Neoadjuvant Fluzoparib in Germline BRCA-mutated Three-negative Breast Cancer Breast Cancer

Sponsor

The First Affiliated Hospital with Nanjing Medical University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05834582

Collaborator

Jiangsu HengRui Medicine Co., Ltd. (Industry)

Enrollment

Location

Arms

37.8

Anticipated Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Although many PARP inhibitors did not improve pCR in neoadjuvant studies, it is not an unchallenged conclusion that TNBC does not benefit from use of PARP inhibitors in neoadjuvant therapy.This study is an open-label, two-cohort, multicenter trial. 60 patients with germline BRCA-mutated three-negative early breast cancer are planned to be enrolled and treated with fluzoparib combined with chemotherapy according to tumor response after EC (epirubicin and cyclophosphamide) for 2 cycles.

Condition or Disease	Intervention/Treatment	Phase
TNBC - Triple-Negative Breast Cancer	Drug: Fluzoparib+Paclitaxel Drug: Epirubicin+Cyclophosphamide	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Neoadjuvant Fluzoparib Combined With Chemotherapy in Germline BRCA-mutated Three-negative Breast Cancer Breast Cancer: an Open, Multicenter, Cohort Trial

Actual Study Start Date :

Apr 8, 2023

Anticipated Primary Completion Date :

Jun 1, 2025

Anticipated Study Completion Date :

Jun 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort1: Epirubicin+Cyclophosphamide 2 cycles of EC (Epirubicin+Cyclophosphamide) induced chemotherapy, if tumor response is CR or PR: Epirubicin+Cyclophosphamide for 2 cycles Fluzoparib+Paclitaxel for 2 cycles	Drug: Fluzoparib+Paclitaxel Fluzoparib+Paclitaxel for 4 cycles if tumor response is SD after 2 cycles of EC induced chemotherapy Drug: Epirubicin+Cyclophosphamide Epirubicin+Cyclophosphamide
Experimental: Cohort2: Fluzoparib+Paclitaxel 2 cycles of EC (Epirubicin+Cyclophosphamide) induced chemotherapy, if tumor response is SD: Fluzoparib+Paclitaxel for 4 cycles	Drug: Fluzoparib+Paclitaxel Fluzoparib+Paclitaxel for 4 cycles if tumor response is SD after 2 cycles of EC induced chemotherapy Drug: Epirubicin+Cyclophosphamide Epirubicin+Cyclophosphamide

Arm

Intervention/Treatment

Experimental: Cohort1: Epirubicin+Cyclophosphamide

2 cycles of EC (Epirubicin+Cyclophosphamide) induced chemotherapy, if tumor response is CR or PR: Epirubicin+Cyclophosphamide for 2 cycles Fluzoparib+Paclitaxel for 2 cycles

Drug: Fluzoparib+Paclitaxel

Fluzoparib+Paclitaxel for 4 cycles if tumor response is SD after 2 cycles of EC induced chemotherapy

Drug: Epirubicin+Cyclophosphamide

Epirubicin+Cyclophosphamide

Experimental: Cohort2: Fluzoparib+Paclitaxel

2 cycles of EC (Epirubicin+Cyclophosphamide) induced chemotherapy, if tumor response is SD: Fluzoparib+Paclitaxel for 4 cycles

Drug: Fluzoparib+Paclitaxel

Fluzoparib+Paclitaxel for 4 cycles if tumor response is SD after 2 cycles of EC induced chemotherapy

Drug: Epirubicin+Cyclophosphamide

Epirubicin+Cyclophosphamide

Outcome Measures

Primary Outcome Measures

tpCR（ypT0/is ypN0） [6 months from the patients enrolled]
pCR is defined as the absence of invasive residual disease in the breast and in the axillary lymph nodes (ypT0/is ypN0).

Secondary Outcome Measures

Event-free Survival (EFS) as assessed by Investigator [Up to approximately 3 years]
EFS is defined as the time from enrollment to disease progression or death due to any cause
AEs and SAEs [From enrollment to the surgery (approximately 6 months)]
adverse events and serious adverse events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Women ≥ 18 and ≤ 70 years of age with treatment-naïve breast cancer
Histopathologically confirmed early or locally advanced three-negative invasive breast cancer as defined by the ASCO/CAP guidelines while meeting the following conditions:

HER2 negative: IHC 0/1 + or IHC2 + but ISH negative; ER and/or PR negative (not eligible for endocrine therapy): IHC nuclear staining ≤ 1%

Tumor stage: II-III: Primary tumor size: ≥ 2cm
ECOG score 0 ~ 1;
Centrally confirmed BRCA1 or BRCA2 germline mutation;
Eligible level of organ function

Exclusion Criteria:

Patients with metastatic breast cancer or bilateral breast cancer or inflammatory breast cancer;
Participated in other drug trials or received any anti-tumor therapy within 4 weeks before enrollment, including endocrine therapy, immunotherapy, biological therapy or tumor embolization;
Previously received PARPi therapy;
History of another primary malignancy;
Confirmed history of heart failure or systolic dysfunction (LVEF < 50%); high risk uncontrolled cardiac arrhythmias, such as atrial tachycardia;
Female patients who are pregnant or lactating;
History of allergy to drugs in this study；