Randomized, Open, Controlled, Multicenter Phase III Clinical Study of Fluzoparib in Combination With Apatinib Versus Investigator-Selected Chemotherapy for HRD-Positive/HER2-negative Advanced Breast Cancer

August 12, 2025 updated by: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
This study develops a new therapeutic approach for HER2-negative advanced breast cancer patients without precise treatment targets. The trial aims at extending the combination target therapy involving PARP inhibitors and anti-angiogenesis from only BRCA mutation carriers to all patients with homologous recombination repair defects (HRD-positive). The phase III randomized clinical study will investigate the effectiveness of the combination therapy of PARP inhibitor "fludzoparib" and anti-angiogenic "apatinib" in treating HRD-positive/HER2-negative advanced breast cancers.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Breast cancer is the most prevalent malignant tumor in the world, and 30% of breast cancer patients will enter the advanced stage due to treatment failure. 80% of these patients have HER2-negative subtype breast cancer, which has not yet been found the similar target as HER2, with the median survival time of only 6-20 months. In the past, ovarian cancer patients faced the dilemma of poor survival due to the lack of precise targeted therapy. However, through a series of clinical studies, experts in the field of ovarian cancer have successfully expanded the indications of PARP inhibitor-based combination targeted therapy from the small population of BRCA mutation(20%) to the large population of HRD-positive (Homologous recombination deficiency) (50%), which has significantly prolonged the survival time of patients. Because causes other than BRCA mutations can also cause tumor cells to be "HRD" and thus sensitive to PARP inhibitors, so that HRD-positive patients are likely to benefit. The HRD-positive profile of nearly 50% of the patients could be a potential beneficiary of PARP inhibitor-based targeted therapy. The synergistic effect of PARP inhibitor and anti-angiogenic combination therapy has already been confirmed in preliminary cellular experiments and clinical studies related to ovarian cancer. Further cell-based experiments and preclinical studies have also confirmed the feasibility of the combination targeted therapy in the HRD-positive/HER2-negative subtype of breast cancer. Therefore, we intend to further validate the efficacy and safety of the PARP inhibitor fluazoparib in combination with the antiangiogenic abatinib in a Phase III, randomized, controlled clinical study, in order to provide HRD-positive/HER2-negative breast cancer patients with a better choice of precision targeted therapy.

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510000

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion criteria

The subjects must meet all of the following conditions:

Adult female patients (aged 18 to 70 years) with metastatic breast cancer diagnosed by pathology or imaging; 2) Pathological confirmation of HER2 negative (definition: immunohistochemical result is 0 or + or ++ and in situ hybridization result is negative); 3) The patient's HRD test was positive (definition: BRCA1/2 mutation, or HRD score greater than or equal to 42 points); 4) HR+/HER2- patients who have received endocrine therapy during the metastasis stage; 5) Having received no more than two lines of chemotherapy (or ADC) regimens for metastatic breast cancer in the past; 6) Evaluation of anti-tumor treatment (including chemotherapy /HER2-ADC/TROP2-ADC) for 6-8 cycles to achieve clinical benefit (CR or PR) or SD for 24 weeks or more; 7) ECOG physical condition score ≤2 points, and the expected survival period is no less than 3 months; 8) At least one measurable lesion was found in the imaging examination within 2 weeks before enrollment. Or simple bone metastasis lesion; 9) At the time of enrollment, the previous treatment-related toxicity must be remitted to NCI CTCAE (Version 5.0) ≤1 degree (except for alopecia or other toxicities that the investigator deems to pose no risk to the patient's safety).

10) Adequate bone marrow functional reserve:

  1. White blood cell count (WBC) ≥3.0×10^9 / L
  2. Neutrophil count (ANC) ≥1.5×10^9 / L
  3. Platelet count (PLT) ≥70×10^9 / L 11) Liver, kidney and heart function tests are basically normal (based on the normal values in the laboratories of each research center) :

a. Total bilirubin (TBIL) ≤3× upper limit of normal (ULN) b. Alanine aminotransferase and aspartate aminotransferase (ALT/AST) ≤2.5×ULN (≤5 ×ULN for patients with liver metastasis) c. Serum creatinine ≤1.5×ULN or creatinine clearance rate (Ccr) ≥60 ml/min; d.Left ventricular ejection fraction (LVEF) ≥ 55%, e. QTcF(Fridericia correction) ≤ 470 ms. 12) Be able to understand the research process, voluntarily participate in this research, and sign the informed consent form.

Exclusion Criteria

If a subject experiences any of the following situations, they will not be eligible to participate in this study:

  1. Patients with HR+/ HER2-MBC who have not received endocrine therapy before;
  2. Has not received any treatment for metastatic breast cancer;
  3. Received more than two chemotherapy regimens for metastatic breast cancer;
  4. Patients who are known to be allergic to the active ingredient or other ingredients of the investigational drug.
  5. Pregnant or lactating women, and women of childbearing age who refused to take effective contraceptive measures during the study period.
  6. Those with severe heart disease or discomfort, expected to be unable to tolerate chemotherapy, including but not limited to: fatal arrhythmia or higher-grade atrioventricular block, unstable angina pectoris, clinically significant valvular heart disease, electrocardiogram showing transmural myocardial infarction, uncontrollable hypertension;
  7. Any other circumstances where the researcher deems the patient unsuitable for participation in this study, any concomitant diseases or conditions that may interfere with participation in the study, or any serious medical conditions that may affect the safety of the subjects (such as uncontrollable heart disease, hypertension, active or uncontrollable infection, active hepatitis B virus infection).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Fluzoparib Combined With Apatinib
Fluzoparib combined with Apatinib group: Fluzoparib capsules oral +Apatinib Mesylate oral; each treatment cycle defined as 3 weeks (21 days).
Drug: Fluzoparib
Fluzoparib capsules appropriate dose oral, each treatment cycle defined as 3 weeks (21 days).
Drug: Apatinib Mesylate
Apatinib Mesylate oral; each treatment cycle defined as 3 weeks (21 days).
Active Comparator: Chemotherapy selected by the investigator
Control group: Control group: patients receive oral Capecitabine tablets, Vinorelbine Tartrate Capsules, or use intravenous Paclitaxel for Injection (Albumin Bound), Gemcitabine Hydrochloride for Injection, or other drugs selected by the investigator.
Drug: Capecitabine tablets
Capecitabine tablets, reasonable dosage with reference to guidelines, each treatment cycle defined as 3 weeks (21 days).
Drug: Vinorelbine Tartrate Oral
For the first three courses: reasonable dosage with reference to guidelines. After 3 courses of medication, it is recommended to increase the dose of vinorelbine tartrate once a week. Each treatment cycle defined as 3 weeks (21 days).
Drug: Eribulin mesylate injection
Eribulin, reasonable dosage with reference to guidelines, each treatment cycle defined as 3 weeks (21 days).
Drug: Gemcitabine Hydrochloride
Gemcitabine, reasonable dosage with reference to guidelines, each treatment cycle defined as 3 weeks (21 days).
Drug: Paclitaxel-albumin
Paclitaxel-albumin, reasonable dosage with reference to guidelines, each treatment cycle defined as 3 weeks (21 days).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival，PFS（Independent Review Committee）
Time Frame: 2 years
The time from the beginning of treatment to the progression or death of the patient
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival，PFS（Investigator）
Time Frame: 2 years
The time from the beginning of treatment to the progression or death of the patient
2 years
Objective Response Rate，ORR
Time Frame: 2 years
the proportion of patients with a tumor volume reduction of ≥30% and a minimum timeframe according to accepted response evaluation criteria (e.g., RECIST version 1.1 in solid tumors), including cases of complete response (CR) and partial response (PR).
2 years
Clinical Benefit Rate，CBR
Time Frame: 2 years
Proportion of confirmed complete response, partial response, or stable disease ≥ 24 weeks.
2 years
Disease Control Rate， DCR
Time Frame: 2 years
Proportion of patients with stable or shrinking tumor size，sum of the proportions of complete remission (CR), partial remission (PR) and stable disease (SD)
2 years
Overall survival time ，OS
Time Frame: 2 years
The time from the start of randomization to death due to any cause.
2 years
the rate of adverse events
Time Frame: 2 years
The probability and severity of adverse reactions, and the extent and incidence of AEs were assessed according to CTCAE.
2 years
Quality of life scale score，QoL
Time Frame: 2 years
The function or quality of a patient's physical, psychological, and social adaptability is also known as quality, which is assessed according to the EROTC C30 scale.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Investigators

  • Principal Investigator: Jianli Zhao, Sun Yat-sen Memorial Hospital of Sun Yat-sen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 12, 2024

Primary Completion (Estimated)

March 1, 2031

Study Completion (Estimated)

March 1, 2031

Study Registration Dates

First Submitted

February 5, 2024

First Submitted That Met QC Criteria

February 5, 2024

First Posted (Actual)

February 13, 2024

Study Record Updates

Last Update Posted (Estimated)

August 15, 2025

Last Update Submitted That Met QC Criteria

August 12, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SYSKY-2023-1016-04

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

As personal information of patients is involved, we decided not to share individual participant data of patients.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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