Clinical trial NCT04296370: A Study of Fluzoparib±Apatinib Versus Chemotherapy Treatment of Physician's Choice in HER2-negative Metastatic Breast Cancer Patients With Germline BRCA Mutation
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Treatment in HER2-negative Metastatic Breast Cancer Patients With Germline BRCA Mutation
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-03-05
Enrollment: 474
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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 0-1.
* 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

Primary outcomes:
measure: (Safety Lead-in) dose limited toxicity (DLT)
timeFrame: up to 21 days
measure: (Safety Lead-in) Recommended Phase II Dose (RP2D)
timeFrame: up to 21 days
measure: (Phase 3) Progression free survival(PFS) in HER2-negative Metastatic Breast Cancer patients
timeFrame: 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
Secondary outcomes:
measure: AEs+SAEs
timeFrame: from the first drug administration to within 30 days for the last treatment dose
measure: PFS by investigator's assessment
timeFrame: up to 30 months
measure: OS
timeFrame: up to 30 months
measure: Patient Reported Outcomes (PROs) assessed by EORTC QLQ C30 questionnaire
timeFrame: up to 30 months
measure: Time to progression on the next anticancer therapy (PFS2)
timeFrame: up to 30 months
measure: Objective Response Rate (ORR)
timeFrame: up to 30 months
measure: Disease control rate (DCR)
timeFrame: up to 30 months
measure: Duration of response (DoR)
timeFrame: up to 30 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Jiangsu HengRui Medicine Co., Ltd.
Study officials:
References: