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

NCT01851824 | Completed Phase 1

• 2 other identifiers: GO283972012-003706-27
• Study Type: interventional
• Target: 9
• Locations: 9 countries
• Sites: 20

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 \[NCT01739764\]).

Conditions

Malignant Melanoma, Neoplasms

Outcome Measures

Primary Outcomes (5)

• 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

• 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

• 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

• 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

• 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 Outcomes (1)

• Safety: Incidence of Adverse Events and Serious Adverse Events

  approximately 1.5 years

Study Arms (1)

Acenocoumarol + Vemurafenib

EXPERIMENTAL

Drug: acenocoumarol; Drug: vemurafenib

Interventions

acenocoumarol DRUG

4 mg single oral doses on Days 1 and 23

Acenocoumarol + Vemurafenib

vemurafenib DRUG

960 mg orally bid, 20 days (Days 4-23)

Also known as: Zelboraf

Acenocoumarol + Vemurafenib

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (20)

Unknown Facility

Wodonga, New South Wales, 3690, Australia

Location

Unknown Facility

Buxtehude, 21614, Germany

Location

Unknown Facility

Essen, 45122, Germany

Location

Unknown Facility

Mannheim, 68167, Germany

Location

Unknown Facility

Crete, 71110, Greece

Location

Unknown Facility

Thessaloniki, 56429, Greece

Location

Unknown Facility

Budapest, 1122, Hungary

Location

Unknown Facility

Amsterdam, 1066 CX, Netherlands

Location

Unknown Facility

Maastricht, 6229HX, Netherlands

Location

Unknown Facility

Utrecht, 3584 CX, Netherlands

Location

Unknown Facility

Auckland, 1142, New Zealand

Location

Unknown Facility

Christchurch, 8011, New Zealand

Location

Unknown Facility

Lisbon, 1099-023, Portugal

Location

Unknown Facility

Porto, 4200-072, Portugal

Location

Unknown Facility

Belgrade, 11000, Serbia

Location

Unknown Facility

Barcelona, Barcelona, 08036, Spain

Location

Unknown Facility

Barcelona, Barcelona, 08908, Spain

Location

Unknown Facility

Madrid, Madrid, 28031, Spain

Location

Unknown Facility

Madrid, Madrid, 28040, Spain

Location

Unknown Facility

Madrid, Madrid, 28050, Spain

Location

MeSH Terms

Conditions

Melanoma; Neoplasms

Interventions

Acenocoumarol; Vemurafenib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2013
• First Posted: May 13, 2013
• Study Start: August 1, 2013
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: November 2, 2016

Record last verified: 2016-11

Locations

SE (1); DE (3); ES (5); NL (3); AU (1); PT (2); GR (2); NZ (2); HU (1)