Conditions: Cancer
Keywords: cancer cardiac repolarization Holter monitor pharmacokinetics GW572016 lapatinib QTc interval safety ECG
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 58
Healthy volunteers: no

Brief summary:
This study will estimate the effect of lapatinib on cardiac repolarization (QTc interval duration) in subjects with advanced solid tumors. The study treatment period will occur over five days and an End of Study visit will be conducted on Day 8 (or no later than 3 days beyond Day 8). Subjects will receive placebo that mimics lapatinib for 2 days as three separate doses given 12 hours apart (8 tablets/dose) and lapatinib (2000mg) for 2 days as three separate doses given 12 hours apart (8 tablets/dose). Subjects will not know when they are receiving placebo vs. lapatinib. Digital 12-lead ECG recordings will be extracted from continuous ECG recordings obtained via a Holter monitor to measure QTc interval duration. Triplicate ECG measurements of QTc interval will be taken at pre-specified times at Day 1 (Baseline) and pre-dose and up to 24 hours after the third dose of placebo or lapatinib on Study Days 2 and 4. Pharmacokinetic sampling will occur immediately following each pre-specified QTc measurement in subjects dosed with placebo or lapatinib. Subjects who complete participation in this study, if they are eligible, will be offered the option to continue treatment with lapatinib, either alone or in combination with other oncology drugs in pre-selected anticancer regimens, in a continuation protocol, EGF111767.

Detailed description:

Arms:
arm 1: This is a crossover study where subjects will receive placebo that mimics lapatinib for 2 days and lapatinib for 2 days. Subjects will not know when they are receiving placebo vs. lapatinib.

Interventions: intervention 1: lapatinib intervention 2: placebo matching lapatinib
Intervention descriptions: intervention 1: lapatinib commercial tablet, 2000mg, will be given as three separate doses (8 tablets/dose) given 12 hours apart over a 2 day period intervention 2: placebo matching lapatinib will be given as three separate doses (8 tablets/dose) given 12 hours apart over a 2 day period

Protocol document: