A Study to Investigate the Effect of Itraconazole and Rifampin on Pharmacokinetics (PK) of Vemurafenib at Steady State
- Conditions
- Metastatic Melanoma, BRAF V600 Mutation Positive
- Interventions
- Registration Number
- NCT02608034
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
This is a two-part, Phase 1, open-label, multicenter, two-period, one-sequence study to investigate the effect of itraconazole and rifampin on the PK of vemurafenib following multiple 960 milligrams (mg) twice daily (BID) dosing in adult participants with unresectable Stage IIIC or Stage IV metastatic melanoma positive for the BRAF V600 mutation, or other malignant tumor types that harbor a V600-activating mutation of BRAF where the participant has no acceptable standard treatment options.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 32
- Participants with age greater than or equal to (>=) 18 years with either unresectable Stage IIIC or Stage IV metastatic melanoma positive for the BRAF V600 mutation, or other malignant tumor types that harbor a V600-activating mutation of BRAF
- Eastern Cooperative Oncology Group Performance Status 0 to 2
- Life expectancy >=12 weeks
- Adequate hematologic and end organ function obtained within 2 weeks prior to first dose of study drug
- Female participants of childbearing potential and male participants with partners of childbearing potential must agree to always use two effective methods of contraception including at least one method with a failure rate of <1% per year during the course of the study and for at least 6 months after completion of study treatment
- Negative serum pregnancy test within 7 days prior to commencement of dosing in women of childbearing potential
- Absence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- Prior treatment with vemurafenib or other BRAF inhibitor within 42 days of Study Day 1 of Period A
- Allergy or hypersensitivity to components of the vemurafenib formulation
- Experimental therapy within 4 weeks prior to first dose of study drug treatment on Study Day 1 of Period A
- Major surgical procedure or significant traumatic injury within 14 days prior to first dose of study drug treatment on Study Day 1 of Period A, or anticipation of the need for major surgery during study treatment
- Prior anti-cancer therapy (e.g., biologic or other targeted therapy, chemotherapy) within 28 days (6 weeks for nitrosoureas or mitomycin C, and 14 days for hormonal therapy or kinase inhibitors) before the first dose of study treatment on Study Day 1 of Period A.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Part 1: Vemurafenib+Itraconazole Itraconazole Part 1: Participants will receive vemurafenib orally BID up to Day 20 (Period A) followed by vemurafenib orally BID along with itraconazole orally once in the morning from Days 21 to 40 (Period B).\\nPart 2: Participants will receive vemurafenib orally BID up to Day 20 (Period A) followed by vemurafenib orally BID along with rifampin orally once in the morning from Days 21 to 40 (Period B). Part 1: Vemurafenib+Itraconazole Rifampin Part 1: Participants will receive vemurafenib orally BID up to Day 20 (Period A) followed by vemurafenib orally BID along with itraconazole orally once in the morning from Days 21 to 40 (Period B).\\nPart 2: Participants will receive vemurafenib orally BID up to Day 20 (Period A) followed by vemurafenib orally BID along with rifampin orally once in the morning from Days 21 to 40 (Period B). Part 1: Vemurafenib+Itraconazole Vemurafenib Part 1: Participants will receive vemurafenib orally BID up to Day 20 (Period A) followed by vemurafenib orally BID along with itraconazole orally once in the morning from Days 21 to 40 (Period B).\\nPart 2: Participants will receive vemurafenib orally BID up to Day 20 (Period A) followed by vemurafenib orally BID along with rifampin orally once in the morning from Days 21 to 40 (Period B).
- Primary Outcome Measures
Name Time Method Area under the concentration-time curve From Time 0 to 12 Hours Postdose (AUC0-12) Period A and B: Pre-morning dose on Day 18, 19, and 20 and 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose on Day 20 Maximum observed concentration (Cmax) Period A and B: Pre-morning dose on Day 18, 19, and 20 and 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose on Day 20 Time to maximum concentration (Tmax) Period A and B: Pre-morning dose on Day 18, 19, and 20 and 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose on Day 20
- Secondary Outcome Measures
Name Time Method Incidence of adverse events 28 days after last dose of study treatment (last dose = Day 40)
Trial Locations
- Locations (11)
Hadassah Ein Karem Hospital; Oncology Dept
🇮🇱Jerusalem, Israel
Samsung Medical Center; Gastroenterology
🇰🇷Seoul, Korea, Republic of
FSBSI "N. N. Blokhin Russian Cancer Research Center"
🇷🇺Moscow, Russian Federation
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Rambam Health Care Campus; Oncology
🇮🇱Haifa, Israel
Mary Crowley Medical Research Center
🇺🇸Dallas, Texas, United States
Tel Aviv Sourasky Medical Center; Pharmacy
🇮🇱Tel Aviv, Israel
Severance Hospital - Yonsei Uni ; Obstetrics & Gynaecology Dept.
🇰🇷Seoul, Korea, Republic of
Asan Medical Center; Division of Oncology
🇰🇷Seoul, Korea, Republic of
Republican Clinical Oncologic Dispensary of Republic Of Tatarstan
🇷🇺Kazan, Russian Federation
St. Petersburg Oncology Hospital
🇷🇺St Petersburg, Russian Federation