This phase II study focuses on women with rapidly progressive hormone receptor-positive and HER2-negative advanced breast cancer, including patients with symptomatic visceral metastases, rapidly increasing tumor burden, impending organ dysfunction, or highly symptomatic non-visceral disease. These patients often require prompt and effective systemic treatment. The purpose of the study is to determine whether first-line ribociclib combined with endocrine therapy can provide effective and rapid tumor control compared with chemotherapy-based treatment. Women in the prospective study group receive ribociclib plus endocrine therapy, with ovarian function suppression when clinically indicated. Their outcomes are compared with data from patients previously treated at the same participating hospitals with combination chemotherapy, with or without subsequent endocrine maintenance therapy. The main outcome is the objective response rate, defined as the proportion of patients whose tumors shrink or disappear. Other outcomes include progression-free survival, overall survival, clinical benefit, time to response, treatment safety, and quality of life.
This study focuses on patients with rapidly progressive hormone receptor-positive, HER2-negative advanced breast cancer, a population for whom prompt systemic disease control is clinically important. Rapid progression may include symptomatic visceral metastases, rapidly increasing tumor burden, impending organ dysfunction, or highly symptomatic non-visceral disease. The study was initially designed as a prospective, multicenter, randomized phase II trial. Owing to difficulties in prospectively recruiting patients to the chemotherapy control arm, the protocol was amended to include a prospective ribociclib plus endocrine therapy cohort and a retrospective external control cohort. Following statistical consultation, objective response rate was designated as the primary endpoint, with progression-free survival retained as a key secondary endpoint. Under the amended design, eligible patients receiving first-line ribociclib plus endocrine therapy are enrolled prospectively. Their outcomes are compared with an external control cohort selected from patients treated at the same participating hospitals who received first-line combination chemotherapy, with or without subsequent endocrine maintenance therapy. External control patients are identified from electronic medical records and institutional clinical databases and are required to meet eligibility criteria comparable to those applied to the prospective cohort. The historical control period extends from January 2020 to January 2024. Objective response rate was designated as the primary endpoint because it directly evaluates early antitumor activity in this phase II setting and was used as the basis for the revised sample-size calculation. Progression-free survival remains a key secondary endpoint. To reduce confounding associated with the nonrandomized external-control design, the study will use predefined eligibility criteria, standardized outcome definitions, and propensity score-based methods, including inverse probability weighting and propensity score matching, with additional multivariable analyses as appropriate. The major protocol amendment was incorporated into Protocol Version 4.0, dated 28 December 2025, and was approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University on 21 January 2026 under approval number 2023-SR-880.A1.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
74
Ribociclib is administered orally at a dose of 600 mg once daily on Days 1-21 of each 28-day treatment cycle. It is given in combination with investigator-selected endocrine therapy, including anastrozole, letrozole, exemestane, or fulvestrant. Premenopausal or perimenopausal patients also receive ovarian function suppression with goserelin when indicated. Treatment continues until disease progression, unacceptable toxicity, death, withdrawal of consent, or another protocol-defined reason for discontinuation. Dose interruption or reduction is permitted according to protocol-specified toxicity management criteria.
Jiangsu Provincial People's Hospital
Nanjing, Jiangsu, China
Overall response rate (ORR)
Overall response rate (ORR) is defined as the proportion of patients whose best overall response is either complete response (CR) or partial response (PR), as per local review and according to RECIST 1.1.
Time frame: 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
Progression Free Survival
Progression-free survival is defined as the time from the date of randomization to the date of the first documented progression as per local review and according to RECIST 1.1 or death due to any cause.
Time frame: 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
Overall survival(OS)
Overall survival is defined as the time from the date of randomization to the date of death due to any cause.
Time frame: From date of randomization until the date of death from any cause, assessed up to 100 months
Progression Free Survival2
Refers to the time from randomization to disease progression or death after a patient enters a clinical trial and receives second-line therapy.
Time frame: 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
Time to treatment failure
Time to treatment failure is defined as the time from the date of randomization/start of treatment to the earliest of date of progression, date of death due to any cause, change to other anti-cancer therapy, or date of discontinuation due to reasons other than 'Protocol violation' or 'Administrative problems'.
Time frame: 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
Time To Response (TTR)
Time to response is defined as the time from the date of randomization to the first documented response of either CR or PR, which must be subsequently confirmed, as defined by RECIST 1.1.
Time frame: From the date of randomization to the first documented response of either CR or PR, whichever came first, assessed up to 100 months
Clinical benefit rate(CBR)
Clinical benefit rate is defined as the proportion of patients with a best overall response of CR, or PR or stable disease, lasting for a duration of at least 24 weeks, as defined by RECIST 1.1.
Time frame: 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
Change from baseline in the global health status/QOL scale score by using FACT-B questionnaire
Functional Assessment of Cancer Therapy - Breast (FACT-B) will be collected to assess health-related QoL, health status, functioning, disease symptoms, side effects, and cancer-related pain. Descriptive statistics will be used to summarize the overall score at each scheduled assessment time point. Additionally, change from baseline at the time of each assessment will be summarized. The distribution of time to definitive 10% deterioration in the global health status from FACT-B questionnaire will be assessed in the two treatment arms. Scores range from 0 to 4. no subscale. 0 score is the worst for social/family and functional wellbeing and 4 is the worst for physical, emotional wellbeing and additional concerns.
Time frame: 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
Frequency/severity of adverse events, lab abnormalities
Safety of ribociclib in combination with NSAI and OFS, and combination chemotherapies
Time frame: 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
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.