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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Treatment in HER2-negative Metastatic Breast Cancer Patients With Germline BRCA Mutation
• Intervention / Treatment: Drug: Fluzoparib; Drug: Fluzoparib; Apatinib; Drug: Physician's choice chemotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 474
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Jiangsu HengRui Medicine Co., Ltd.
    • Contact: Quanren Wang; Phone Number: +86 18036618570; Email: wangquanren@hrglobe.cn
    • Contact: Xiaodi Wang; Phone Number: +86 13811442099; Email: wangxiaodi@hrglobe.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Safety Lead-in, Doublet Arm; Fluzoparib+Apatinib	Drug: Fluzoparib; Apatinib; Fluzoparib Orally twice daily; Apatinib Orally once daily
Experimental: Single Arm; Fluzoparib	Drug: Fluzoparib; Fluzoparib Orally twice daily
Active Comparator: Physician's choice chemotherapy; Capecitabine or Vinorelbine	Drug: Physician's choice chemotherapy; Investigators will declare one of the following regimens: Capecitabine Vinorelbine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
(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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
AEs+SAEs	Adverse Events and Serious Adverse Events	from the first drug administration to within 30 days for the last treatment dose
PFS by investigator's assessment	Progression-Free-Survival	up to 30 months
OS	OS is the time interval from the start of treatment to death due to any reason or lost of follow-up	up to 30 months
Patient Reported Outcomes (PROs) assessed by EORTC QLQ C30 questionnaire	Comparison of the Quality of Life in study arms assessed by EORTC QLQ C30 questionnaire	up to 30 months
Time to progression on the next anticancer therapy (PFS2)	From date of start of next anticancer therapy to date of first documented progression of date of death from any cause, whichever comes first	up to 30 months
Objective Response Rate (ORR)	Number of responders Assessed by Modified Response Evaluation Criteria In Solid Tumours (RECIST v1.1) for target lesions assessed by CT or MRI	up to 30 months
Disease control rate (DCR)	Complete response + Partial response + Stable disease (CR+PR+SD) based on RECIST 1.1	up to 30 months
Duration of response (DoR)	Time from documentation of tumor response to disease progression assessed among patients who had an objective response	up to 30 months

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2020
• Primary Completion (Anticipated): June 30, 2022
• Study Completion (Anticipated): June 30, 2025

Study Registration Dates

• First Submitted: March 3, 2020
• First Submitted That Met QC Criteria: March 3, 2020
• First Posted (Actual): March 5, 2020

Study Record Updates

• Last Update Posted (Actual): August 10, 2020
• Last Update Submitted That Met QC Criteria: August 6, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: FZPL-Ⅲ-303

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No