Overview

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

Status:
Completed
Trial end date:
2014-04-01
Target enrollment:
0
Participant gender:
All
Summary
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).
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Hoffmann-La Roche
Treatments:
Phenprocoumon
Vemurafenib
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. 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