Fulvestrant With Ribociclib Versus Physician's Choice Treatments Recurred After Completion of Adjuvant Cyclin-Dependent Kinase 4/6 Inhibitors in HR+, HER2- Metastatic Breast Cancer

NCT06849947 | Not Yet Recruiting Phase 2

• 1 other identifier: 2025-02-104
• Study Type: interventional
• Target: 272
• Locations: 0 countries
• Sites: N/A

Brief Summary

▪ Fulvestrant With Ribociclib versus Physician's choice treatments for the patients who recurred after completion of Adjuvant Cyclin-Dependent Kinase 4/6 Inhibitors in HR+, HER2- Metastatic Breast Cancer as first line treatment

Conditions

Breast Cancer Metastatic

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  From the time from randomization to first documented progression or death, whichever occurs first

  Up to 5 years

Secondary Outcomes (3)

• Overall survival

  Up to 5 years

• Objective Response Rate

  Up to 5 years

• Adverse Events

  Up to 5 years

Study Arms (2)

Ribociclib group

EXPERIMENTAL

▪ Ribociclib group \- Ribociclib (600 mg orally once daily on days 1 to 21 in a 28 day cycle) + Fulvestrant (500mg intramuscular injection on day 1 in a 28 day cycle and day 15 of Cycle 1) ± Leuprorelin (3.75 mg subcutaneously every 28 days in premenopausal or perimenopausal women)

Drug: Ribociclib with fulvestrant

Physician's choice treatments group

ACTIVE COMPARATOR

▪ Fulvestrant or exemestane group 1. Fulvestrant (500mg intramuscular injection on day 1 in a 28 day cycle and day15 of Cycle 1) ± Leuprorelin (3.75 mg subcutaneously every 28 days in premenopausal or periomenopausal women) OR, 2. Exemestane (25 mg orally once daily on day 1 to 28 in a 28 day cycle) + Everolimus (10 mg orally once daily on day 1 to 28 in a 28 day cycle) ± Leuprorelin (3.75 mg subcutaneously every 28 days in premenopausal or perimenopausal women)

Drug: Physician's choice treatments group

Interventions

Ribociclib with fulvestrant DRUG

▪ Ribociclib group \- Ribociclib (600 mg orally once daily on days 1 to 21 in a 28 day cycle) + Fulvestrant (500mg intramuscular injection on day 1 in a 28 day cycle and day 15 of Cycle 1) ± Leuprorelin (3.75 mg subcutaneously every 28 days in premenopausal or perimenopausal women)

Ribociclib group

Physician's choice treatments group DRUG

▪Fulvestrant or exemestane group 1. Fulvestrant (500mg intramuscular injection on day 1 in a 28 day cycle and day15 of Cycle 1) ± Leuprorelin (3.75 mg subcutaneously every 28 days in premenopausal or periomenopausal women) OR, 2. Exemestane (25 mg orally once daily on day 1 to 28 in a 28 day cycle) + Everolimus (10 mg orally once daily on day 1 to 28 in a 28 day cycle) ± Leuprorelin (3.75 mg subcutaneously every 28 days in premenopausal or perimenopausal women)

Physician's choice treatments group

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must be at least 19 years of age at the time of signing the informed consent.
• Patient has advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy.
• Patient has HR-positive/HER2-negative invasive breast cancer (based on most recently analyzed biopsy)
• HER2 status 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 (FISH, CISH, or SISH) test is required by local laboratory testing, according to ASCO/CAP guidelines for HER2 testing (Wolff et al. 2018).
• HR status is defined as positive in ER expression by IHC, according to the relevant ASCO/CAP Guidelines (Allison et al. 2020)
• Patient must have received either at least 1 year of adjuvant abemaciclib or ribociclib.
• Recurrence of advanced breast cancer was diagnosed ≥1 year from the last dose of adjuvant CDK4/6 inhibitor.
• Patients must have received a minimum of 2 years of adjuvant endocrine therapy (either alone or in combination with CDK4/6 inhibitors)
• Patient has an ECOG PS 0 or 1.
• Must have at least one measurable lesion according to RECIST v1.1. Patients without measurable lesions must have at least one lytic bone lesion.
• Patient has adequate bone marrow and organ function as defined by the following laboratory values:
• Absolute neutrophil count ≥ 1.5 × 109/L
• Platelets ≥ 100 × 109/L
• Hemoglobin ≥ 9.0 g/dL
• Serum creatinine \< 1.5 mg/dL or CCr ≥ 50 mL/day

You may not qualify if:

• Patients whose cancer recurs one year or later after completing adjuvant endocrine therapy
• Patients who have been free from endocrine therapy for at least 2 years
• Patient whose disease recurred during or within 1 year from adjuvant CDK4/6 inhibitor treatment.
• Patient who did receive adjuvant palbociclib irrespective of disease-free interval.
• Patients who did not receive adjuvant CDK4/6 inhibitor treatment or who received less than 1 year of adjuvant CDK4/6 inhibitor treatment.
• Patients who have received fulvestrant in adjuvant setting before randomization.
• Patients who have received any line of systemic treatment for advanced breast cancer is not eligible.
• Participant has not recovered from clinical, and laboratory acute toxicities related to prior anticancer therapies to NCI CTCAE version 4.03 Grade ≤1. Exception to this criterion: participants with grade 2 taxane-induced neuropathy, any grade of alopecia, amenorrhea or other toxicities not considered a safety risk for the participant as per investigator's discretion, are allowed to enter the study.
• Patient has a concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated basal cell carcinoma, squamous cell skin carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
• Patient with symptomatic, unstable CNS metastases. Note: Symptomatic CNS metastases should be locally treated prior enrollment.
• Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
• Patient has a known history of HIV infection (testing not mandatory).
• Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, contraindicate patient participation in the clinical study (e.g., chronic pancreatitis, chronic active hepatitis, etc.).
• Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including but not limited to any of the following:
• History of documented myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to study entry

Sponsors & Collaborators

• Yeon Hee Park: lead

MeSH Terms

Interventions

ribociclib; Fulvestrant

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Central Study Contacts

Yeon Hee Park, Ph.D

CONTACT

0234103459; yhparkhmo@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 23, 2025
• First Posted: February 27, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): June 30, 2031
• Study Completion (Estimated): December 31, 2031
• Last Updated: December 24, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share