Breast Cancer MetastaticPhase 2NCT06849947
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
A Phase 2 study testing Ribociclib with fulvestrant and Physician's choice treatments group in people with Breast Cancer Metastatic, run by Yeon Hee Park.
Trial 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 Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Breast Cancer Metastatic
- What is being tested?
- Ribociclib with fulvestrant and Physician's choice treatments group
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 272 participants
- Where
- No sites listed yet
- Study dates
- 1 Feb 2026to 31 Dec 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
- In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) should be below 2.5 × upper limit of normal(ULN). If the patient has liver metastases, ALT and AST should be < 5 × ULN
- Total serum bilirubin < ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin <1.5 x ULN of the local laboratory in patients with well documented Gilbert's Syndrome
- Patient must be able to swallow study therapy
- Patient must be able to communicate with the investigator and comply with the requirements of the study procedures
- Patient must be willing to remain at the clinical site as required by the protocol.
Who cannot join
- 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.
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- 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
- Documented cardiomyopathy
- Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: ① Risk factors for Torsades de Pointe (TdP) including uncorrected hypocalcemia, hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia ② Concomitant medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued or replaced by safe alternative medication (e.g., within 5 half-lives or 7 days prior to starting study drug) ③ Inability to determine the QTcF interval
- Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third-degree AV block)
- Patient is currently receiving any of the following substances and cannot be discontinued 7 days prior to Cycle 1 Day 1:
- Concomitant medications, herbal supplements, and/or fruits (e.g., grapefruit, pummelos, star fruit, Seville oranges) and their juices that are strong inducers or inhibitors of CYP3A4/5
- Medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5.
- Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects of surgery.
- Patient who has received any investigational drug(s) within 14 days prior to first day treatment or within 5 half-lives of the investigational product (whichever is longer).
- Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment.
- Note: The following uses of corticosteroids are permitted: single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular).
- Patient is concurrently using other antineoplastic agents (except for adjuvant endocrine treatment monotherapy)
- Patient who has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to randomization, and who has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia) and/or if ≥ 25% of the bone marrow was irradiated.
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of study treatment and after stopping study medication.* Highly effective contraception methods include:
- Ribociclib : For at least 3 weeks after the last dose, Fulvestrant : For 2 years after the last dose, Everolimus : For up to 8 weeks after the last dose.
- Effective contraception must be used as follows.
- Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
- Total hysterectomy (surgical removal of the uterus and cervix) or tubal ligation (getting your "tubes tied") at least six weeks before taking study treatment.
- Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject.
- Combination of the following: Barrier methods of contraception: Condom and intrauterine devices (IUDs) (e.g., loop insertion)
- Not able to understand and to comply with study instructions and requirements.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Randomized Phase II Trial of 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 (CLEE011AKR06R)
▪ 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
Read the detailed description
- Treatment Arm : 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) OR,
- Control Arm (Physician's choice treatments)
- 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,
- 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)
- Conditions
- Breast Cancer Metastatic
- Being tested
- Ribociclib with fulvestrant, Physician's choice treatments group
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ribociclib with fulvestrantDrug
▪ 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)
Physician's choice treatments groupDrug
▪Fulvestrant or exemestane group
- 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,
- 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)
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: Drug: Physician's choice treatments group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival
From the time from randomization to first documented progression or death, whichever occurs first
Measured: Up to 5 years
Secondary outcomes (3)
Overall survival
From date of randomization to date of death due to any cause.
Measured: Up to 5 years
Objective Response Rate
Assessed by RECIST 1.1. Cinical benefit rate defined as percentage of patients with CR, PR per RECIST 1.1 or SD lasting 24 weeks or longer
Measured: Up to 5 years
Adverse Events
Incidence/severity of adverse events, lab abnormalities based on CTCAE4.03
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2025
- Study start1 Feb 2026 (estimated)
- Primary completion30 Jun 2031 (estimated)
- Study completion31 Dec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast Cancer MetastaticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 272 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yeon Hee Park
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Yeon Hee Park, Samsung Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06849947
- Sponsor's protocol ID
- 2025-02-104
- Status last verified
- Dec 2025
- First submitted
- 23 Feb 2025
- Last updated
- 24 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase II Trial of 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 (CLEE011AKR06R)
- ClinicalTrials.gov ID
- NCT06849947
- Acronym / sponsor ID
- 2025-02-104
- Conditions
- Breast Cancer Metastatic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 272 participants (estimated)
- Lead sponsor
- Yeon Hee ParkUniversity, hospital or other
- Study start
- 1 Feb 2026 (estimated)
- Primary completion
- 30 Jun 2031 (estimated)
- Study completion
- 31 Dec 2031 (estimated)
- First posted
- 27 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
▪ 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
Detailed description
- Treatment Arm : 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) OR,
- Control Arm (Physician's choice treatments)
- 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,
- 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)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ribociclib group | Experimental | Drug: Ribociclib with fulvestrant▪ 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) |
| Physician's choice treatments group | Active comparator | Drug: Physician's choice treatments group▪ 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) |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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)
- 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.
Key exclusion criteria (36 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ribociclib with fulvestrant▪ 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 group |
| Physician's choice treatments group▪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 |
Primary outcome
Progression Free Survival
Time frame: Up to 5 years
From the time from randomization to first documented progression or death, whichever occurs first
3 secondary outcomes
Overall survival
Time frame: Up to 5 years
Objective Response Rate
Time frame: Up to 5 years
Adverse Events
Time frame: Up to 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ribociclib with fulvestrant and Physician's choice treatments group in people with Breast Cancer Metastatic, run by Yeon Hee Park.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 24 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yeon Hee Park, Ph.D (0234103459, yhparkhmo@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (time frame: Up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Dec 2025.