A Study to Examine the Effects of Low and High-fat Meals on Orally Administered Lapatinib in Metastatic ErbB2 Positive Breast Cancer Patients

NCT00821054 | Completed Phase 1

• 1 other identifier: 111582
• Study Type: interventional
• Target: 24
• Locations: 3 countries
• Sites: 5

Brief Summary

This study will be a randomized 3-treatment, cross-over study to evaluate the bioavailability of lapatinib administered after a high or low-fat meal.

Conditions

Neoplasms, Breast

Keywords

Phase I Food Effect

Outcome Measures

Primary Outcomes (1)

• Protocol specified pharmacokinetic parameters

  3 weeks

Secondary Outcomes (1)

• Safety and tolerability as assessed by evaluation of adverse events (AEs), changes in laboratory values, and vital signs

  3 weeks

Study Arms (3)

Period 1

EXPERIMENTAL

Treatment A, B or C

Drug: Lapatinib

Period 2

EXPERIMENTAL

Treatment A, B or C

Drug: Lapatinib

Period 3

EXPERIMENTAL

Treatment A, B or C

Drug: Lapatinib

Interventions

Lapatinib DRUG

Treatment A: one dose of 1250mg lapatinib 1 hour before starting a low-fat breakfast; Treatment B: one dose of 1250mg lapatinib 1 hour after finishing a low fat breakfast; or Treatment C: one dose of 1250mg lapatinib 1 hour after finishing a high-fat breakfast.

Also known as: TYKERB - US; TYVERB - UK

Period 1; Period 2; Period 3

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Metastatic, histologically confirmed breast cancer that over-expresses ErbB2 (3+ by IHC; FISH or CISH positive).
• Is at least 18 years of age and not greater than 65 years of age.
• Is male or female. A female is eligible to enter and participate in the study if she is of:
• Non-childbearing potential (i.e. physiologically incapable of becoming pregnant), including any female who: has had a hysterectomy; has had a bilateral oophorectomy (ovariectomy); has had a bilateral tubal ligation, or is post-menopausal (a demonstration of total cessation of menses for ≥ 1 year) or in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/ml and estradiol \< 40 pg/ml (\<140 pmol/L) is confirmatory.
• Childbearing potential, has a negative serum pregnancy test at Screening and agrees to one of the following: double-barrier contraception (condom with spermicidal jelly, foam, suppository, or film; diaphragm with spermicide; or male condom and diaphragm); complete abstinence from sexual intercourse from two weeks prior to administration of the study drug, throughout the active study treatment period; vasectomized partner who is sterile prior to the female subject's entry and is the sole sexual partner for that female.
• Is able to swallow and retain oral medication.
• ECOG performance status 0 to 2.
• Adequate bone marrow function.
• Hemoglobin ≥ 9 gm/dL.
• Absolute granulocyte count ≥1,500/mm3 (1.5 x 109/L).
• Platelets ≥ 75,000/mm3 (75 x 109/L).
• Calculated creatinine clearance (CrCl) ≥ 50 ml/min based on Cockcroft and Gault
• Total bilirubin ≤ 1.5 X upper limit of normal of institutional values and INR ≤ 1.5.
• Alanine transaminase (ALT) ≤ three times the upper limit of the institutional values or ≤ five times ULN with documented liver metastases.
• Has a left ventricular ejection fraction (LVEF) within the normal institutional range based on ECHO or MUGA.

You may not qualify if:

• Is pregnant or lactating.
• 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 as a result of the medical interview, physical exam, or screening investigations.
• Has a known immediate or delayed 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.
• 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.
• Is receiving any prohibited medication within the timeframe indicated on the prohibited medication list for this study.
• 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 (ECG) abnormality.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• Has consumed 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 7 days prior to the first dose of study medication.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (5)

GSK Investigational Site

Buffalo, New York, 14263, United States

Location

GSK Investigational Site

Greenville, South Carolina, 29605, United States

Location

GSK Investigational Site

Edmonton, Alberta, T6G 1Z2, Canada

Location

GSK Investigational Site

Montreal, Quebec, H2W 1T8, Canada

Location

GSK Investigational Site

Amsterdam, 1066 CX, Netherlands

Location

Related Publications (1)

• Devriese LA, Koch KM, Mergui-Roelvink M, Matthys GM, Ma WW, Robidoux A, Stephenson JJ, Chu QS, Orford KW, Cartee L, Botbyl J, Arya N, Schellens JH. Effects of low-fat and high-fat meals on steady-state pharmacokinetics of lapatinib in patients with advanced solid tumours. Invest New Drugs. 2014 Jun;32(3):481-8. doi: 10.1007/s10637-013-0055-4. Epub 2013 Dec 19.

  PMID: 24346280 DERIVED

Related Links

• Results for study 111582 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Lapatinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2008
• First Posted: January 12, 2009
• Study Start: March 6, 2009
• Primary Completion: March 22, 2011
• Study Completion: March 22, 2011
• Last Updated: November 13, 2017

Record last verified: 2017-11

Locations

CA (2); US (2); NL (1)