Clinical trial NCT06375707: Efficacy and Safety of Ribociclib in Combination With NSAI Versus Physician's Choice of Chemotherapy Sequential Endocrine Therapy in HR+/HER2- Advanced Breast Cancer
Official title: Efficacy and Safety of Ribociclib in Combination With NSAI Versus Physician's Choice of Chemotherapy Sequential Endocrine Therapy in HR+/HER2- Advanced Breast Cancer: a Phase II Randomised Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Advanced Breast Cancer
Keywords: HR positive /HER2 negative
Ribociclib
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
Collaborators: name: Zhejiang Cancer Hospital
First posted: 2024-04-19
Enrollment: 144
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Evaluate the efficacy and safety of Ribociclib in combination with NSAI versus physician's choice of chemotherapy sequential endocrine therapy in HR+/HER2- advanced breast cancer.

Detailed description: The main goal of this clinical trial is to compare in the efficacy of Ribociclib in combination with NSAI versus physician's choice of chemotherapy sequential endocrine therapy in HR+/HER2- advanced breast cancer and evaluate the PCR DFS,OS and safety of the subjects. The main question it aims is comparing the efficacy and safety of first-line application of CDK4/6 inhibitors combined with initial endocrine therapy versus sequential endocrine therapy after chemotherapy induction therapy in HR+/HER2-advanced breast cancer with rapidly progressive disease.

This study is planned to include 144 patients with HR+/HER2-advanced breast cancer with rapidly progressive disease between November 2023 and November 2025 who meet the entry criteria. A central dynamic randomisation system was used for 1:1 allocation to the repositories combined with NSAI treatment group and the physician's choice of chemotherapy sequential repositories combined with NSAI treatment group, with stratification factors including: level of HR expression, and presence of liver/lung metastases.

Eligibility criteria: Inclusion Criteria:

1. Patient is an adult female ≥ 18 years old at the time of informed consent.
2. ECGO rating 0-2.
3. Histologically confirmed recurrent or metastatic breast cancer, including patients initially diagnosed as stage IV or locally advanced inoperable patients.
4. Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer based on the most recently analyzed tissue sample and all tested by local laboratory. ER should be more than 10% ER positive by local laboratory testing.
5. Patient has HER2-negative breast cancer 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 (FISH, CISH, or SISH) test is required by local laboratory testing and based on the most recently analyzed tissue sample.
6. Determination by the physician that the patient is in a rapid disease progression situation:

   * Symptomatic visceral metastases
   * Rapid progression of disease or impending visceral compromise.
   * Markedly symptomatic non visceral disease if the treating physician opt to give chemotherapy for rapid palliation of patients symptoms.
7. Patient hasn't received systemic anti-cancer therapy at the stage of recurrence/metastasis.
8. Patient must have at least one measurable lesion (according to RECIST 1.1 criteria)
9. Postmenopausal or pre/perimenopausal female patients are eligible for enrolment; pre or perimenopausal female patients must be willing to receive LHRHa during the study period.
10. All patients were required to meet the following laboratory biochemical values prior to enrolment:

    * Haematology: Hb ≥90 g/L, WBC ≥3.5×109/L, ANC ≥1.5×109/L, PLT ≥100×109/L;
    * Renal function: serum creatinine ≤ upper limit of normal value;
    * Liver function: for those without liver metastases, AST, ALT, ALP ≤2.5 times the upper limit of normal values, and ≤1.25 x the upper limit of normal values for total bilirubin; for those with liver metastases, AST, ALT, ALP ≤ 5 times the upper limit of normal value, and total bilirubin ≤ 1.5 x upper limit of normal value.

Exclusion Criteria:

1. Patient has received systemic anti-cancer therapy at the stage of recurrence/metastasis.
2. Those who have been treated with CDK4/6 inhibitors in the neoadjuvant/adjuvant phase.
3. Patients those with symptomatic CNS metastases.
4. Patient has a history of clinically symptomatic cardiovascular, hepatic, respiratory, renal and haemato-endocrine system or neuropsychiatric disorders.
5. Patient has a serious concomitant disease, such as an infectious disease; has multiple factors that affect the oral administration and absorption of the drug.
6. Pregnant or lactating women (women of childbearing age must have had a negative pregnancy test within 14 days prior to the first dose; if positive, pregnancy must be ruled out by ultrasound).
7. Patients in poor general condition who cannot tolerate chemotherapy treatment.
8. The investigator considers the patient unsuitable for entry into this study.

Primary outcomes:
measure: Progression Free Survival
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Secondary outcomes:
measure: Progression Free Survival2
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
measure: Time to treatment failure
timeFrame: From randomization to treatment failure or withdrawal from the trial; reasons for withdrawal can be patient request, disease progression, death, or adverse events, whichever came first, assessed up to 100 months
measure: Overall response rate (ORR)
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
measure: Overall survival(OS)
timeFrame: From date of randomization until the date of death from any cause, assessed up to 100 months
measure: Time To Response (TTR)
timeFrame: From the date of randomization to the first documented response of either CR or PR, whichever came first, assessed up to 100 months
measure: Clinical benefit rate(CBR)
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
measure: Change from baseline in the global health status/QOL scale score by using FACT-B questionnaire
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
measure: Frequency/severity of adverse events, lab abnormalities
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Jiangsu Provincial People's Hospital
state: Jiangsu
Study officials:
References: