OncoMatch/Clinical Trials/NCT05816655
Comparison of Clinical Efficacy Between Letrozole + Ribociclib and Fulvestrant + Letrozole + Ribociclib in Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer
Is NCT05816655 recruiting? Yes, currently enrolling (May 2026). This Phase 2 trial studies multiple treatments including Fulvestrant plus AI plus ribociclib and AI plus ribociclib for metastatic breast cancer.
Treatment: Fulvestrant plus AI plus ribociclib · AI plus ribociclib — 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.
Check if I qualifyExtracted eligibility criteria
Cancer type
Breast Carcinoma
Biomarker criteria
Required: ESR1 hormone receptor positive
hormone receptor positive
Required: HER2 (ERBB2) negative
HER2 negative
Performance status
ECOG 0–2(Ambulatory, capable of self-care)
Prior therapy
Cannot have received: CDK4/6 inhibitor
Patients with a history of previous treatment with a CDK4/6 inhibitor
Cannot have received: systemic therapy
other systemic treatment for advanced/metastatic breast cancer
Cannot have received: endocrine therapy (fulvestrant)
Patients who have received prior treatment with fulvestrant
Cannot have received: investigational ER-directed therapy
any investigational ER-directed therapy including SERDs (selective estrogen receptor degrader)
Cannot have received: aromatase inhibitor
Exception: disease recurrence on aromatase inhibitor treatment as adjuvant endocrine therapy
Patients who have disease recurrence on aromatase inhibitor treatment as adjuvant endocrine therapy
Lab requirements
Blood counts
ANC ≥ 1.5 × 10^9/L; Platelet ≥ 100 × 10^9/L; Serum Hb ≥ 9.0 g/dL; INR ≤1.5
Kidney function
Serum creatinine ≤ 1.5 X ULN
Liver function
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.
Patients should have adequate organ function: ANC (absolute neutrophil count) ≥ 1.5 × 10^9/L; Platelet ≥ 100 × 10^9/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.
Structured fields extracted by AI. May contain errors — verify against the official protocol.
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