Metastatic Breast CancerPhase 2NCT05816655
Comparison of Clinical Efficacy Between Letrozole + Ribociclib and Fulvestrant + Letrozole + Ribociclib in Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer
A Phase 2 study testing Fulvestrant plus AI plus ribociclib and AI plus ribociclib in people with Metastatic Breast Cancer, run by Korea University Guro Hospital at 2 sites in South Korea.
Trial summary
Aromatase inhibitor (AI) + CDK4/6 inhibitor is settled down as the standard first line therapy for HR+/HER2- metastatic breast cancer and all three CDk4/6 inhibitors, palbociclib, ribociclib, and abemaciclib are currently available for same indications. Read more about this study
- Who is it for?
- Ages 19 to 80 years, women only
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- Fulvestrant plus AI plus ribociclib and AI plus ribociclib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 202 participants
- Where
- 2 sitesSouth Korea
- Study dates
- 31 May 2023to 30 Jun 2029
- 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 to 80 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female ≥ 19 years of age
- Histologically confirmed unresectable, locally advanced or metastatic invasive breast cancer with hormone receptor positive/HER2 negative
- No previous history of systemic endocrine or chemotherapy for metastatic, advanced breast cancer.
- If the patient has received AI as adjuvant endocrine therapy, the treatment free interval (TFI) should be more than 12 months after the end of adjuvant endocrine therapy. If the patient has received tamoxifen for adjuvant endocrine therapy, TFI less than 12 months will be allowed.
- ECOG PS 0-2
- Patients should have measurable or evaluable lesion based on RECIST version 1.1
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- Patients should have adequate organ function:
- ANC (absolute neutrophil count) ≥ 1.5 × 109/L
- Platelet ≥ 100 × 109/L
- Serum Hb ≥ 9.0 g/dL
- INR ≤1.5
- Serum creatinine ≤ 1.5 X ULN
- ALT \& ALT <2.5 X ULN, if patients have hepatic metastasis, ALT \& ALT <5.0 X ULN is allowed
- Total serum bilirubin <1.5 X ULN, if patients have hepatic metastasis, Total serum bilirubin <3.0 X ULN is allowed.
- In the case of childbearing potential, patients who can adhere to appropriate contraception during the study period and for at least 6 months after the end of study treatment.
- Patients who understand the contents of the clinical trial and are cooperative with the process of the clinical trial.
Who cannot join
- Patients with a history of previous treatment with a CDK4/6 inhibitor or other systemic treatment for advanced/metastatic breast cancer
- Patients who have received prior treatment with fulvestrant and any investigational ER-directed therapy including SERDs (selective estrogen receptor degrader)
- Patients who have disease recurrence on aromatase inhibitor treatment as adjuvant endocrine therapy
- Patients who have symptomatic or untreated central nervous system metastasis
- Patients who have a history of cardiovascular disease or heart failure as following conditions; within at least 6 months of myocardial infarction, unstable angina, or uncontrolled arrhythmia.
- Patients having visceral crisis which needs rapid tumor reduction
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- Patients who have a history of any other cancer (except nonmelanoma skin cancer, carcinoma in-situ of the cervix, well-differentiated thyroid cancer)
- Patients unable to cooperate with periodic blood samples collection
- Patients who have active HBV, HCV infection, immune-suppressive disease, or HIV infection. In case of chronic HBV infection, HBV DNA should be negative. Patients with complete remission of HCV infection are allowed.
- Pregnant or breast-feeding women
- Patients who are considered to be unsuitable for this trial by investigators.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
South Korea2 sites, 2 recruiting
- Recruiting
Korea university Guro hospital
Seoul
In Hae Park, MD, +82-2-2626-3172, parkih@korea.ac.kr
- Recruiting
St Mary Hospital
Seoul
Jieun Lee, prof, +82-2-, befamiliar@catholic.ac.kr
About this study
Official title: Comparison of Clinical Efficacy Between Letrozole + Ribociclib and Fulvestrant + Letrozole + Ribociclib in Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer - a Randomized, Phase 2 Study
Aromatase inhibitor (AI) + CDK4/6 inhibitor is settled down as the standard first line therapy for HR+/HER2- metastatic breast cancer and all three CDk4/6 inhibitors, palbociclib, ribociclib, and abemaciclib are currently available for same indications. However, there is no effective treatment strategy for patients who have progressed on AI+CDK4/6 inhibitor. In particular, the clinical efficacies of subsequent hormone therapy are lowered when ESR1 mutations, one of mechanisms of AI resistance occur. In the PADA-1 trial, when ESR1 mutations in ctDNA were detected in patients treated with AI+CDK4/6 inhibitor, AI was switched to fulvestrant even if disease progression was not confirmed clinically. As a result, the median PFS was prolonged by about 8 months in this switching group compared to the group in which AI was continued. The results of this study suggested that delaying the occurrence of ESR1 mutations and early response to them are necessary to increase the effectiveness of hormone therapy.
In SWOG S0226 study, fulvestrant + AI combination showed significant benefits in PFS and OS compared to AI monotherapy as the first line therapy. Based on these results, the NCCN guideline suggests fulvestrant + AI combination as one of the first line hormone therapy options. However, the clinical effect of AI + fulvestrant + CDK4/6 inhibitor has not been investigated yet. Therefore, the investigators are planning to compare the clinical efficacy of AI+ fulvestrant + CDK4/6 inhibitor and AI+CDK4/6 inhibitor, and to investigate if a triple combination regimen can delay the emergence of ESR1 mutations and modulate occurred ESR1 mutations.
- Conditions
- Metastatic Breast Cancer
- Being tested
- Fulvestrant plus AI plus ribociclib, AI plus ribociclib
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fulvestrant plus AI plus ribociclibDrug
Fulvestrant + AI + ribociclib +/- GnRH agonist
AI plus ribociclibDrug
AI + ribociclib +/- GnRH agonist
| Study group | Role | What they receive |
|---|---|---|
| Fulvestrant arm | Experimental | fulvestrant + AI + ribociclib Receives: Drug: Fulvestrant plus AI plus ribociclib |
| Control arm | Active comparator | AI + ribociclib Receives: Drug: AI plus ribociclib |
What is being measured
The primary outcome is the main question the study is designed to answer.
24 month- progression free survival rate
To compare 24 month- progression free survival rate (PFS rate) of letrozole + ribociclib + fulvestrant to letrozole + ribociclib for HR+/HER2- metastatic breast cancer (MBC) as the 1st line endocrine therapy
Measured: the time from randomization until documented disease progression or death from any cause, whichever occurs first, assessed up to 24 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2023
- Study start31 May 2023
- Primary completion31 Dec 2028 (estimated)
- Study completion30 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Breast CancerStudies 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
- 202 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Korea University Guro Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Park, In Hae, Korea University Guro Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05816655
- Sponsor's protocol ID
- KCSG BR22-20
- Status last verified
- Feb 2025
- First submitted
- 22 Mar 2023
- Last updated
- 18 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Clinical Efficacy Between Letrozole + Ribociclib and Fulvestrant + Letrozole + Ribociclib in Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer - a Randomized, Phase 2 Study
- ClinicalTrials.gov ID
- NCT05816655
- Acronym / sponsor ID
- KCSG BR22-20
- Conditions
- Metastatic Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 202 participants (estimated)
- Lead sponsor
- Korea University Guro HospitalUniversity, hospital or other
- Study start
- 31 May 2023 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 30 Jun 2029 (estimated)
- First posted
- 18 Apr 2023 (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.
Aromatase inhibitor (AI) + CDK4/6 inhibitor is settled down as the standard first line therapy for HR+/HER2- metastatic breast cancer and all three CDk4/6 inhibitors, palbociclib, ribociclib, and abemaciclib are currently available for same indications. However, there is no effective treatment strategy for patients who have progressed on AI+CDK4/6 inhibitor. In particular, the clinical efficacies of subsequent hormone therapy are lowered when ESR1 mutations, one of mechanisms of AI resistance occur. In the PADA-1 trial, when ESR1 mutations in ctDNA were detected in patients treated with AI+CDK4/6 inhibitor, AI was switched to fulvestrant even if disease progression was not confirmed clinically. As a result, the median PFS was prolonged by about 8 months in this switching group compared to the group in which AI was continued. The results of this study suggested that delaying the occurrence of ESR1 mutations and early response to them are necessary to increase the effectiveness of hormone therapy.
In SWOG S0226 study, fulvestrant + AI combination showed significant benefits in PFS and OS compared to AI monotherapy as the first line therapy. Based on these results, the NCCN guideline suggests fulvestrant + AI combination as one of the first line hormone therapy options. However, the clinical effect of AI + fulvestrant + CDK4/6 inhibitor has not been investigated yet. Therefore, the investigators are planning to compare the clinical efficacy of AI+ fulvestrant + CDK4/6 inhibitor and AI+CDK4/6 inhibitor, and to investigate if a triple combination regimen can delay the emergence of ESR1 mutations and modulate occurred ESR1 mutations.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fulvestrant arm | Experimental | Drug: Fulvestrant plus AI plus ribociclibfulvestrant + AI + ribociclib |
| Control arm | Active comparator | Drug: AI plus ribociclibAI + ribociclib |
Who may qualify
- Ages
- 19 to 80 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Female ≥ 19 years of age
- Histologically confirmed unresectable, locally advanced or metastatic invasive breast cancer with hormone receptor positive/HER2 negative
- No previous history of systemic endocrine or chemotherapy for metastatic, advanced breast cancer.
- If the patient has received AI as adjuvant endocrine therapy, the treatment free interval (TFI) should be more than 12 months after the end of adjuvant endocrine therapy. If the patient has received tamoxifen for adjuvant endocrine therapy, TFI less than 12 months will be allowed.
- ECOG PS 0-2
Key exclusion criteria (11 listed)
- Patients with a history of previous treatment with a CDK4/6 inhibitor or other systemic treatment for advanced/metastatic breast cancer
- Patients who have received prior treatment with fulvestrant and any investigational ER-directed therapy including SERDs (selective estrogen receptor degrader)
- Patients who have disease recurrence on aromatase inhibitor treatment as adjuvant endocrine therapy
- Patients who have symptomatic or untreated central nervous system metastasis
- Patients who have a history of cardiovascular disease or heart failure as following conditions; within at least 6 months of myocardial infarction, unstable angina, or uncontrolled arrhythmia.
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 |
|---|---|---|
| Fulvestrant plus AI plus ribociclibFulvestrant + AI + ribociclib +/- GnRH agonist | Drug | Fulvestrant arm |
| AI plus ribociclibAI + ribociclib +/- GnRH agonist | Drug | Control arm |
Primary outcome
24 month- progression free survival rate
Time frame: the time from randomization until documented disease progression or death from any cause, whichever occurs first, assessed up to 24 months.
To compare 24 month- progression free survival rate (PFS rate) of letrozole + ribociclib + fulvestrant to letrozole + ribociclib for HR+/HER2- metastatic breast cancer (MBC) as the 1st line endocrine therapy
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 18 Mar 2025.
- Individual participant dataSharing planned: Undecided
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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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fulvestrant plus AI plus ribociclib and AI plus ribociclib in people with Metastatic Breast Cancer, run by Korea University Guro Hospital at 2 sites in South Korea.
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 16 inclusion and 11 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: looking for participants now, as of the sponsor's last update on 18 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
24 month- progression free survival rate (time frame: the time from randomization until documented disease progression or death from any cause, whichever occurs first, assessed up to 24 months.). 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 18 Mar 2025.