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

Breast Cancer Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05891093
• Other study ID #: SCHBCC-N056
• Status: Recruiting
• Phase: Phase 3
• Start date: June 1, 2023
• Est. completion date: May 31, 2031

Study information

• Verified date: February 2024
• Source: Fudan University
• Contact: Zhimin Shao, MD, PhD
• Phone: +86-021-64175590
• Email: zhimingshao[@]yahoo.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 766
• Est. completion date: May 31, 2031
• Est. primary completion date: May 31, 2028
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Fluzoparib
Fluzoparib 50mg bid orally for 1 year.
• Anastrozole
1mg, qd orally
• Letrozole
2.5mg, qd orally
• Exemestane
25mg, qd orally
• Tamoxifen
10mg, bid orally
• Toremifene
60mg, qd orally
• Abemaciclib
150mg/100mg/50mg, bid orally for 2 years
• LHRH agonist
Leuprorelin acetate, goserelin acetate

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	Chongqing Cancer Hospital	Chongqing	Chongqing
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Sun Yat-sen University Cancer Center	Guangdong	Guangzhou
China	Guangdong Academy of Medical Sciences Guangdong Provincial People's Hospital	Guangzhou	Guangdong
China	Affiliated Hospital of Nantong University	Nantong	Jiangsu
China	Ningbo Medical Center Lihuili Hospital	Ningbo	Zhejiang
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Shanghai First Maternity and Infant Hospital	Shanghai	Shanghai
China	Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University	Shanghai	Shanghai
China	Liaoning Cancer Hospital & Institute	Shenyang	Liaoning
China	The First Hospital of China Medical University	Shenyang	Liaoning
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shanxi
China	Northern Jiangsu People's Hospital	Yangzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	overall survival (OS)	the time from treatment to death, regardless of disease recurrence	5 years
Secondary	Adverse Effects	an undesired harmful effect resulting from a medication or other intervention	5 years
Secondary	Number of participants with Patient Reported Outcome (PRO)	a health outcome directly reported by the patient who experienced it.	5 years