Actively Recruiting
Comparison of Clinical Efficacy Between Letrozole + Ribociclib and Fulvestrant + Letrozole + Ribociclib in Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer
Led by Korea University Guro Hospital · Updated on 2025-03-18
202
Participants Needed
2
Research Sites
317 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
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
Official Title
Comparison of Clinical Efficacy Between Letrozole + Ribociclib and Fulvestrant + Letrozole + Ribociclib in Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Female aged 19 years or older
- Histologically confirmed unresectable, locally advanced or metastatic invasive breast cancer with hormone receptor positive/HER2 negative
- No previous systemic endocrine or chemotherapy for metastatic, advanced breast cancer
- Treatment free interval more than 12 months after adjuvant AI therapy; TFI less than 12 months allowed if tamoxifen was used
- ECOG performance status 0 to 2
- Measurable or evaluable lesion based on RECIST version 1.1
- Adequate organ function including ANC 1.5 10^9/L, platelets 100 10^9/L, hemoglobin 9.0 g/dL, INR 1.5, creatinine 1.5 times ULN, ALT less than 2.5 times ULN (or less than 5.0 times ULN if hepatic metastasis), total bilirubin less than 1.5 times ULN (or less than 3.0 times ULN if hepatic metastasis)
- Use of appropriate contraception in patients of childbearing potential during the study and for 6 months after treatment
- Ability to understand and cooperate with the clinical trial process
You will not qualify if you...
- Prior treatment with CDK4/6 inhibitors or systemic therapy for advanced/metastatic breast cancer
- Previous treatment with fulvestrant or investigational ER-directed therapies including SERDs
- Recurrence during aromatase inhibitor adjuvant therapy
- Symptomatic or untreated central nervous system metastases
- Recent history (within 6 months) of serious cardiovascular events such as myocardial infarction, unstable angina, or uncontrolled arrhythmia
- Presence of visceral crisis requiring rapid tumor reduction
- History of other cancers except certain nonmelanoma skin cancers, cervical carcinoma in situ, or well-differentiated thyroid cancer
- Inability to cooperate with periodic blood sample collection
- Active hepatitis B, hepatitis C (unless in complete remission), immunosuppressive disease, or HIV infection
- Pregnant or breastfeeding women
- Deemed unsuitable for the trial by investigators
AI-Screening
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Trial Site Locations
Total: 2 locations
1
Korea university Guro hospital
Seoul, South Korea
Actively Recruiting
2
St Mary Hospital
Seoul, South Korea
Actively Recruiting
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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