Clinical trial NCT02608034: A Study to Investigate the Effect of Itraconazole and Rifampin on Pharmacokinetics (PK) of Vemurafenib at Steady State
Official title: A Two-part, Phase I, Open-label, Multicenter, Two-period, One-sequence Study to Investigate the Effect of Itraconazole and Rifampin on the PK of Vemurafenib at Steady State
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Melanoma, BRAF V600 Mutation Positive
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2015-11-18
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Area under the concentration-time curve From Time 0 to 12 Hours Postdose (AUC0-12)
timeFrame: 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
measure: Maximum observed concentration (Cmax)
timeFrame: 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
measure: Time to maximum concentration (Tmax)
timeFrame: 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 outcomes:
measure: Incidence of adverse events
timeFrame: 28 days after last dose of study treatment (last dose = Day 40)
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Mary Crowley Medical Research Center
state: Texas
city: Haifa
country: Israel
facility: Rambam Health Care Campus; Oncology
city: Jerusalem
country: Israel
facility: Hadassah Ein Karem Hospital; Oncology Dept
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center; Pharmacy
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center; Gastroenterology
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center; Division of Oncology
city: Seoul
country: Korea, Republic of
facility: Severance Hospital - Yonsei Uni ; Obstetrics & Gynaecology Dept.
city: Kazan
country: Russian Federation
facility: Republican Clinical Oncologic Dispensary of Republic Of Tatarstan
city: Moscow
country: Russian Federation
facility: FSBSI "N. N. Blokhin Russian Cancer Research Center"
city: St Petersburg
country: Russian Federation
facility: St. Petersburg Oncology Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: