A Study of the Effect of Vemurafenib on the Pharmacokinetics of Phenprocoumon in Patients With BRAFV600 Mutation-Positive Metastatic Malignancy
Phase 1
Completed
- Conditions
- Malignant Melanoma, Neoplasms
- Interventions
- Registration Number
- NCT01849666
- Lead Sponsor
- Hoffmann-La Roche
- Brief 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 2
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A: phenprocoumon single dose phenprocoumon - B: vemurafenib + phenprocoumon single dose vemurafenib -
- Primary Outcome Measures
Name Time Method Pharmacokinetics of single-dose phenprocoumon under conditions of vemurafenib steady-state exposure: Area under the concentration-time curve (AUC) Pre-dose and up to 168 hours post-dose Pharmacokinetics of single-dose phenprocoumon under conditions of vemurafenib steady-state exposure: Maximum plasma concentration (Cmax) Pre-dose and up to 168 hours post-dose Pharmacokinetics of single-dose phenprocoumon under conditions of vemurafenib steady-state exposure: Time to maximum plasma concentration (Tmax) Pre-dose and up to 168 hours post-dose Pharmacokinetics of single-dose phenprocoumon under conditions of vemurafenib steady-state exposure: Terminal half-life (t1/2) Pre-dose and up to 168 hours post-dose Pharmacokinetics of single-dose phenprocoumon under conditions of vemurafenib steady-state exposure: Apparent clearance (CL/F) Pre-dose and up to 168 hours post-dose
- Secondary Outcome Measures
Name Time Method Safety: Incidence, nature and severity of adverse events (AEs) and serious AEs, graded according to NCI CTCAE Version 4.0 approximately 1.5 years