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

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT01851824
Collaborator
(none)
9
Enrollment
20
Locations
1
Arm
10
Duration (Months)
0.5
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This open-label, multicenter, 3-period, fixed-sequence study will evaluate the effect of multiple doses of vemurafenib on the pharmacokinetics of a single dose of acenocoumarol in participants with BRAFV600 mutation-positive metastatic malignancies. Participants will receive a single dose of acenocoumarol 4 mg orally on Day 1 and Day 23, vemurafenib 960 mg orally twice daily on Days 4-26. After completion of pharmacokinetic assessments on Day 26, eligible participants will have the option to continue treatment with vemurafenib as part of an extension study (GO28399 [NCT01739764]).

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
9 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Official Title:
A PHASE I, OPEN-LABEL, MULTICENTER, 3-PERIOD, FIXED-SEQUENCE STUDY TO INVESTIGATE THE EFFECT OF VEMURAFENIB ON THE PHARMACOKINETICS OF A SINGLE ORAL DOSE OF ACENOCOUMAROL IN PATIENTS WITH BRAFV600 MUTATION-POSITIVE METASTATIC MALIGNANCY
Study Start Date :
Aug 1, 2013
Actual Primary Completion Date :
Jun 1, 2014
Actual Study Completion Date :
Jun 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: Acenocoumarol + Vemurafenib

Drug: acenocoumarol
4 mg single oral doses on Days 1 and 23

Drug: vemurafenib
960 mg orally bid, 20 days (Days 4-23)
Other Names:
  • Zelboraf

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Area under the concentration-time curve (AUC) [Pre-dose and up to 72 hours post-dose]

    2. Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Maximum plasma concentration (Cmax) [Pre-dose and up to 72 hours post-dose]

    3. Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Time to maximum plasma concentration (Tmax) [Pre-dose and up to 72 hours post-dose]

    4. Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Terminal half-life (t1/2) [Pre-dose and up to 72 hours post-dose]

    5. Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Apparent clearance (CL/F) [Pre-dose and up to 72 hours post-dose]

    Secondary Outcome Measures

    1. Safety: Incidence of Adverse Events and Serious Adverse Events [approximately 1.5 years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    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. participants with radiographically unstable, symptomatic lesions)

    • History of bleeding or coagulation disorders

    • Allergy or hypersensitivity to vemurafenib or acenocoumarol formulations

    • History of malabsorption or other condition that would interfere with the enteral absorption of study treatment

    • Participants with VKORC1 mutations (1639G→A, 1173C→T) in either one allele (heterozygous)or two alleles (homozygous)

    • Participants with CYP2C9*3 mutations in either one allele (heterozygous) or two alleles (homozygous)

    • 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Wodonga New South Wales Australia 3690
    2 Buxtehude Germany 21614
    3 Essen Germany 45122
    4 Mannheim Germany 68167
    5 Crete Greece 71110
    6 Thessaloniki Greece 56429
    7 Budapest Hungary 1122
    8 Amsterdam Netherlands 1066 CX
    9 Maastricht Netherlands 6229HX
    10 Utrecht Netherlands 3584 CX
    11 Auckland New Zealand 1142
    12 Christchurch New Zealand 8011
    13 Lisboa Portugal 1099-023
    14 Porto Portugal 4200-072
    15 Belgrade Serbia 11000
    16 Barcelona Spain 08036
    17 Barcelona Spain 08908
    18 Madrid Spain 28031
    19 Madrid Spain 28040
    20 Madrid Spain 28050

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT01851824
    Other Study ID Numbers:
    • GO28397
    • 2012-003706-27
    First Posted:
    May 13, 2013
    Last Update Posted:
    Nov 2, 2016
    Last Verified:
    Nov 1, 2016
    Additional relevant MeSH terms:
    Melanoma
    Vemurafenib
    Acenocoumarol

    Study Results

    No Results Posted as of Nov 2, 2016