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: Drug: phenprocoumon; Drug: vemurafenib

• 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

Study Timeline

• Study First Submitted: 2013-05-03
• Study First Submitted QC: 2013-05-03
• Study First Posted: 2013-05-08
• Study Start: 2013-09
• Primary Completion: 2014-04
• Study Completion: 2014-04
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-01
• Last Update Posted: 2016-11-02

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