A PHASE I, OPEN-LABEL, MULTICENTER, RANDOMINZED, PARALELL STUDY TO INVESTIGATE THE EFFECT OF VEMURAFENIB ON THE PHARMACOKINETICS OF A SINGLE ORAL DOSE OF PHENPROCOUMON IN PATIENTS WITH BRAFV600 MUTATION-POSITIVE METASTATIC MALIGNANCY
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