This open-label, Phase I study will evaluate the impact of severe hepatic impairment on the pharmacokinetics and safety of vemurafenib in participants with BRAF V600 mutation positive cancer. Participants will receive vemurafenib 960 milligrams (mg) (normal hepatic function) or 720 mg (severe hepatic impairment) orally twice daily (BID) on Days 1 to 20 (morning dose) and from Day 27 onward until disease progression or unacceptable toxicity occurs.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
8
Vemurafenib orally BID 960 or 720 mg.
California Cancer Associates for Research & Excellence, Inc.
Encinitas, California, United States
Peninsula and South Eastern Haematology and Oncology Grou
Frankston, Victoria, Australia
District General Hospital of Athens Laiko; 1st Internal Medicine Clinic
Athens, Greece
Dose-Normalized Area Under the Concentration-Time Curve (AUC) of Vemurafenib During the Dose Interval (12 hours) (AUCtau) on Day 20
Time frame: Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours after the morning dose on Day 20
Dose-Normalized Maximum Observed Concentration (Cmax) of Vemurafenib on Day 20
Time frame: Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours after the morning dose on Day 20
Percentage of Participants with Adverse Events (AEs)
Time frame: Baseline up to approximately 3 years
Dose-Normalized AUCtau of of Vemurafenib on Day 1
Time frame: Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose on Day 1
Dose-Normalized AUC from Time 0 to Last Measurable Concentration Time Point (AUC0-last) of Vemurafenib on Day 20
Time frame: Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours after the morning dose on Day 20
Dose-Normalized AUC from Time 0 to Infinity (AUC0-∞) of Vemurafenib on Day 20
Time frame: Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours after the morning dose on Day 20
Dose-Normalized Cmax of Vemurafenib on Day 1
Time frame: Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose on Day 1
Time to Maximum Concentration (tmax) of Vemurafenib on Day 1 and Day 20
Time frame: Day 1: Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose; Day 20: Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours after the morning dose
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Rambam Health Care Campus
Haifa, Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, Israel
SBIH " Clinical Oncological Dispensary # 1"; Chemotherapy department #1 and #2
Krasnodar, Russia
Ege University Medicine Develoment and Pharmacokinetics Research Center; Pulmonary Diseases
Izmir, Turkey (Türkiye)
Velindre Cancer Centre
Cardiff, United Kingdom
Half-life (t1/2) of Vemurafenib in Plasma on Day 20
Time frame: Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours after the morning dose on Day 20
Dose Normalized Apparent Clearance (CL/F) of Vemurafenib on Day 20
Time frame: Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours after the morning dose on Day 20
Trough Plasma Concentration (Cmin or Ctrough) of Vemurafenib
Time frame: Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose on Day 1; Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours after the morning dose on Day 20; Before the morning dose on Days 9 and 15