A Study in Cancer Patients to Evaluate the Effect of Lapatinib on the QTc Interval



Status:Completed
Conditions:Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:4/21/2016
Start Date:December 2011
End Date:March 2015

Use our guide to learn which trials are right for you!

A Phase IV, Placebo-controlled Single Sequence Crossover Study to Evaluate the Effect of Repeat Oral Doses of Lapatinib on Cardiac Repolarization in Patients With Advanced Cancer

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.


Inclusion Criteria:

- Histologically or cytologically confirmed diagnosis of: Metastatic breast cancer that
over-expresses ErbB2 OR Recurrent, advanced, or metastatic solid tumor malignancy
(including breast cancer that does not over-express ErbB2) that is refractory to
standard therapies, for which there is no approved therapy, or for which lapatinib in
combination with one of the permitted anti-cancer regimens specified in the
continuation study EGF111767 may provide clinical benefit.

- A female subject must be of non-childbearing potential or willing to use acceptable
contraception.

- A male subject with a female partner of childbearing potential must agree to use
acceptable contraception.

- Is able to swallow and retain oral medication and does not have uncontrolled emesis.

- ECOG performance status 0 to 1.

- Adequate bone marrow function: ANC (absolute neutrophil count) >/=1.5 x 10^9/L,
Hemoglobin >/=9 g/dL, Platelets >/=75 x 10^9/L.

- Albumin >/=3 g/dL.

- Serum bilirubin
- AST and ALT
- Serum Creatinine /= 50 mL/min.

- Serum potassium and magnesium levels within normal limits.

- Has a LVEF within the normal institutional range (or >/=50%).

Exclusion Criteria:

- Any of the following ECG findings: QTcF interval >480 msec, PR interval >240 msec or

- Cardiac conduction abnormalities denoted by any of the following: Evidence of
second-degree (type II) or third-degree atrioventricular block, Evidence of
ventricular pre-excitation, Electrocardiographic evidence of complete left bundle
branch block (LBBB), Intraventricular conduction delay with QRS duration >120 msec,
Atrial fibrillation, Presence of cardiac pacemaker.

- History of any one of the following cardiovascular conditions within the past 6
months: Class III or IV congestive heart failure as defined by the New York Heart
Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable
angina, symptomatic peripheral vascular disease or other clinically significant
cardiac disease.

- Personal history of long-QT syndrome.

- Is pregnant or lactating.

- Has malabsorption syndrome, or has undergone a resection or bypass of the distal
stomach and pylorus, or small bowel.

- Has acute or currently active/requiring anti-viral therapy hepatic or biliary disease
(with the exception of subjects with Gilbert's syndrome, asymptomatic gallstones,
liver metastases or stable chronic liver disease per investigator assessment).

- Has evidence of symptomatic or uncontrolled brain metastases or leptomeningeal
disease. Subjects with brain metastases treated by surgery and/or radiotherapy are
eligible if neurologically stable and do not require steroids or anticonvulsants for
at least 28 days prior to the first dose of study drug.

- Has known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to
drugs chemically related to the investigational product.

- Has received anti-cancer therapy (including chemotherapy, radiation therapy,
immunotherapy, biologic therapy, investigational therapy, surgery, or hormonal
therapy) within 14 days prior to the first dose of study medication.

- Is receiving any prohibited medication or consuming any food or beverage within the
timeframe indicated on the prohibited medication list in the protocol.
We found this trial at
4
sites
Salt Lake City, Utah 84132
?
mi
from
Salt Lake City, UT
Click here to add this to my saved trials
Detroit, Michigan 48202
?
mi
from
Detroit, MI
Click here to add this to my saved trials
Durham, North Carolina 27705
?
mi
from
Durham, NC
Click here to add this to my saved trials
Lebanon, New Hampshire 03756
?
mi
from
Lebanon, NH
Click here to add this to my saved trials