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

Information source: Hoffmann-La Roche
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Malignant Melanoma, Neoplasms

Intervention: acenocoumarol (Drug); vemurafenib (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Hoffmann-La Roche

Official(s) and/or principal investigator(s):
Clinical Trials, Study Director, Affiliation: Hoffmann-La Roche

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 patients with BRAFV600 mutation-positive metastatic malignancies. Patients will receive a single dose of acenocoumarol 4 mg orally on Day 1, vemurafenib 960 mg orally twice daily on Days 4-23 and a single dose of acenocoumarol 4 mg on Day 23. After completion of pharmacokinetic assessments on Day 26, eligible patients will have the option to continue treatment with vemurafenib as part of an extension study.

Clinical Details

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 design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Primary outcome:

Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Area under the concentration-time curve (AUC)

Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Maximum plasma concentration (Cmax)

Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Time to maximum plasma concentration (Tmax)

Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Terminal half-life (t1/2)

Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Apparent clearance (CL/F)

Secondary outcome: Safety: Incidence, nature and severity of adverse events (AEs) and serious AEs, graded according to NCI CTCAE Version 4.0

Eligibility

Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.

Criteria:

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 acenocoumarol 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

Locations and Contacts

Buxtehude 21614, Germany

Essen 45122, Germany

Mannheim 68167, Germany

Crete 71110, Greece

Thessaloniki 56429, Greece

Budapest 1122, Hungary

Amsterdam 1066 CX, Netherlands

Maastricht 6229HX, Netherlands

Utrecht 3584 CX, Netherlands

Auckland 1142, New Zealand

Christchurch 8011, New Zealand

Lisboa 1099-023, Portugal

Porto 4200-072, Portugal

Belgrade 11000, Serbia

Barcelona 08036, Spain

Madrid 28031, Spain

Madrid 28040, Spain

Madrid 28050, Spain

L'Hospitalet de Llobregat, Barcelona 08908, Spain

Wodonga, New South Wales 3690, Australia

Additional Information

Starting date: August 2013
Last updated: August 17, 2015

Page last updated: August 20, 2015

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