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

NCT06255392 | Recruiting Phase 3

• 1 other identifier: SYSKY-2023-1016-04
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival，PFS（Independent Review Committee）

  The time from the beginning of treatment to the progression or death of the patient

  2 years

Secondary Outcomes (7)

• Progression Free Survival，PFS（Investigator）

  2 years

• Objective Response Rate，ORR

  2 years

• Clinical Benefit Rate，CBR

  2 years

• Disease Control Rate， DCR

  2 years

• Overall survival time ，OS

  2 years

Study Arms (2)

Fluzoparib Combined With Apatinib

EXPERIMENTAL

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

Drug: Fluzoparib; Drug: Apatinib Mesylate

Chemotherapy selected by the investigator

ACTIVE COMPARATOR

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; Drug: Vinorelbine Tartrate Oral; Drug: Eribulin mesylate injection; Drug: Gemcitabine Hydrochloride; Drug: Paclitaxel-albumin

Interventions

Fluzoparib DRUG

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

Fluzoparib Combined With Apatinib

Apatinib Mesylate DRUG

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

Fluzoparib Combined With Apatinib

Capecitabine tablets DRUG

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

Chemotherapy selected by the investigator

Vinorelbine Tartrate Oral 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).

Chemotherapy selected by the investigator

Eribulin mesylate injection DRUG

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

Chemotherapy selected by the investigator

Gemcitabine Hydrochloride DRUG

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

Chemotherapy selected by the investigator

Paclitaxel-albumin DRUG

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

Chemotherapy selected by the investigator

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• \) Adequate bone marrow functional reserve:
• White blood cell count (WBC) ≥3.0×10\^9 / L
• Neutrophil count (ANC) ≥1.5×10\^9 / L
• 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.

You may not qualify if:

• If a subject experiences any of the following situations, they will not be eligible to participate in this study:
• Patients with HR+/ HER2-MBC who have not received endocrine therapy before;
• Has not received any treatment for metastatic breast cancer;
• Received more than two chemotherapy regimens for metastatic breast cancer;
• Patients who are known to be allergic to the active ingredient or other ingredients of the investigational drug.
• Pregnant or lactating women, and women of childbearing age who refused to take effective contraceptive measures during the study period.
• 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;
• 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).

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead

Study Sites (1)

Sun Yat Sen Memorial Hospital，Sun Yat sen University

Guangzhou, Guangdong, 510000, China

RECRUITING

Related Publications (10)

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  PMID: 30110579 BACKGROUND

• Iglehart JD, Silver DP. Synthetic lethality--a new direction in cancer-drug development. N Engl J Med. 2009 Jul 9;361(2):189-91. doi: 10.1056/NEJMe0903044. Epub 2009 Jun 24. No abstract available.

  PMID: 19553640 BACKGROUND

• Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. doi: 10.1056/NEJMoa1706450. Epub 2017 Jun 4.

  PMID: 28578601 BACKGROUND

• Gonzalez-Martin A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, McCormick C, Lorusso D, Hoskins P, Freyer G, Baumann K, Jardon K, Redondo A, Moore RG, Vulsteke C, O'Cearbhaill RE, Lund B, Backes F, Barretina-Ginesta P, Haggerty AF, Rubio-Perez MJ, Shahin MS, Mangili G, Bradley WH, Bruchim I, Sun K, Malinowska IA, Li Y, Gupta D, Monk BJ; PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2391-2402. doi: 10.1056/NEJMoa1910962. Epub 2019 Sep 28.

  PMID: 31562799 BACKGROUND

• Ray-Coquard I, Pautier P, Pignata S, Perol D, Gonzalez-Martin A, Berger R, Fujiwara K, Vergote I, Colombo N, Maenpaa J, Selle F, Sehouli J, Lorusso D, Guerra Alia EM, Reinthaller A, Nagao S, Lefeuvre-Plesse C, Canzler U, Scambia G, Lortholary A, Marme F, Combe P, de Gregorio N, Rodrigues M, Buderath P, Dubot C, Burges A, You B, Pujade-Lauraine E, Harter P; PAOLA-1 Investigators. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2416-2428. doi: 10.1056/NEJMoa1911361.

  PMID: 31851799 BACKGROUND

• Sun C, Yin J, Fang Y, Chen J, Jeong KJ, Chen X, Vellano CP, Ju Z, Zhao W, Zhang D, Lu Y, Meric-Bernstam F, Yap TA, Hattersley M, O'Connor MJ, Chen H, Fawell S, Lin SY, Peng G, Mills GB. BRD4 Inhibition Is Synthetic Lethal with PARP Inhibitors through the Induction of Homologous Recombination Deficiency. Cancer Cell. 2018 Mar 12;33(3):401-416.e8. doi: 10.1016/j.ccell.2018.01.019.

  PMID: 29533782 BACKGROUND

• Severson TM, Wolf DM, Yau C, Peeters J, Wehkam D, Schouten PC, Chin SF, Majewski IJ, Michaut M, Bosma A, Pereira B, Bismeijer T, Wessels L, Caldas C, Bernards R, Simon IM, Glas AM, Linn S, van 't Veer L. The BRCA1ness signature is associated significantly with response to PARP inhibitor treatment versus control in the I-SPY 2 randomized neoadjuvant setting. Breast Cancer Res. 2017 Aug 25;19(1):99. doi: 10.1186/s13058-017-0861-2.

  PMID: 28851423 BACKGROUND

• Gruber JJ, Afghahi A, Timms K, DeWees A, Gross W, Aushev VN, Wu HT, Balcioglu M, Sethi H, Scott D, Foran J, McMillan A, Ford JM, Telli ML. A phase II study of talazoparib monotherapy in patients with wild-type BRCA1 and BRCA2 with a mutation in other homologous recombination genes. Nat Cancer. 2022 Oct;3(10):1181-1191. doi: 10.1038/s43018-022-00439-1. Epub 2022 Oct 17.

  PMID: 36253484 BACKGROUND

• Liu JF, Barry WT, Birrer M, Lee JM, Buckanovich RJ, Fleming GF, Rimel BJ, Buss MK, Nattam SR, Hurteau J, Luo W, Curtis J, Whalen C, Kohn EC, Ivy SP, Matulonis UA. Overall survival and updated progression-free survival outcomes in a randomized phase II study of combination cediranib and olaparib versus olaparib in relapsed platinum-sensitive ovarian cancer. Ann Oncol. 2019 Apr 1;30(4):551-557. doi: 10.1093/annonc/mdz018.

  PMID: 30753272 BACKGROUND

• Liu JF, Barry WT, Birrer M, Lee JM, Buckanovich RJ, Fleming GF, Rimel B, Buss MK, Nattam S, Hurteau J, Luo W, Quy P, Whalen C, Obermayer L, Lee H, Winer EP, Kohn EC, Ivy SP, Matulonis UA. Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. Lancet Oncol. 2014 Oct;15(11):1207-14. doi: 10.1016/S1470-2045(14)70391-2. Epub 2014 Sep 10.

  PMID: 25218906 BACKGROUND

MeSH Terms

Interventions

fluzoparib; apatinib; Capecitabine; Vinorelbine; eribulin; Gemcitabine

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Jianli Zhao

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhao Jianli

CONTACT

86-20-34070870; zhaojli5@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2024
• First Posted: February 13, 2024
• Study Start: June 12, 2024
• Primary Completion (Estimated): March 1, 2031
• Study Completion (Estimated): March 1, 2031
• Last Updated: August 15, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)