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

NCT ID: NCT01765543

Last Updated: 2016-12-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2015-11-30

Brief Summary

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).

Conditions

Malignant Melanoma, Neoplasms

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vemurafenib + Rifampin

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).

Group Type: EXPERIMENTAL

Rifampin

Intervention Type: DRUG

Rifampin at a dose of 600 mg as capsules orally once daily will be administered from Days 8 through 23 (Periods B and C).

Vemurafenib

Intervention Type: DRUG

Participants, after an overnight fast of at least 10 hours, will receive vemurafenib at a dose of 960 mg as film-coated tablets orally on Day 1 (Period A) and on Day 17 (Period C).

Interventions

Rifampin

Rifampin at a dose of 600 mg as capsules orally once daily will be administered from Days 8 through 23 (Periods B and C).

Intervention Type: DRUG

Vemurafenib

Participants, after an overnight fast of at least 10 hours, will receive vemurafenib at a dose of 960 mg as film-coated tablets orally on Day 1 (Period A) and on Day 17 (Period C).

Intervention Type: DRUG

Other Intervention Names

RO5185426, Zelboraf

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Rogers, Arkansas, United States

Pleasant Hill, California, United States

Middletown, Ohio, United States

Dallas, Texas, United States

Porto Alegre, Rio Grande do Sul, Brazil

Porto Alegre, Rio Grande do Sul, Brazil

Porto Alegre, Rio Grande do Sul, Brazil

Varaždin, , Croatia

Zagreb, , Croatia

Alexandria, , Egypt

Cairo, , Egypt

Dakahlia, , Egypt

Tanta, , Egypt

Cape Town, , South Africa

Port Elizabeth, , South Africa

Countries

Canada; United States; Brazil; Croatia; Egypt; South Africa

Other Identifiers

2012-003142-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GO28052

Identifier Type: -

Identifier Source: org_study_id