A Study of the Effect of Vemurafenib on the Pharmacokinetics of Acenocoumarol in Patients With BRAFV600 Mutation-Positive Metastatic Malignancy

NCT ID: NCT01851824

Last Updated: 2016-11-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2014-06-30

Brief Summary

This open-label, multicenter, 3-period, fixed-sequence study will evaluate the effect of multiple doses of vemurafenib on the pharmacokinetics of a single dose of acenocoumarol in participants with BRAFV600 mutation-positive metastatic malignancies. Participants will receive a single dose of acenocoumarol 4 mg orally on Day 1 and Day 23, vemurafenib 960 mg orally twice daily on Days 4-26. After completion of pharmacokinetic assessments on Day 26, 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
• Blinding Strategy: NONE

Study Groups

Acenocoumarol + Vemurafenib

Group Type: EXPERIMENTAL

acenocoumarol

Intervention Type: DRUG

4 mg single oral doses on Days 1 and 23

vemurafenib

Intervention Type: DRUG

960 mg orally bid, 20 days (Days 4-23)

Interventions

acenocoumarol

4 mg single oral doses on Days 1 and 23

Intervention Type: DRUG

vemurafenib

960 mg orally bid, 20 days (Days 4-23)

Intervention Type: DRUG

Other Intervention Names

Zelboraf

Eligibility Criteria

Inclusion Criteria

• Adult patients, 18-70 years of age
• Patients with either unresectable Stage IIIc or IV BRAFV600 mutation-positive metastatic melanoma or other malignant BRAFV600 mutation-positive tumor type and who have no acceptable standard treatment options
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
• Full recovery from any major surgery or significant traumatic injury at least 14 days prior to the first dose of study treatment
• Adequate hematologic and end organ function
• Female patients of childbearing potential and male patients with female partners of childbearing potential must agree to use 2 effective methods of contraception as defined by protocol during the course of the study and for at least 6 months after completion of study treatment

Exclusion Criteria

• Prior treatment with vemurafenib or other BRAF inhibitor within 42 days of Day 1
• Prior anti-cancer therapy within 28 days (6 weeks for nitrosureas or mitocyn C, or 14 days for hormonal therapy or kinase inhibitors) before the first dose of study treatment Day 1
• Palliative radiotherapy within 2 weeks prior to first dose of study treatment Day 1
• Experimental therapy within 4 weeks prior to first dose of study treatment Day 1
• History of clinically significant cardiac or pulmonary dysfunction, including current uncontrolled Grade >/=2 hypertension or unstable angina
• Current Grade >/=2 dyspnea or hypoxia or need for oxygen supplementation
• History of myocardial infarction within 6 months prior to first dose of study treatment
• Active central nervous system lesions (i.e. participants with radiographically unstable, symptomatic lesions)
• History of bleeding or coagulation disorders
• Allergy or hypersensitivity to vemurafenib or acenocoumarol formulations
• History of malabsorption or other condition that would interfere with the enteral absorption of study treatment
• Participants with VKORC1 mutations (1639G→A, 1173C→T) in either one allele (heterozygous)or two alleles (homozygous)
• Participants with CYP2C9*3 mutations in either one allele (heterozygous) or two alleles (homozygous)
• History of clinically significant liver disease (including cirrhosis), current alcohol abuse, or active hepatitis B or hepatitis C virus infection
• Human immunodeficiency virus (HIV) infection requiring antiretroviral treatment, or AIDS-related illness
• Pregnant or lactating 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

Wodonga, New South Wales, Australia

Buxtehude, , Germany

Essen, , Germany

Mannheim, , Germany

Crete, , Greece

Thessaloniki, , Greece

Budapest, , Hungary

Amsterdam, , Netherlands

Maastricht, , Netherlands

Utrecht, , Netherlands

Auckland, , New Zealand

Christchurch, , New Zealand

Lisbon, , Portugal

Porto, , Portugal

Belgrade, , Serbia

Barcelona, Barcelona, Spain

Barcelona, Barcelona, Spain

Madrid, Madrid, Spain

Madrid, Madrid, Spain

Madrid, Madrid, Spain

Countries

Australia; Germany; Greece; Hungary; Netherlands; New Zealand; Portugal; Serbia; Spain

Other Identifiers

2012-003706-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GO28397

Identifier Type: -

Identifier Source: org_study_id