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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by GlaxoSmithKline
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01328054
First received: March 10, 2011
Last updated: July 24, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Cancer
Drug: lapatinib
Drug: placebo matching lapatinib
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • • 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 [ Time Frame: From Study Day 1 until Study Day 5 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • • ECG parameters: RR interval, QT, QTcB, QTci, heart rate, PR, QRS intervals and morphology [ Time Frame: From Study Day 1 until Study Day 5 ] [ Designated as safety issue: Yes ]
  • • Plasma lapatinib concentrations and pharmacokinetic parameters AUC(0-t), AUC(0-24), C24, Cmax, tlag, and tmax [ Time Frame: From Study Day 1 until Study Day 5 ] [ Designated as safety issue: No ]
  • • Safety parameters: AEs, vital signs, ECGs and clinical laboratory assessments [ Time Frame: From Study Day 1 until completion of the study ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 48
Study Start Date: November 2011
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: lapatinib/placebo
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.
Drug: lapatinib
lapatinib commercial tablet, 2000mg, will be given as three separate doses (8 tablets/dose) given 12 hours apart over a 2 day period
Drug: placebo matching lapatinib
placebo matching lapatinib will be given as three separate doses (8 tablets/dose) given 12 hours apart over a 2 day period

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 </=1.5 x ULN.
  • AST and ALT </=3 x ULN .
  • Serum Creatinine </=1.5 mg/dL or Calculated Creatinine Clearance >/= 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 </=110 msec, Bradycardia defined as sinus rate <50 beats per minute.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01328054

Contacts
Contact: US GSK Clinical Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

Locations
United States, Michigan
GSK Investigational Site Recruiting
Detroit, Michigan, United States, 48202
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
United States, New Hampshire
GSK Investigational Site Recruiting
Lebanon, New Hampshire, United States, 03756
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
United States, North Carolina
GSK Investigational Site Recruiting
Durham, North Carolina, United States, 27710
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
United States, Utah
GSK Investigational Site Recruiting
Salt Lake City, Utah, United States, 84112
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01328054     History of Changes
Other Study ID Numbers: 114271
Study First Received: March 10, 2011
Last Updated: July 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
cancer
cardiac repolarization
Holter monitor
pharmacokinetics
GW572016
lapatinib
QTc interval
safety
ECG

Additional relevant MeSH terms:
Lapatinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014