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

Malignant Melanoma, Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01851824
• Other study ID #: GO28397
• Secondary ID: 2012-003706-27
• Status: Completed
• Phase: Phase 1
• First received: May 3, 2013
• Last updated: November 1, 2016
• Start date: August 2013
• Est. completion date: June 2014

Study information

• Verified date: November 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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]).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Malignant Melanoma, Neoplasms
• Melanoma

Intervention

Drug:
• acenocoumarol
4 mg single oral doses on Days 1 and 23
• vemurafenib
960 mg orally bid, 20 days (Days 4-23)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Australia,  Germany,  Greece,  Hungary,  Netherlands,  New Zealand,  Portugal,  Serbia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	Safety: Incidence of Adverse Events and Serious Adverse Events		approximately 1.5 years	No