A Pharmacokinetics (PK) Study to Investigate the Effect of Rifampin on PK of Vemurafenib (Zelboraf)

Roche

Status and phase: Completed; Phase 1

Conditions: Malignant Melanoma, Neoplasms

Treatments: Drug: Vemurafenib; Drug: Rifampin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01765543

GO28052

2012-003142-33 (EudraCT Number)

Details and patient eligibility

About

This open-label, multi-center, three-period, one-sequence study will investigate the effect of rifampin on the PK of vemurafenib in participants with unresectable BRAFV600-mutation positive metastatic melanoma or other malignant tumor type that harbors a V600-activating mutation of BRAF without acceptable standard treatment options. Eligible participants will have the option to continue treatment with vemurafenib as part of an extension study GO28399 (NCT01739764).

Enrollment: 27 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants with either unresectable Stage IIIc or Stage IV metastatic melanoma positive for the BRAF V600 mutation or other malignant tumor type that harbors a V600-activating mutation of BRAF, as determined by results of cobas® 4800 BRAF V600 mutation test or a Deoxyribonucleic acid (DNA) sequencing method, and who have no acceptable standard treatment options
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
• Life expectancy of greater than or equal to (>/=) 12 weeks
• Full recovery from the effects of any major surgery or significant traumatic injury within 14 days prior to the first dose of study treatment
• Adequate hematologic and end organ function
• Female participants of childbearing potential and male participants with partners of childbearing potential must agree to always use 2 effective methods of contraception
• Negative serum pregnancy test within 7 days prior to commencement of dosing in women of childbearing potential

Exclusion criteria

• Prior treatment with vemurafenib or other BRAF inhibitor within 42 days of first dose of study drug
• Requirement for immediate or urgent treatment with daily vemurafenib and for whom the intermittent schedule of vemurafenib employed during the 24-day period for this trial is not clinically acceptable
• Allergy or hypersensitivity to components of the vemurafenib formulation
• Experimental therapy within 4 weeks prior to first dose of study drug
• Major surgical procedure or significant traumatic injury within 14 days prior to first dose of study drug, or anticipation of the need for major surgery during study treatment
• Prior anti-cancer therapy within 28 days before the first dose of study drug
• History of clinically significant cardiac or pulmonary dysfunction
• History of symptomatic congestive heart failure of any New York Heart Association class or serious cardiac arrhythmia requiring treatment
• History of myocardial infarction within 6 months prior to first dose of study drug
• Current dyspnea at rest, owing to complications of advanced malignancy or any requirement for supplemental oxygen to perform activities of daily living
• History of congenital long QT syndrome or corrected QT interval (QTc) greater than (>) 450 milliseconds
• Active central nervous system lesions
• Uncontrolled or poorly controlled diabetes
• Current severe, uncontrolled systemic disease

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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27 participants in 1 patient group

Vemurafenib + Rifampin

Experimental group

Description:

There will be 3 intervention periods in the study: Period A (Days 1 to 7), Period B (Days 8 to 16), and Period C (Days 17 to 24). Participants, after an overnight fast of at least 10 hours, will receive vemurafenib at a dose of 960 milligrams (mg) as film-coated tablets orally alone on Day 1 (Period A); with rifampin (at a dose of 600 mg as capsules orally) on Day 17 (Period C); and rifampin alone at a dose of 600 mg as capsules orally once daily will be administered from Days 8 through 16 (Period B) and from Days 18 through 23 (Period C).

Treatment:

Drug: Rifampin

Drug: Vemurafenib