A Pharmacokinetics Study to Investigate the Effect of Vemurafenib on Digoxin in Patients With BRAFV600 Mutation-Positive Metastatic Melanoma
Condition: Malignant Melanoma, Neoplasms
MeSH terms: Melanoma
Intervention: Digoxin; Vemurafenib
Intervention description: Participants received single oral dose of digoxin 0.25 mg tablet on Day 1 and Day 29.; Participants received vemurafenib 960 mg tablet orally BID from Day 8 to Day 35.
Intervention MeSH terms: Vemurafenib; Digoxin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

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