A Pharmacokinetics Study to Investigate the Effect of Vemurafenib on Digoxin in Patients With BRAFV600 Mutation-Positive Metastatic Melanoma

NCT ID: NCT01765569

Last Updated: 2015-09-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2014-06-30

Brief Summary

This open-label, multi-center, three-period, one sequence study will investigate the effect of vemurafenib on the pharmacokinetics of digoxin in patients with unresectable BRAFV600-mutation positive metastatic melanoma or other malignant tumor type that harbors a V600-activating mutation of BRAF without acceptable standard treatment options. Patients will receive multiple doses of vemurafenib in Periods B and C and a single dose of digoxin in Periods A and C. Eligible patients will have the option to continue treatment with vemurafenib as part of an extension study (NCT01739764). The anticipated time on study treatment is approximately 36 days.

Conditions

Malignant Melanoma, Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vemurafenib + Digoxin

Single oral dose of digoxin 0.25 mg tablet on Day 1 in Period A, followed by vemurafenib 960 mg tablet orally BID from Day 8 to Day 28 in Period B, and then single oral dose of digoxin 0.25 mg on Day 29, and vemurafenib 960 mg orally BID from Day 29 to Day 35 in Period C.

Group Type: EXPERIMENTAL

Digoxin

Intervention Type: DRUG

Participants received single oral dose of digoxin 0.25 mg tablet on Day 1 and Day 29.

Vemurafenib

Intervention Type: DRUG

Participants received vemurafenib 960 mg tablet orally BID from Day 8 to Day 35.

Interventions

Digoxin

Participants received single oral dose of digoxin 0.25 mg tablet on Day 1 and Day 29.

Intervention Type: DRUG

Vemurafenib

Participants received vemurafenib 960 mg tablet orally BID from Day 8 to Day 35.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female patients >= 18 years old
• Patients with either unresectable Stage IIIc or Stage IV metastatic melanoma positive for the BRAFV600 mutation or other malignant tumor type that harbors a V600-activating mutation of BRAF, as determined by results of cobas® 4800 BRAF V600 mutation test or a DNA sequencing method, and who have no acceptable standard treatment options
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
• Life expectancy >= 12 weeks
• Full recovery from the effects of any major surgery or significant traumatic injury within 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 partners of childbearing potential must agree to always use two effective methods of contraception
• Negative serum pregnancy test within 7 days prior to commencement of dosing in women of childbearing potential

Exclusion Criteria

• Prior treatment with vemurafenib or other BRAF inhibitor within 42 days of first dose of study drug
• Prior anti-cancer therapy within 28 days before the first dose of study drug
• History of clinically significant cardiac or pulmonary dysfunction
• History of symptomatic congestive heart failure of any New York Heart Association class or serious cardiac arrhythmia requiring treatment
• History of myocardial infarction within 6 months prior to first dose of study drug
• Current dyspnea at rest, owing to complications of advanced malignancy or any requirement for supplemental oxygen to perform activities of daily living
• History of congenital long QT syndrome or QTc > 450 ms
• Current digoxin therapy or anticipated requirement to take digoxin therapy during the study
• Active central nervous system lesions
• Uncontrolled or poorly controlled diabetes
• Current severe, uncontrolled systemic disease

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Minsk, , Belarus

Minsk District, , Belarus

Vitebsk, , Belarus

Haifa, , Israel

Tel Aviv, , Israel

Tel Litwinsky, , Israel

Kazan', , Russia

Moscow, , Russia

Saint Petersburg, , Russia

Johannesburg, , South Africa

Daegu, , South Korea

Seoul, , South Korea

Seoul, , South Korea

Countries

Belarus; Israel; Russia; South Africa; South Korea

Other Identifiers

2012-003459-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GO28394

Identifier Type: -

Identifier Source: org_study_id