A Study to Examine the Effects of Esomeprazole on the Pharmacokinetics of Orally Administered Lapatinib in Subjects With Metastatic ErbB2 Positive Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00849329
First received: February 12, 2009
Last updated: May 17, 2012
Last verified: March 2011
  Purpose

This study will characterize the effect of elevated gastric pH mediated by the proton-pump inhibitor, esomeprazole, on the relative bioavailability of lapatinib in subjects with metastatic ErbB2 positive breast cancer.


Condition Intervention Phase
Neoplasms, Breast
Advanced or Metastatic ErbB2-overexpressing Breast Cancer
Drug: lapatinib
Drug: lapatinib plus esomeprazole
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Single Sequence Study to Examine the Effects of Esomeprazole on the Pharmacokinetics of Orally Administered Lapatinib in Subjects With Metastatic ErbB2 Positive Breast Cancer

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • The area under the concentration versus time curve, minimum observed concentration, maximum observed concentration, time at which it occurs, and lag time in the appearance of measurable plasma concentrations of lapatinb [ Time Frame: Continue until disease progression or withdrawal consent ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and tolerability assessments including evaluation of adverse events and changes in laboratory values, and vital signs. [ Time Frame: Continue until disease progression or withdrawal consent ] [ Designated as safety issue: Yes ]

Enrollment: 16
Study Start Date: March 2009
Study Completion Date: February 2010
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Period 1
1250mg lapatinib once daily in the morning
Drug: lapatinib
1250mg lapatinib
Experimental: Period 2
1250mg lapatinib once daily in the morning in combination with esomeprazole 40mg once daily at bedtime.
Drug: lapatinib plus esomeprazole
1250mg lapatinib plus esomeprazole 40mg

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Metastatic, histologically confirmed breast cancer that overexpresses ErbB2 (3+ by IHC, FISH, or CISH positive).
  • 18 years to 65 years of age.
  • Is male or female (of non childbearing potential or willing to use contraception as specified in the protocol).
  • Is able to swallow and retain oral medication.
  • ECOG performance status 0 to 2.
  • Provided written informed consent.
  • Adequate bone marrow function (as specified in the protocol).
  • Calculated creatinine clearance (CrCl) greater than or equal to 50 ml/min based on Cockcroft and Gault.
  • Total bilirubin less than or equal to 1.5 X upper limit of normal of institutional values.
  • Alanine transaminase (ALT) less than or equal to 3 times the upper limit of the institutional values or less than or equal to 5 times ULN with documented liver metastases
  • Has a left ventricular ejection fraction (LVEF) within the normal institutional range based on ECHO or MUGA.
  • Life expectancy of greater than or equal to 12 weeks
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria:

  • Pregnant or lactating woman.
  • Has malabsorption syndrome, a disease affecting gastrointestinal function, or resection of the stomach or small bowel.
  • Has current active hepatic or biliary disease (with exception of patients 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.
  • Is considered medically unfit for the study by the investigator.
  • Has a known immediate or delayed benzimidazole hypersensitivity reaction or idiosyncrasy to drugs chemically related to the investigational product such as gefitinib [Iressa] and erlotinib [Tarceva].
  • Has received treatment with any investigational drug in the previous four weeks. (with the exception of lapatinib).
  • Has received chemotherapy, immunotherapy, biologic therapy or hormonal therapy for the treatment of cancer within the past 14 days, with the exception of mitomycin C which is restricted for the past six weeks, and lapatinib. Subjects receiving lapatinib prior to study entry are eligible to participate in the study.
  • Is receiving any prohibited medication within the timeframe indicated on the prohibited medication list in the protocol.
  • Has physiological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
  • Has inadequate venous access for protocol-related blood draws.
  • Clinically significant electrocardiogram abnormality.
  • History of sensitivity to heparin or heparin-induced thrombocytopenia.
  • Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or kumquats, pummelos, exotic citrus fruit (i.e. star fruit, bitter melon), grapefruit hybrids or fruit juices from seven days prior to the first dose of study medication.
  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: NCT00849329

Locations
United States, South Carolina
GSK Investigational Site
Greenville, South Carolina, United States, 29605
Korea, Republic of
GSK Investigational Site
Seoul, Korea, Republic of, 135-710
GSK Investigational Site
songpa-gu, Seoul, Korea, Republic of, 138-736
Spain
GSK Investigational Site
Hospitalet de Llobregat (Barcelona), Spain, 08907
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00849329     History of Changes
Other Study ID Numbers: 109275
Study First Received: February 12, 2009
Last Updated: May 17, 2012
Health Authority: Spain: Agencia Española del Medicamento y Productos Sanitarios
Canada: Biologics and Genetics Therapeutic Directorate (B>D)
United States: Institutional Review Board
South Korea: Food and Drug Administration
United States: Food and Drug Administration
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by GlaxoSmithKline:
lapatinib (GW572016), subject, pharmacokinetic, esomeprazole, proton-pump inhibitor, drug interaction, Phase 1

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Esomeprazole
Lapatinib
Anti-Ulcer Agents
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on August 20, 2014