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

Phase 1

Withdrawn

• Conditions: Malignant Melanoma, Neoplasms
• Interventions: Drug: ketoconazole; Drug: vemurafenib

• Registration Number: NCT01765556
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

This open-label, multi-center, three-period, one sequence study will investigate the effect of ketoconazole on the pharmacokinetics of vemurafenib 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 a single dose of vemurafenib in Periods A and C and multiple doses of ketoconazole in Periods B 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 19 days.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-01-09
• Study First Submitted QC: 2013-01-09
• Study First Posted: 2013-01-10
• Study Start: 2013-10
• Primary Completion: 2013-10
• Study Completion: 2013-10
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-01
• Last Update Posted: 2016-11-02

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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
• Requirement for immediate or urgent treatment with daily vemurafenib and for whom the intermittent schedule of vemurafenib employed during the 19-day period for this trial is not clinically acceptable
• Allergy or hypersensitivity to components of the vemurafenib formulation
• Experimental therapy within 4 weeks prior to first dose of study drug
• Major surgical procedure or significant traumatic injury within 14 days prior to first dose of study drug or anticipation of the need for major surgery during study treatment
• 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
• Active central nervous system lesions
• Uncontrolled or poorly controlled diabetes
• Current severe, uncontrolled systemic disease

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ketoconazole treatment	ketoconazole	-
Vemurafenib treatment	vemurafenib	-

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics: Maximum plasma concentration	Approximately 19 days
Pharmacokinetics: Apparent clearance	Approximately 19 days
Pharmacokinetics: Terminal half-life	Approximately 19 days
Pharmacokinetics: Time to maximum plasma concentration	Approximately 19 days
Pharmacokinetics: Area under the concentration time curve	Approximately 19 days

Secondary Outcome Measures

Name	Time	Method
Safety: Incidence of adverse events	Approximately 19 days