A Study of Fluzoparib±Apatinib Versus Chemotherapy Treatment of Physician's Choice in HER2-negative Metastatic Breast Cancer Patients With Germline BRCA Mutation

NCT04296370 | Unknown Phase 3

• 1 other identifier: FZPL-Ⅲ-303
• Study Type: interventional
• Target: 474
• Locations: 1 country
• Sites: 1

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.

Conditions

Treatment in HER2-negative Metastatic Breast Cancer Patients With Germline BRCA Mutation

Outcome Measures

Primary Outcomes (3)

• (Safety Lead-in) dose limited toxicity (DLT)

  dose limited toxicity (DLT) of Fluzoparib+Apatinib in the first cycle

  up to 21 days

• (Safety Lead-in) Recommended Phase II Dose (RP2D)

  Recommended Phase II Dose (RP2D) of Fluzoparib+Apatinib

  up to 21 days

• (Phase 3) Progression free survival(PFS) in HER2-negative Metastatic Breast Cancer patients

  Defined as progression free survival per RECIST 1.1 criteria according to BIRC criteria

  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 (8)

• AEs+SAEs

  from the first drug administration to within 30 days for the last treatment dose

• PFS by investigator's assessment

  up to 30 months

• OS

  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

Study Arms (3)

Safety Lead-in, Doublet Arm

EXPERIMENTAL

Fluzoparib+Apatinib

Drug: Fluzoparib; Apatinib

Single Arm

EXPERIMENTAL

Fluzoparib

Drug: Fluzoparib

Physician's choice chemotherapy

ACTIVE COMPARATOR

Capecitabine or Vinorelbine

Drug: Physician's choice chemotherapy

Interventions

Fluzoparib; Apatinib DRUG

Fluzoparib Orally twice daily; Apatinib Orally once daily

Safety Lead-in, Doublet Arm

Fluzoparib DRUG

Fluzoparib Orally twice daily

Single Arm

Physician's choice chemotherapy DRUG

Investigators will declare one of the following regimens: Capecitabine Vinorelbine

Physician's choice chemotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• （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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (1)

Jiangsu HengRui Medicine Co., Ltd.

Shanghai, China

RECRUITING

Related Publications (1)

• Li H, Liu J, Ouyang Q, Wang S, Liu Y, Teng Y, Wang X, Cheng J, Tong Z, Sun T, Yan M, Zhou X, Li F, Nie J, Shao ZM, Ye C, Wang Y, Wu X, Li Z, Wu Y, Xiong H, Li H, Gan L, Niu Z, Zhang J, Zhang Q, Pan Y, Wu X, Zhang Y, Xie W, Xiao Y, Gao J, Zhao H, Yin Y, Qian Z, Sun S, Zhang H, Wang K, Lu J, Li Y, Wang X, Yang X, Wang Y, Wang Q, Song E. Fuzuloparib with or without apatinib in patients with HER2-negative metastatic breast cancer with germline BRCA1/2 mutations (FABULOUS): interim analysis of a multicentre, three-arm, open-label, randomised, phase 3 trial. Lancet Oncol. 2025 Dec;26(12):1563-1574. doi: 10.1016/S1470-2045(25)00523-6.

  PMID: 41308673 DERIVED

MeSH Terms

Interventions

fluzoparib; apatinib

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2020
• First Posted: March 5, 2020
• Study Start: July 13, 2020
• Primary Completion: June 30, 2022
• Study Completion: June 30, 2025
• Last Updated: August 10, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)