Comparison of Clinical Efficacy Between Letrozole + Ribociclib and Fulvestrant + Letrozole + Ribociclib in Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer

Sponsor
Korea University Guro Hospital
Study ID
NCT05816655
Phase
PHASE2
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
FEMALE
Age
19 Years - 80 Years
Healthy Volunteers
Not accepted

Interventions

Study Details

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.

Key Dates

Start date
May 31, 2023
Status verified
Feb 2025
Primary completion
Dec 31, 2028
Completion
Jun 30, 2029

Study Design

Enrollment
202 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Fulvestrant arm
    fulvestrant + AI + ribociclib
  • Active Comparator: Control arm
    AI + ribociclib

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. ]

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