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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 2
- Primary Endpoint
- Pharmacokinetics of single-dose phenprocoumon under conditions of vemurafenib steady-state exposure: Area under the concentration-time curve (AUC)
Study Overview
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).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
A: phenprocoumon single dose
Intervention: phenprocoumon (Drug)
B: vemurafenib + phenprocoumon single dose
Intervention: vemurafenib (Drug)
Outcomes
Primary Outcomes
Pharmacokinetics of single-dose phenprocoumon under conditions of vemurafenib steady-state exposure: Area under the concentration-time curve (AUC)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: Pre-dose and up to 168 hours post-dose
Secondary Outcomes
- Safety: Incidence, nature and severity of adverse events (AEs) and serious AEs, graded according to NCI CTCAE Version 4.0(approximately 1.5 years)