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

Sponsor

Fudan University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05891093

Collaborator

(none)

766

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Fluzoparib Drug: Anastrozole Drug: Letrozole Drug: Exemestane Drug: Tamoxifen Drug: Toremifene Drug: Abemaciclib Drug: LHRH agonist	Phase 3

Detailed Description

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 Design

Study Type:

Interventional

Anticipated Enrollment :

766 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Jun 1, 2023

Anticipated Primary Completion Date :

May 31, 2028

Anticipated Study Completion Date :

May 31, 2031

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

invasive disease free survival (iDFS) [5 years]
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.

Secondary Outcome Measures

distant relapse free survival (DRFS) [5 years]
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
overall survival (OS) [5 years]
the time from treatment to death, regardless of disease recurrence
Adverse Effects [5 years]
an undesired harmful effect resulting from a medication or other intervention
Number of participants with Patient Reported Outcome (PRO) [5 years]
a health outcome directly reported by the patient who experienced it.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Women aged 18-70 years old;
ECOG score 0 or 1;
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;
Postoperative pathological stage T2-4N0-3M0;
Patients who have previously received neoadjuvant chemotherapy and/or adjuvant chemotherapy;
Time of randomization from surgery does not exceed 16 months;
Time of endocrine therapy from last non-endocrine anti-tumor treatment does not exceed 12 weeks;
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);
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;
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);
Patients can take medication orally on their own;
Female subjects with fertility are required to use a medically approved contraceptive method during the study treatment
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:

Has bilateral breast cancer;
Has previous history of additional malignancy, with the exception of adequately treated basal cell carcinoma and cervical carcinoma in situ.
Has metastatic (Stage 4) breast cancer;
Is pregnant, is breast feeding women, or women of childbearing age who cannot practice effective contraceptives;
Patients participating in other clinical trials at the same time;
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;
Has known allergy to fluzoparib and excipients.
Has severe or uncontrolled infection;
Has a history of psychotropic substance abuse and were unable to abandon drug habits, or those with history of mental disorders;
The researchers judged patients to be unsuitable for the study.