Back to resultsA Study of Fluzoparib±Apatinib Versus Chemotherapy Treatment of Physician's Choice in HER2-negative Metastatic Breast Cancer Patients With Germline BRCA Mutation
Primary Purpose
Treatment in HER2-negative Metastatic Breast Cancer Patients With Germline BRCA Mutation
Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Fluzoparib; Apatinib
Fluzoparib
Physician's choice chemotherapy
Sponsored by
About this trial
This is an interventional treatment trial for Treatment in HER2-negative Metastatic Breast Cancer Patients With Germline BRCA Mutation
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
Sites / Locations
- Jiangsu HengRui Medicine Co., Ltd.Recruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
Safety Lead-in, Doublet Arm
Single Arm
Physician's choice chemotherapy
Arm Description
Fluzoparib+Apatinib
Fluzoparib
Capecitabine or Vinorelbine
Outcomes
Primary Outcome Measures
(Safety Lead-in) dose limited toxicity (DLT)
dose limited toxicity (DLT) of Fluzoparib+Apatinib in the first cycle
(Safety Lead-in) Recommended Phase II Dose (RP2D)
Recommended Phase II Dose (RP2D) of Fluzoparib+Apatinib
(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
Secondary Outcome Measures
AEs+SAEs
Adverse Events and Serious Adverse Events
PFS by investigator's assessment
Progression-Free-Survival
OS
OS is the time interval from the start of treatment to death due to any reason or lost of follow-up
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
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
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
Disease control rate (DCR)
Complete response + Partial response + Stable disease (CR+PR+SD) based on RECIST 1.1
Duration of response (DoR)
Time from documentation of tumor response to disease progression assessed among patients who had an objective response
Full Information
NCT ID
NCT04296370
First Posted
March 3, 2020
Last Updated
August 6, 2020
Sponsor
Jiangsu HengRui Medicine Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04296370
Brief Title
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
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Recruiting
Study Start Date
July 13, 2020 (Actual)
Primary Completion Date
June 30, 2022 (Anticipated)
Study Completion Date
June 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jiangsu HengRui Medicine Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Treatment in HER2-negative Metastatic Breast Cancer Patients With Germline BRCA Mutation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
474 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Safety Lead-in, Doublet Arm
Arm Type
Experimental
Arm Description
Fluzoparib+Apatinib
Arm Title
Single Arm
Arm Type
Experimental
Arm Description
Fluzoparib
Arm Title
Physician's choice chemotherapy
Arm Type
Active Comparator
Arm Description
Capecitabine or Vinorelbine
Intervention Type
Drug
Intervention Name(s)
Fluzoparib; Apatinib
Intervention Description
Fluzoparib Orally twice daily; Apatinib Orally once daily
Intervention Type
Drug
Intervention Name(s)
Fluzoparib
Intervention Description
Fluzoparib Orally twice daily
Intervention Type
Drug
Intervention Name(s)
Physician's choice chemotherapy
Intervention Description
Investigators will declare one of the following regimens:
Capecitabine Vinorelbine
Primary Outcome Measure Information:
Title
(Safety Lead-in) dose limited toxicity (DLT)
Description
dose limited toxicity (DLT) of Fluzoparib+Apatinib in the first cycle
Time Frame
up to 21 days
Title
(Safety Lead-in) Recommended Phase II Dose (RP2D)
Description
Recommended Phase II Dose (RP2D) of Fluzoparib+Apatinib
Time Frame
up to 21 days
Title
(Phase 3) Progression free survival(PFS) in HER2-negative Metastatic Breast Cancer patients
Description
Defined as progression free survival per RECIST 1.1 criteria according to BIRC criteria
Time Frame
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 Measure Information:
Title
AEs+SAEs
Description
Adverse Events and Serious Adverse Events
Time Frame
from the first drug administration to within 30 days for the last treatment dose
Title
PFS by investigator's assessment
Description
Progression-Free-Survival
Time Frame
up to 30 months
Title
OS
Description
OS is the time interval from the start of treatment to death due to any reason or lost of follow-up
Time Frame
up to 30 months
Title
Patient Reported Outcomes (PROs) assessed by EORTC QLQ C30 questionnaire
Description
Comparison of the Quality of Life in study arms assessed by EORTC QLQ C30 questionnaire
Time Frame
up to 30 months
Title
Time to progression on the next anticancer therapy (PFS2)
Description
From date of start of next anticancer therapy to date of first documented progression of date of death from any cause, whichever comes first
Time Frame
up to 30 months
Title
Objective Response Rate (ORR)
Description
Number of responders Assessed by Modified Response Evaluation Criteria In Solid Tumours (RECIST v1.1) for target lesions assessed by CT or MRI
Time Frame
up to 30 months
Title
Disease control rate (DCR)
Description
Complete response + Partial response + Stable disease (CR+PR+SD) based on RECIST 1.1
Time Frame
up to 30 months
Title
Duration of response (DoR)
Description
Time from documentation of tumor response to disease progression assessed among patients who had an objective response
Time Frame
up to 30 months
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Jiangsu HengRui Medicine Co., Ltd.
City
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Quanren Wang
Phone
+86 18036618570
Email
wangquanren@hrglobe.cn
First Name & Middle Initial & Last Name & Degree
Xiaodi Wang
Phone
+86 13811442099
Email
wangxiaodi@hrglobe.cn
12. IPD Sharing Statement
Plan to Share IPD
No
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A Study of Fluzoparib±Apatinib Versus Chemotherapy Treatment of Physician's Choice in HER2-negative Metastatic Breast Cancer Patients With Germline BRCA Mutation
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