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

Roche

Status and phase

Withdrawn

Phase 1

Conditions

Malignant Melanoma, Neoplasms

Treatments

Drug: ketoconazole

Drug: vemurafenib

Study type

Interventional

Funder types

Industry

Identifiers

NCT01765556

GO28054

2012-003143-29 (EudraCT Number)

Details and patient eligibility

About

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.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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