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

• Status: Withdrawn
• Trial end date: 2013-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hoffmann-La Roche
• Treatments: Ketoconazole; Vemurafenib

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

• 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