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

NCT ID: NCT06255392

Last Updated: 2025-08-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-06-12
• Study Completion Date: 2031-03-31

Brief Summary

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.

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.

Conditions

Fludzoparib" and Anti-angiogenic; HRD-positive/HER2-negative Advanced Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fluzoparib Combined With Apatinib

Fluzoparib combined with Apatinib group: Fluzoparib capsules oral +Apatinib Mesylate oral; each treatment cycle defined as 3 weeks (21 days).

Group Type: EXPERIMENTAL

Fluzoparib

Intervention Type: DRUG

Fluzoparib capsules appropriate dose oral, each treatment cycle defined as 3 weeks (21 days).

Apatinib Mesylate

Intervention Type: DRUG

Apatinib Mesylate oral; each treatment cycle defined as 3 weeks (21 days).

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.

Group Type: ACTIVE_COMPARATOR

Capecitabine tablets

Intervention Type: DRUG

Capecitabine tablets, reasonable dosage with reference to guidelines, each treatment cycle defined as 3 weeks (21 days).

Vinorelbine Tartrate Oral

Intervention Type: DRUG

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).

Eribulin mesylate injection

Intervention Type: DRUG

Eribulin, reasonable dosage with reference to guidelines, each treatment cycle defined as 3 weeks (21 days).

Gemcitabine Hydrochloride

Intervention Type: DRUG

Gemcitabine, reasonable dosage with reference to guidelines, each treatment cycle defined as 3 weeks (21 days).

Paclitaxel-albumin

Intervention Type: DRUG

Paclitaxel-albumin, reasonable dosage with reference to guidelines, each treatment cycle defined as 3 weeks (21 days).

Interventions

Fluzoparib

Fluzoparib capsules appropriate dose oral, each treatment cycle defined as 3 weeks (21 days).

Intervention Type: DRUG

Apatinib Mesylate

Apatinib Mesylate oral; each treatment cycle defined as 3 weeks (21 days).

Intervention Type: DRUG

Capecitabine tablets

Capecitabine tablets, reasonable dosage with reference to guidelines, each treatment cycle defined as 3 weeks (21 days).

Intervention Type: 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).

Intervention Type: DRUG

Eribulin mesylate injection

Eribulin, reasonable dosage with reference to guidelines, each treatment cycle defined as 3 weeks (21 days).

Intervention Type: DRUG

Gemcitabine Hydrochloride

Gemcitabine, reasonable dosage with reference to guidelines, each treatment cycle defined as 3 weeks (21 days).

Intervention Type: DRUG

Paclitaxel-albumin

Paclitaxel-albumin, reasonable dosage with reference to guidelines, each treatment cycle defined as 3 weeks (21 days).

Intervention Type: DRUG

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

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

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jianli Zhao

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Sun Yat Sen Memorial Hospital，Sun Yat sen University

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhao Jianli

Role: CONTACT

zhaojli5@mail.sysu.edu.cn

86-20-34070870

Facility Contacts

Jianli Zhao

Role: primary

zhaojli5@mail.sysu.edu.cn

020-34070870

Ying Wang

Role: backup

wangy556@mail.sysu.edu.cn

020-34070499

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Other Identifiers

SYSKY-2023-1016-04

Identifier Type: -

Identifier Source: org_study_id