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

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

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.

Study Overview

• Status: Recruiting
• Conditions: TNBC - Triple-Negative Breast Cancer
• Intervention / Treatment: Drug: Fluzoparib+Paclitaxel; Drug: Epirubicin+Cyclophosphamide

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaoan Liu, Professor; Phone Number: 025-68308162; Email: liuxiaoan@126.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Recruiting
      • JiangSu Province Hospital/ The First Affiliated Hospital of Nanjing Medical University
      • Contact: Xiaoan Liu, Professor; Phone Number: 025-68308162; Email: liuxiaoan@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Women ≥ 18 and ≤ 70 years of age with treatment-naïve breast cancer

2. 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%

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

Exclusion Criteria:

1. Patients with metastatic breast cancer or bilateral breast cancer or inflammatory breast cancer;
2. 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;
3. Previously received PARPi therapy;
4. History of another primary malignancy;
5. Confirmed history of heart failure or systolic dysfunction (LVEF < 50%); high risk uncontrolled cardiac arrhythmias, such as atrial tachycardia;
6. Female patients who are pregnant or lactating;
7. History of allergy to drugs in this study；

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Principal Investigator: Xiaoan Liu, Professor, JiangSu Province Hospital/ The First Affiliated Hospital of Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2023
• Primary Completion (Anticipated): June 1, 2025
• Study Completion (Anticipated): June 1, 2026

Study Registration Dates

• First Submitted: April 18, 2023
• First Submitted That Met QC Criteria: April 27, 2023
• First Posted (Actual): April 28, 2023

Study Record Updates

• Last Update Posted (Actual): April 28, 2023
• Last Update Submitted That Met QC Criteria: April 27, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: three-negative Breast Cancer with germline BRCA-mutated
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Cyclophosphamide; Paclitaxel; Epirubicin
• Other Study ID Numbers: MA-BC-II-050

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