Efficacy and Safety of Fluzoparib Combined With Adjuvant Endocrine Therapy for HR+/HER2- SNF3-subtype Early Breast Cancer (BCTOP-L-A01)

A Prospective, Randomized, Open-label Phase III Clinical Study of the Efficacy and Safety of Fluzoparib Combined With Adjuvant Endocrine Therapy Versus Adjuvant Endocrine Therapy for HR+/HER2- SNF3-subtype Early Breast Cancer (BCTOP-L-A01)

This is a prospective, randomized, open-label phase III clinical study on the efficacy and safety of fluzoparib combined with adjuvant endocrine therapy versus adjuvant endocrine therapy for HR+/HER2- SNF3-subtype early breast cancer.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Fluzoparib; Drug: Anastrozole; Drug: Letrozole; Drug: Exemestane; Drug: Tamoxifen; Drug: Toremifene; Drug: Abemaciclib; Drug: LHRH agonist

Detailed Description

This is a prospective, randomized, open-label phase III clinical study on the efficacy and safety of fluzoparib combined with adjuvant endocrine therapy versus adjuvant endocrine therapy for HR+/HER2- SNF3-subtype early breast cancer.

A total of 766 patients with luminal-type early breast cancer who received surgery at the Fudan University Shanghai Cancer Cancer and were classified as SNF3 (proliferative) by SNF algorithm fusion clustering will be collected for this study. Before enrollment, the primary tumors of the patients were subjected to molecular typing based on H&E slices combined with digital pathology, and subsequent enrollment could be considered if patient pathology was confirmed as SNF3 subtype.

• Study Type: Interventional
• Enrollment (Estimated): 766
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Zhimin Shao, MD, PhD; Phone Number: 8808 +86-021-64175590; Email: zhimingshao@yahoo.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
      • Contact: HuiPing Li, MD; Phone Number: +86-010-88121122
  • Chongqing
    • Chongqing, Chongqing, China, 400030
      • Recruiting
      • Chongqing Cancer Hospital
      • Contact: Xiaohua Zeng, MD; Phone Number: +86-023-65311341
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Recruiting
      • Fujian Medical University Union Hospital
      • Contact: ChuanGui Song, MD; Phone Number: +86-591-83357896
  • Guangdong
    • Guangzhou, Guangdong, China, 519041
      • Recruiting
      • Guangdong Academy of Medical Sciences Guangdong Provincial People's Hospital
      • Contact: Kun Wang, MD; Phone Number: +86-020-83827812
  • Guangzhou
    • Guangdong, Guangzhou, China, 510062
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: ShuSen Wang, MD; Phone Number: +86-020-87343292
  • Jiangsu
    • Nantong, Jiangsu, China, 226006
      • Recruiting
      • Affiliated Hospital of Nantong University
      • Contact: ZhiXian He, MD; Phone Number: +86-513-85052504
      • Contact: SuJie Ni, MD
    • Yangzhou, Jiangsu, China, 225009
      • Recruiting
      • Northern Jiangsu People's Hospital
      • Contact: DeYuan Fu, MD; Phone Number: +86-0514-87373114
  • Liaoning
    • Shenyang, Liaoning, China, 110801
      • Recruiting
      • Liaoning Cancer Hospital & Institute
      • Contact: Tao Shen, MD; Phone Number: +86-024-81916684
      • Contact: Qiang Zhang, MD
    • Shenyang, Liaoning, China, 110002
      • Recruiting
      • The First Hospital of China Medical University
      • Contact: YueE Teng, MD; Phone Number: +86-024-83283333
      • Contact: YingYing Xu, MD
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Zhi-Ming Shao, MD;PhD; Phone Number: +862164175590
    • Shanghai, Shanghai, China, 201204
      • Recruiting
      • Shanghai First Maternity and Infant Hospital
      • Contact: ZhiGang Zhuang, MD; Phone Number: +86-021-20261000
    • Shanghai, Shanghai, China, 200233
      • Recruiting
      • Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University
      • Contact: Zan Shen, MD; Phone Number: +86-021-64369181
  • Shanxi
    • Xi'an, Shanxi, China, 710061
      • Recruiting
      • The First Affiliated Hospital of Xi'an Jiaotong University
      • Contact: Jin Yang, MD; Phone Number: +86-029-85323217
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • West China Hospital of Sichuan University
      • Contact: Ting Luo, MD; Phone Number: +86-028-85422114
  • Zhejiang
    • Ningbo, Zhejiang, China
      • Recruiting
      • Ningbo medical center lihuili hospital
      • Contact: WeiZhu Wu, MD; Phone Number: +86-574-87018701

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Women aged 18-70 years old;
2. ECOG score 0 or 1;
3. ER+/HER2- confirmed by histopathology after early breast cancer surgery（ER positive is defined as immunohistochemistry(IHC) detection of ER ≥ 1% HER2-negative is defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (Fluorescence in situ hybridization (FISH), Chromogenic in situ hybridization (CISH) , or Silver in situ hybridization (SISH)) test is required by local laboratory testing.); definition of SNF3 subtype: SNF3 subtype confirmed by digital pathology of H&E sections;
4. Postoperative pathological stage T2-4N0-3M0;
5. Patients who have previously received neoadjuvant chemotherapy and/or adjuvant chemotherapy;
6. Time of randomization from surgery does not exceed 16 months;
7. Time of endocrine therapy from last non-endocrine anti-tumor treatment does not exceed 12 weeks;
8. Has adequate organ function meeting the following criteria: (1) adequate bone marrow function: hemoglobin ≥ 90 g/L (no blood transfusion within 14 days); absolute neutrophil count ≥ 1.5 x 10^9 /L; platelet count ≥ 100 * 10^9 /L; (2)adequate liver and kidney function: Alanine Aminotransferase (ALT) ≤ 3×upper limit of normal (ULN), Aspartate Aminotransferase (AST) ≤ 3×ULN, Total Bilirubin (TBIL)≤ 1.5×ULN, serum creatinine ≤ 1×ULN，and with endogenous creatinine clearance rate of >50 ml/min (Cockcroft-Gault formula);
9. Patients receiving radiotherapy must recover from the acute phase reaction of radiotherapy, with a washout period of at least 14 days from the end of radiotherapy to randomization;
10. Patients who received chemotherapy in the early stage must recover from acute adverse reactions to chemotherapy ([CTCAE] grade ≤ 1) before randomization, except for hair loss or grade 2 peripheral neuropathy. There is a washout period of at least 21 days from the last chemotherapy administration to randomization (assuming the patient has not received radiotherapy);
11. Patients can take medication orally on their own;
12. Female subjects with fertility are required to use a medically approved contraceptive method during the study treatment
13. Participants voluntarily joined the study, has signed informed consent before any trial related activities are conducted, has good compliance and has agreed to follow-up.

Exclusion Criteria:

1. Has bilateral breast cancer;
2. Has previous history of additional malignancy, with the exception of adequately treated basal cell carcinoma and cervical carcinoma in situ.
3. Has metastatic (Stage 4) breast cancer;
4. Is pregnant, is breast feeding women, or women of childbearing age who cannot practice effective contraceptives;
5. Patients participating in other clinical trials at the same time;
6. Has severe organ dysfunction (cardiopulmonary liver and kidney) insufficiency, left ventricular ejection fraction (LVEF) < 50% (cardiac ultrasound); severe cardio cerebral vascular disease within the 6 months previous of randomization (such as unstable angina, chronic heart failure, uncontrolled hypertension with blood pressure>150/90mmgh, myocardial infarction, or cerebral blood vessel); diabetic patients with poor blood glucose control; patients with severe hypertension;
7. Has known allergy to fluzoparib and excipients.
8. Has severe or uncontrolled infection;
9. Has a history of psychotropic substance abuse and were unable to abandon drug habits, or those with history of mental disorders;
10. The researchers judged patients to be unsuitable for the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fluzoparib+Endocrine Therapy; Fluzoparib 50mg bid orally for 1 year, combined with physician's choice of endocrine therapy as clinically indicated (eg, aromatase inhibitor, tamoxifen, toremifene endocrine therapy for 5 to 10 years; CDK4/6 inhibitor therapy for 2 years; ovarian function suppression with LHRH agonist).	Drug: Fluzoparib; Fluzoparib 50mg bid orally for 1 year.; Drug: Anastrozole; 1mg, qd orally; Drug: Letrozole; 2.5mg, qd orally; Drug: Exemestane; 25mg, qd orally; Drug: Tamoxifen; 10mg, bid orally; Drug: Toremifene; 60mg, qd orally; Drug: Abemaciclib; 150mg/100mg/50mg, bid orally for 2 years; Drug: LHRH agonist; Leuprorelin acetate, goserelin acetate
Active Comparator: Endocrine Therapy; Physician's choice of endocrine therapy as clinically indicated (eg, aromatase inhibitor, tamoxifen, toremifene endocrine therapy for 5 to 10 years; CDK4/6 inhibitor therapy for 2 years; ovarian function suppression with LHRH agonist).	Drug: Anastrozole; 1mg, qd orally; Drug: Letrozole; 2.5mg, qd orally; Drug: Exemestane; 25mg, qd orally; Drug: Tamoxifen; 10mg, bid orally; Drug: Toremifene; 60mg, qd orally; Drug: Abemaciclib; 150mg/100mg/50mg, bid orally for 2 years; Drug: LHRH agonist; Leuprorelin acetate, goserelin acetate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
invasive disease free survival (iDFS)	defined as occurrence of any of the following: ipsilateral invasive breast cancer recurrence, regional invasive breast cancer recurrence, distant recurrence, death attributable to any cause, contralateral invasive breast cancer, or second non-breast invasive cancer.In-situ events are not included.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
distant relapse free survival (DRFS)	the time from operation to the first distant recurrence, and the cases of death without distant recurrence was censored at the time of the death	5 years
overall survival (OS)	the time from treatment to death, regardless of disease recurrence	5 years
Adverse Effects	an undesired harmful effect resulting from a medication or other intervention	5 years
Number of participants with Patient Reported Outcome (PRO)	a health outcome directly reported by the patient who experienced it.	5 years

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2023
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): May 31, 2031

Study Registration Dates

• First Submitted: May 24, 2023
• First Submitted That Met QC Criteria: June 5, 2023
• First Posted (Actual): June 6, 2023

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: adjuvant treatment; fluzoparib; SNF3-subtype
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Poly(ADP-ribose) Polymerase Inhibitors; Hormone Antagonists; Bone Density Conservation Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Letrozole; Tamoxifen; Anastrozole; Exemestane; Toremifene; Fluzoparib
• Other Study ID Numbers: SCHBCC-N056

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No