NCT04657679

Pharmacokinetics and Pharmacogenomics of Ribociclib in Race-based Cohorts

evaLuation of Variations pharmacokinEtics and phArmacogeNOmics of Ribociclib in rAce-based Cohorts: The LEANORA Study

• Status: Terminated
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 21 (actual)
• Sponsor: Georgetown University · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The aim is to determine the pharmacological and biochemical association between ribociclib exposure and CYP3A variants in African American/Blacks and Non-Hispanic White patients. The investigators hypothesize that patients treated with ribociclib who are CYP3A5 poor metabolizers may be exposed to higher levels of ribociclib than CYP3A5 intermediate or normal metabolizers. The findings could allow clinicians to tailor treatments to maintain therapeutic doses while limiting toxicities.

Detailed description

This prospective, multicenter, cohort study will assess ribociclib (600 mg PO daily) pharmacokinetics and pharmacogenomics in female patients with HR+/HER2- metastatic breast cancer. This design will be used for two independent, race-based cohorts: 18 African American/Black patients and 18 Non-Hispanic White patients. Women are eligible if they are older than 18, have HR+/HER2- mBC and are candidates for treatment with a CDK 4/6 inhibitor and endocrine therapy. Patients are ineligible if currently prescribed a medication that inhibits or induces the CYP3A isoenzymes, have baseline electrocardiogram abnormalities, or are otherwise considered to be ineligible for ribociclib. Participants will provide serial blood samples during the first cycle (collected immediately prior to the ribociclib dose, and 0.5hr ± 5min, 1hr ± 5min, 2hr ± 15min, 4hr ± 15min, 6hr ± 15min after the daily dose of ribociclib). Plasma samples will be analyzed via mass spectrometry to characterize the pharmacokinetics (e.g., AUC0-24, Cmax). Pharmacogenetic testing will be performed using the PharmacoScanTM microarray, which tests 4,627 markers in 1,191 genes, including variants in CYP3A4 and CYP3A5.

Conditions

• Breast Cancer

Interventions

Type	Name	Description
DRUG	Ribociclib	Patients will receive ribociclib 600 mg oral (PO) daily for 21 consecutive days of 28-day cycles and endocrine therapy with either letrozole or fulvestrant. Fulvestrant 500 mg intramuscular (IM) will be administered on days 1, 15, 29 of cycle one, and then monthly. Letrozole 2.5 mg oral daily continuously. If premenopausal women have not undergone bilateral salpingo- oophorectomy, they will receive a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., goserelin leuprolide) for ovarian suppression in combination with fulvestrant or letrozole and ribociclib.

Timeline

• Start date: 2021-05-20
• Primary completion: 2023-10-30
• Completion: 2023-10-30
• First posted: 2020-12-08
• Last updated: 2024-11-26
• Results posted: 2024-11-26

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study