Clinical trial NCT05891093: Efficacy and Safety of Fluzoparib Combined With Adjuvant Endocrine Therapy for HR+/HER2- SNF3-subtype Early Breast Cancer (BCTOP-L-A01)
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Breast Cancer
Keywords: fluzoparib
adjuvant treatment
SNF3-subtype
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2023-06-06
Enrollment: 766
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: invasive disease free survival (iDFS)
timeFrame: 5 years
Secondary outcomes:
measure: distant relapse free survival (DRFS)
timeFrame: 5 years
measure: overall survival (OS)
timeFrame: 5 years
measure: Adverse Effects
timeFrame: 5 years
measure: Number of participants with Patient Reported Outcome (PRO)
timeFrame: 5 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing Cancer Hospital
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Guangzhou
country: China
facility: Guangdong Academy of Medical Sciences Guangdong Provincial People's Hospital
state: Guangdong
city: Guangdong
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangzhou
city: Nantong
country: China
facility: Affiliated Hospital of Nantong University
state: Jiangsu
city: Yangzhou
country: China
facility: Northern Jiangsu People's Hospital
state: Jiangsu
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: Liaoning Cancer Hospital & Institute
state: Liaoning
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai First Maternity and Infant Hospital
state: Shanghai
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Ningbo
country: China
facility: Ningbo Medical Center Lihuili Hospital
state: Zhejiang
Study officials:
References: