Treatment in HER2-negative Metastatic Breast Cancer Patients With Germline BRCA Mutation
Conditions
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.
Interventions
Fluzoparib Orally twice daily; Apatinib Orally once daily
DRUGFluzoparib
Fluzoparib Orally twice daily
Investigators will declare one of the following regimens: Capecitabine Vinorelbine
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
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 0-1. * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| (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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| PFS by investigator's assessment | up to 30 months | Progression-Free-Survival |
| 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 |
Countries
China
Outcome results
None listed