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

Sponsor
Jiangsu HengRui Medicine Co., Ltd. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04296370
Collaborator
(none)
474
1
3
59.6
8

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Fluzoparib; Apatinib
  • Drug: Fluzoparib
  • Drug: Physician's choice chemotherapy
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
474 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jul 13, 2020
Anticipated Primary Completion Date :
Jun 30, 2022
Anticipated Study Completion Date :
Jun 30, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. (Safety Lead-in) dose limited toxicity (DLT) [up to 21 days]

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

  2. (Safety Lead-in) Recommended Phase II Dose (RP2D) [up to 21 days]

    Recommended Phase II Dose (RP2D) of Fluzoparib+Apatinib

  3. (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

  1. AEs+SAEs [from the first drug administration to within 30 days for the last treatment dose]

    Adverse Events and Serious Adverse Events

  2. PFS by investigator's assessment [up to 30 months]

    Progression-Free-Survival

  3. 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

  4. 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

  5. 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

  6. 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

  7. Disease control rate (DCR) [up to 30 months]

    Complete response + Partial response + Stable disease (CR+PR+SD) based on RECIST 1.1

  8. 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

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 70 Years
Sexes Eligible for Study:
Female
Accepts 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Jiangsu HengRui Medicine Co., Ltd. Shanghai China

Sponsors and Collaborators

  • Jiangsu HengRui Medicine Co., Ltd.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Jiangsu HengRui Medicine Co., Ltd.
ClinicalTrials.gov Identifier:
NCT04296370
Other Study ID Numbers:
  • FZPL-Ⅲ-303
First Posted:
Mar 5, 2020
Last Update Posted:
Aug 10, 2020
Last Verified:
Mar 1, 2020
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 10, 2020