Metastatic Melanoma, BRAF V600 Mutation Positive
Conditions
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.
Interventions
DRUGItraconazole
Itraconazole will be administered as a 200 mg oral solution QD during Part 1 only for 20 consecutive days.
DRUGRifampin
Rifampin will be administered as a 600 mg oral solution QD during Part 2 only for 20 consecutive days.
DRUGVemurafenib
Vemurafenib will be administered in both Part 1 and Part 2 at a dose of 960 mg BID for at least 40 conseutive days.
Sponsors
Genentech, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| Incidence of adverse events | 28 days after last dose of study treatment (last dose = Day 40) |
Countries
Israel, Russia, South Korea, United States
Outcome results
None listed