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

Roche

Status and phase

Completed

Phase 1

Conditions

Malignant Melanoma, Neoplasms

Treatments

Drug: vemurafenib

Drug: phenprocoumon

Study type

Interventional

Funder types

Industry

Identifiers

NCT01849666

2012-003707-35 (EudraCT Number)

GO28398

Details and patient eligibility

About

This open-label, multicenter, parallel study will evaluate the effect of multiple doses of vemurafenib on the pharmacokinetics of a single dose of phenprocoumon in patients with BRAFV600 mutation-positive metastatic malignancies. Patients will be randomized to receive either treatment A: a single oral dose of phenprocoumon 6 mg on Day 1 (Eligible patients will have the option to continue treatment with vemurafenib as part of an extension study (NCT01739764).), or treatment B: vemurafenib 960 mg orally twice daily on Days 1-29 plus a single oral dose of phenprocoumon 6 mg on Day 22 (with the option to receive vemurafenib in the extension study after completion of pharmacokinetic assessments).

Enrollment

2 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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. patients with radiographically unstable, symptomatic lesions)
History of bleeding or coagulation disorders
Allergy or hypersensitivity to vemurafenib or phenprocoumon formulations
History of malabsorption or other condition that would interfere with the enteral absorption of study treatment
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