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

Study Overview
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Brief Summary
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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.

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

Conditions
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TNBC - Triple-Negative Breast Cancer

Intervention / Treatment
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* Drug: Fluzoparib+Paclitaxel
* Drug: Epirubicin+Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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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；

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort1: Epirubicin+Cyclophosphamide<br>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<br>* Fluzoparib+Paclitaxel for 4 cycles if tumor response is SD after 2 cycles of EC induced chemotherapy<br>Drug: Epirubicin+Cyclophosphamide<br>* Epirubicin+Cyclophosphamide<br>|
| Experimental: Cohort2: Fluzoparib+Paclitaxel<br>2 cycles of EC (Epirubicin+Cyclophosphamide) induced chemotherapy, if tumor response is SD: Fluzoparib+Paclitaxel for 4 cycles | Drug: Fluzoparib+Paclitaxel<br>* Fluzoparib+Paclitaxel for 4 cycles if tumor response is SD after 2 cycles of EC induced chemotherapy<br>Drug: Epirubicin+Cyclophosphamide<br>* Epirubicin+Cyclophosphamide<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| tpCR（ypT0/is ypN0） | pCR is defined as the absence of invasive residual disease in the breast and in the axillary lymph nodes (ypT0/is ypN0). | 6 months from the patients enrolled | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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three-negative Breast Cancer with germline BRCA-mutated