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

• Pharmacokinetics: Area under the concentration time curve [ Time Frame: Approximately 36 days ] [ Designated as safety issue: No ]
• Pharmacokinetics: Maximum plasma concentration [ Time Frame: Approximately 36 days ] [ Designated as safety issue: No ]
• Pharmacokinetics: Time to maximum plasma concentration [ Time Frame: Approximately 36 days ] [ Designated as safety issue: No ]
• Pharmacokinetics: Terminal half-life [ Time Frame: Approximately 36 days ] [ Designated as safety issue: No ]
• Pharmacokinetics: Apparent clearance [ Time Frame: Approximately 36 days ] [ Designated as safety issue: No ]

This open-label, multi-center, three-period, one sequence study will investigate the effect of vemurafenib on the pharmacokinetics digoxin of 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. The anticipated time on study treatment is approximately 36 days.

• Drug: vemurafenib
  Multiple doses of vemurafenib in Periods B and C
• Drug: digoxin
  Single dose of digoxin in Periods A and C

• Experimental: Vemurafenib treatment
  Intervention: Drug: vemurafenib
• Experimental: Digoxin treatment
  Intervention: Drug: digoxin

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