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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

Phase 4
18 Years
Open (Enrolling)

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Trial Information

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

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

- 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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Outcome Measure:

• The primary enpoint will be the change in baseline adjusted QTcF interval at each time point for lapatinib (average of at least 3 Holter ECG replicates per time point) as compared with time-matched placebo

Outcome Time Frame:

From Study Day 1 until Study Day 5

Safety Issue:


Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

November 2011

Completion Date:

July 2014

Related Keywords:

  • Cancer
  • cancer
  • cardiac repolarization
  • Holter monitor
  • pharmacokinetics
  • GW572016
  • lapatinib
  • QTc interval
  • safety
  • ECG



GSK Investigational Site Raleigh, North Carolina  27609
GSK Investigational Site Hooksett, New Hampshire  03106
GSK Investigational Site Salt Lake City, Utah  84107