First-Line Ribociclib Plus Endocrine Therapy Versus Chemotherapy With or Without Subsequent Endocrine Therapy in Patients With Rapidly Progressive HR-Positive/HER2-Negative Advanced Breast Cancer

NCT06375707 | Completed Phase 2

• 1 other identifier: HERO-KC23
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Breast Cancer

Keywords

HR positive /HER2 negative; Ribociclib

Outcome Measures

Primary Outcomes (1)

• 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.

  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 (8)

• Progression Free Survival

  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)

  From date of randomization until the date of death from any cause, assessed up to 100 months

• Progression Free Survival2

  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

  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)

  From the date of randomization to the first documented response of either CR or PR, whichever came first, assessed up to 100 months

Study Arms (1)

Ribociclib combined with ET±OFS

EXPERIMENTAL

Drug: Ribociclib

Interventions

Ribociclib DRUG

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.

Also known as: Anastrozole, Letrozole, Exemestane, Fulvestrant, Goserelin

Ribociclib combined with ET±OFS

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Patient is an adult female ≥ 18 years old at the time of informed consent.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patient aged 18 years or older.
• ECOG PS of 0-2.
• Histologically or cytologically confirmed recurrent, metastatic, or unresectable locally advanced breast cancer not amenable to curative surgery or radiotherapy.
• HR-positive/HER2-negative disease: ER expression in at least 10% of tumor-cell nuclei; HER2 IHC 0 or 1+, or IHC 2+ with negative FISH/ISH. When metastatic-tissue pathology is available, the metastatic result is preferred.
• At least one feature of rapid disease progression, as determined by the investigator: symptomatic visceral metastasis; rapidly progressive disease or impending visceral compromise; or markedly symptomatic nonvisceral disease.
• No prior systemic anticancer therapy for recurrent or metastatic disease. Prior neoadjuvant or adjuvant therapy is permitted.
• At least one measurable lesion according to RECIST 1.1.
• Postmenopausal, premenopausal, or perimenopausal status. Premenopausal or perimenopausal patients must agree to receive OFS.
• Adequate baseline organ function: hemoglobin at least 90 g/L; white blood cell count at least 3.5 × 10\^9/L; absolute neutrophil count at least 1.5 × 10\^9/L; platelet count at least 100 × 10\^9/L; serum creatinine not above the institutional ULN; and clinically acceptable hepatic function.
• Negative pregnancy test for patients of childbearing potential and agreement to use effective contraception according to applicable product information and institutional requirements.
• Written informed consent and ability to comply with treatment and follow-up procedures.

You may not qualify if:

• Prior systemic anticancer therapy for recurrent or metastatic disease.
• Prior CDK4/6 inhibitor therapy in the neoadjuvant or adjuvant setting.
• Symptomatic central nervous system metastasis requiring urgent local intervention. Treated, clinically stable, asymptomatic CNS metastasis may be permitted at investigator discretion.
• Known contraindication or serious hypersensitivity to ribociclib or the selected endocrine agent.
• Clinically significant uncontrolled cardiac disease, arrhythmia, congenital long-QT syndrome, uncorrected electrolyte abnormality, or baseline QTcF at or above 450 ms.
• Severe or active cardiovascular, hepatic, respiratory, renal, hematologic, infectious, or psychiatric disease that may increase risk or interfere with efficacy assessment.
• Inability to swallow oral medication or clinically significant gastrointestinal disease that may impair drug absorption.
• Pregnancy or breastfeeding.
• Clinical condition judged by the investigator to preclude safe systemic treatment.
• Any other condition that, in the investigator's opinion, makes participation inappropriate.
• Eligibility for the historical external control cohort
• The external control cohort must satisfy the same core disease, treatment-line, biomarker, rapid-progression, and measurable-disease criteria as the prospective cohort. The following retrospective adaptations are permitted:
• ECOG PS may be taken from an explicit medical-record entry. If functional descriptions are mapped to ECOG PS according to a prespecified rule, the inferred status will be flagged and excluded in sensitivity analyses.
• Rapid disease progression will be determined from contemporaneous symptoms, laboratory findings, imaging descriptions, physician notes, and the treatment-decision context.
• Baseline laboratory values will be the closest available results within the prespecified window before the index chemotherapy date.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead
• Fuyang Cancer Hospital: collaborator
• Affiliated Hospital of Jiangnan University: collaborator
• Jiangyin People's Hospital: collaborator
• Yidu Central Hospital of Weifang: collaborator

Study Sites (1)

Jiangsu Provincial People's Hospital

Nanjing, Jiangsu, 210000, China

Location

MeSH Terms

Interventions

ribociclib; Anastrozole; Letrozole; exemestane; Fulvestrant; Goserelin

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Eligible participants are prospectively enrolled into a single treatment group receiving first-line ribociclib plus endocrine therapy. Comparative outcomes are assessed using a retrospective, non-concurrent external control cohort of patients previously treated with chemotherapy, with or without subsequent endocrine therapy, at the participating institutions.

Study Record Dates

• First Submitted: December 28, 2023
• First Posted: April 19, 2024
• Study Start: January 9, 2024
• Primary Completion: May 30, 2026
• Study Completion: May 30, 2026
• Last Updated: August 5, 2026

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE

Locations

CN (1)