A study in cancer patients to evaluate the effect of lapatinib on the QTc interval
Trial overview
Treatment Difference in duration of cardiac ventricular depolarization and repolarization interval (QT) in Fridericia-corrected QT interval (QTcF) values between placebo and lapatinib 2000mg
Timeframe: Baseline (BL) (Day1) and pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24-hours (hr) post-dose on Day 2 for placebo (PBO). Baseline (Day 3) and pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24-hours post-dose on Day 4 for lapatinib (LAP).
Change from Baseline in the Holter ECG parameters of QT interval, corrected QT interval (QTc), Bazett corrected QTc interval (QTcB), individual-corrected QT interval (QTcI), RR interval, PR interval, and QRS duration at indicated time points
Timeframe: Baseline (Day1) and pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24-hours post-dose on Day 2 for placebo. Baseline (Day 3) and pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24-hours post-dose on Day 4 for lapatinib.
Number of participants with 12-lead Holter ECG findings at the indicated time points
Timeframe: Baseline (Day1) and pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24-hours post-dose on Day 2 for placebo. Baseline (Day 3) and pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24-hours post-dose on Day 4 for lapatinib.
Number of participants with the worst-case post-Baseline 12-lead Holter ECG findings with significant ST, T wave, and U wave abnormalities
Timeframe: Baseline (Day1) and pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24-hours post-dose on Day 2 for placebo. Baseline (Day 3) and pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24-hours post-dose on Day 4 for lapatinib.
Number of participants with any adverse event (AE) or serious adverse event (SAE)
Timeframe: From the start of study treatment until follow-up (within approximately 28 days following the last dose of study medication [up to end of Study Week 4])
Mean albumin, and hemoglobin at the indicated time points
Timeframe: Baseline; Day 5 and end of study visit on Day 8-11
Mean alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) at the indicated time points
Timeframe: Baseline; Day 5 and end of study visit on Day 8-11
Mean direct bilirubin, total bilirubin, and creatinine at the indicated time points
Timeframe: Baseline; Day 5 and end of study visit on Day 8-11
Mean calcium, chloride, carbon dioxide (CO2), potassium, sodium, magnesium and urea at the indicated time points
Timeframe: Baseline; Day 5 and end of study visit on Day 8-11
Mean total neutrophils (ANC [absolute neutrophil count]), platelets and leukocyte count at the indicated time points
Timeframe: Baseline; Day 5 and end of study visit on Day 8-11
Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the indicated time points
Timeframe: Baseline; on Day 2 (at pre-dose, 4, 8, 12 and 24 hours post-dose), and on Day 4 (at pre-dose, 4, 8, 12 and 24 hours post-dose)
Change from Baseline in heart rate at the indicated time points
Timeframe: Baseline; on Day 2 (at pre-dose, 4, 8, 12 and 24 hours post dose), and on Day 4 (at pre-dose, 4, 8, 12 and 24 hours post dose
Number of participants with 12-lead ECG findings at indicated time points
Timeframe: BL;Day 1 (at pre-dose);Day 2 (at pre-dose, 4, 8, 12 and 24 hr post dose);Day 4 (at pre-dose, 4, 8, 12 and 24 hr post dose);End of Study visit (Day 8-11); and Follow-up (within approx 28 days following last dose of study trt [up to end of Study Week 4])
Mean area under the plasma drug concentration-time curve (AUC) from time zero (pre-dose) to the last time of quantifiable concentration (AUC[0-t]) and from time zero (pre-dose) to 24 hours post dose (AUC[0-24]) for lapatinib
Timeframe: Day 1 pre-dose; on Day 2 (at pre-dose, then 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-last-dose), and on Day 4 (at pre-dose, then 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-last-dose)
Mean maximum plasma concentration (Cmax) and observed plasma concentration at 24 hours post-dose (C24) of lapatinib
Timeframe: Day1 pre-dose; on Day 2 (at pre-dose, then 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose), and on Day 4 (at pre-dose, then 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose)
Median time to Cmax (tmax) and the time prior to the first quantifiable (non-zero) lapatinib plasma concentration (tlag) following the last (3rd) lapatinib dose
Timeframe: Day 1 pre-dose; on Day 2 (at pre-dose, then 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose), and on Day 4 (at pre-dose, then 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose)
Participation 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.
- 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.
- 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%).
- 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.
Trial location(s)
Study documents
No study documents available.
Results overview
Results posted on ClinicalTrials.gov
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.