A Study on the Effect of Vemurafenib on the Pharmacokinetics of a Single Dose of Tizanidine in Patients With BRAFV600 Mutation-Positive Metastatic Malignancies

NCT ID: NCT01844674

Last Updated: 2017-03-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-02
• Study Completion Date: 2014-08-26

Brief Summary

This open-label, multicenter, 3-period, fixed-sequence study will evaluate the effect of multiple oral doses of vemurafenib on the pharmacokinetics of a single oral dose of tizanidine in participants with BRAFV600 mutation-positive metastatic malignancies. Participants will receive a single oral dose of tizanidine on Day 1, vemurafenib orally twice daily on Days 2 to 21, and tizanidine and vemurafenib on Day 22. Eligible participants will have the option to continue treatment with vemurafenib as part of an extension study (NCT01739764).

Conditions

Malignant Melanoma, Neoplasms

Study Design

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

Study Groups

Pharmacokinetic Population

All participants will receive a 3-period treatment including single-dose tizanidine on Day 1, twice-daily vemurafenib on Days 2 to 21, and both agents together on Day 22.

Group Type: EXPERIMENTAL

Tizanidine

Intervention Type: DRUG

Participants will receive tizanidine as single oral doses, 2 milligrams (mg) on Day 1 and repeated on Day 22, each following an overnight fast \>/= 10 hours.

Vemurafenib

Intervention Type: DRUG

Participants will receive vemurafenib as multiple oral doses, 960 mg twice daily on Days 2 to 22.

Interventions

Tizanidine

Participants will receive tizanidine as single oral doses, 2 milligrams (mg) on Day 1 and repeated on Day 22, each following an overnight fast \>/= 10 hours.

Intervention Type: DRUG

Vemurafenib

Participants will receive vemurafenib as multiple oral doses, 960 mg twice daily on Days 2 to 22.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Adults 18 to 70 years of age, inclusive
• Unresectable Stage IIIc or IV metastatic melanoma positive for the BRAFV600 mutation or other malignant tumor type which harbors a V600 activating mutation of BRAF, as determined by Cobas 4800 BRAFV600 Mutation Test or a DNA sequencing method
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
• Life expectancy greater than or equal to (>/=) 12 weeks
• Participant has not consumed tobacco or nicotine-containing products for 42 days prior to first dose of study drug, and must agree to refrain from such products while on study
• Adequate hematologic, renal and liver function

Exclusion Criteria

• Prior treatment with vemurafenib or other BRAF inhibitor within 42 days of Day 1
• History of or current clinically significant cardiac or pulmonary dysfunction, including current uncontrolled Grade >/= 2 hypertension or unstable angina
• Current dyspnea at rest due to complications of advanced malignancy or any requirement for supplemental oxygen
• Active central nervous system lesions (participants with radiographically unstable, symptomatic lesions)
• Participants with CYP1A2 gene mutation (-3113G->A), either in one or two alleles
• Allergy or hypersensitivity to vemurafenib or tizanidine formulations
• Current severe uncontrolled systemic disease
• Inability or unwillingness to swallow pills
• History of malabsorption or other condition that would interfere with enteral absorption of study treatment
• History of clinically significant liver disease (including cirrhosis), current alcohol abuse, or human immunodeficiency (HIV) infection requiring antiretroviral treatment, acquired immune deficiency syndrome (AIDS)-related illness, or active hepatitis B or C
• Pregnant or breastfeeding women

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 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

Diablo Valley Oncology and Hematology

Pleasant Hill, California, United States

Karmanos Cancer Center

Detroit, Michigan, United States

Duke University Health Systems

Durham, North Carolina, United States

Instituto Nacional do Cancer - INCA

Rio de Janeiro, Rio de Janeiro, Brazil

Hospital de Caridade de Ijui; Oncologia

Ijuí, Rio Grande do Sul, Brazil

CITO - Centro Integrado de Terapia Onco-Hematológica - Hospital da Cidade de Passo Fundo

Passo Fundo, Rio Grande do Sul, Brazil

Hospital Sao Lucas - PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

CSSS champlain - Charles-Le Moyne

Greenfield Park, Quebec, Canada

Bank of Cyprus Oncology Center

Nicosia, , Cyprus

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Asan Medical Center.

Seoul, , South Korea

Countries

United States; Brazil; Canada; Cyprus; South Korea

Other Identifiers

2012-003705-94

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GO28396

Identifier Type: -

Identifier Source: org_study_id