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

NCT05816655 | Recruiting Phase 2

• 1 other identifier: KCSG BR22-20
• Study Type: interventional
• Target: 202
• Locations: 1 country
• Sites: 2

Brief 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. 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

Outcome Measures

Primary Outcomes (1)

• 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

  the time from randomization until documented disease progression or death from any cause, whichever occurs first, assessed up to 24 months.

Study Arms (2)

Fulvestrant arm

EXPERIMENTAL

fulvestrant + AI + ribociclib

Drug: Fulvestrant plus AI plus ribociclib

Control arm

ACTIVE COMPARATOR

AI + ribociclib

Drug: AI plus ribociclib

Interventions

Fulvestrant plus AI plus ribociclib DRUG

Fulvestrant + AI + ribociclib +/- GnRH agonist

Fulvestrant arm

AI plus ribociclib DRUG

AI + ribociclib +/- GnRH agonist

Control arm

Eligibility Criteria

• Age: 19 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Korea University Guro Hospital: lead

Study Sites (2)

Korea university Guro hospital

Seoul, South Korea

RECRUITING

St Mary Hospital

Seoul, South Korea

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Fulvestrant; ribociclib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator, Clinical professor

Study Record Dates

• First Submitted: March 22, 2023
• First Posted: April 18, 2023
• Study Start: May 31, 2023
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: March 18, 2025

Record last verified: 2025-02

Locations

KR (2)