Phase 1 Completed N=29 Treatment

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

Malignant Melanoma, Neoplasms

Source: ClinicalTrials.gov NCT01765569 ↗

Enrolled (actual)

Serious AEs

3.5%

Results posted

Aug 2015

Primary outcomePrimary: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of Digoxin — 14.9; 27.7 hour*ng/mL

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.

Outcome Measures

Outcome	Result	p-value
PRIMARY Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of Digoxin	14.9; 27.7	—
PRIMARY Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Digoxin	18.5; 35.4	—
PRIMARY Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC24) of Digoxin	7.73; 10.6	—
PRIMARY Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC168) of Digoxin	18.2; 29.7	—
PRIMARY Maximum Plasma Concentration (Cmax) of Digoxin	1.36; 1.99	—
PRIMARY Time to Maximum Plasma Concentration (Tmax) of Digoxin	1; 1	—
PRIMARY Terminal Half-Life (t1/2) of Digoxin	35; 56.4	—
PRIMARY Apparent Clearance (CL/F) of Digoxin	14.5; 7.15	—

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01765569). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.