Name Time Method PFS by investigator's assessment up to 30 months Progression-Free-Survival
Patient Reported Outcomes (PROs) assessed by EORTC QLQ C30 questionnaire up to 30 months Comparison of the Quality of Life in study arms assessed by EORTC QLQ C30 questionnaire
Time to progression on the next anticancer therapy (PFS2) up to 30 months From date of start of next anticancer therapy to date of first documented progression of date of death from any cause, whichever comes first
AEs+SAEs from the first drug administration to within 30 days for the last treatment dose Adverse Events and Serious Adverse Events
OS up to 30 months OS is the time interval from the start of treatment to death due to any reason or lost of follow-up
Objective Response Rate (ORR) up to 30 months Number of responders Assessed by Modified Response Evaluation Criteria In Solid Tumours (RECIST v1.1) for target lesions assessed by CT or MRI
Disease control rate (DCR) up to 30 months Complete response + Partial response + Stable disease (CR+PR+SD) based on RECIST 1.1
Duration of response (DoR) up to 30 months Time from documentation of tumor response to disease progression assessed among patients who had an objective response
Trial Locations
- Locations (1)
Jiangsu HengRui Medicine Co., Ltd.
🇨🇳Shanghai, China