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An Open-label, Randomized, Adaptive Design, Two-period Crossover Study in Cancer Patients to Evaluate the Bioequivalence of Alternative Formulations of Lapatinib Compared to the Commercial Tablet

Phase 1
18 Years
Open (Enrolling)
ErbB2 Overexpressing, Solid Tumors, Metastatic Breast Cancer, Neoplasms, Breast

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Trial Information

An Open-label, Randomized, Adaptive Design, Two-period Crossover Study in Cancer Patients to Evaluate the Bioequivalence of Alternative Formulations of Lapatinib Compared to the Commercial Tablet

Inclusion Criteria:

- Histologically or cytologically confirmed diagnosis of: Metastatic breast cancer
that over-expresses ErbB2 (3+ by IHC; FISH or CISH positive)and the subject has
received prior therapy including an anthracycline, a taxane, and trastuzumab 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.

- Is at least 18 years of age.

- 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 is: Pre-menopausal with a documented bilateral oophorectomy
(ovariectomy), bilateral tubal ligation, or hysterectomy. Post-menopausal defined as
total cessation of menses for >/=12 months (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 contraception methods listed in
the protocol for the time period from 14 days prior to the first dose of study drug
until 30 days post the last dose of study drug to sufficiently minimize the risk of
pregnancy at that point.

- Subject is a man with a female partner of childbearing potential who agrees to use

- Is able to swallow and retain oral medication and does not have uncontrolled emesis
regardless of etiology.

NOTE: If subject has a current or recent (within 14 days) history of nausea or emesis, the
subject must be reviewed by the Investigator and the GSK medical monitor. Prophylactic
antiemetic therapy may be appropriate.

- ECOG performance status 0 to 1.

- 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). NOTE: Transfusions
of blood and blood products as well as growth factor support are prohibited within 14
days prior to the first dose of study drug.

- Calculated creatinine clearance (CrCl) >/= 50 ml/min based on Cockcroft and Gault.

- Total bilirubin
- Alanine transaminase (ALT) without liver metastases.

- Has a LVEF within the normal institutional range (or >/= 50%) based on ECHO or MUGA.

- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.

Exclusion Criteria:

- Is pregnant or lactating.

- Has malabsorption syndrome, a disease affecting gastrointestinal function, a GI tract
bypass in place, or has undergone a resection of the distal stomach and pylorus,
small bowel, or ascending or transverse colon that could impact lapatinib absorption.

NOTE: Resection of the gastric antrum, the appendix, descending colon, sigmoid colon and
rectum are permitted if there is no overt evidence of malabsorption.

- Has acute or currently active (e.g.,requiring anti-viral therapy) 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 for
at least 28 days prior to the first dose of study drug.

- 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 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 lapatinib.

NOTE: Any ongoing potentially reversible toxicity from prior anti-cancer therapy that is
> Grade 1 (except alopecia or Grade 2 neuropathy that has been stable for at least 4
weeks) or any toxicity from prior anti-cancer therapy that is progressing in severity will
render the subject ineligible unless agreed to by the GSK Medical Monitor and the

- Is receiving any prohibited medication or consuming any food or beverage within the
timeframe indicated on the prohibited medication list.

- Has physiological, familial, sociological, or geographical conditions that do not
permit compliance with the protocol.

- Clinically significant ECG abnormality including baseline QTc prolongation >480msec.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The primary PK endpoints will be AUC(0-24) and Cmax of lapatinib

Outcome Time Frame:

Period 1 Day 7 and Period 2 Day 7

Safety Issue:


Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:



Korea: Korea Food & Drug Administration

Study ID:




Start Date:

November 2009

Completion Date:

November 2012

Related Keywords:

  • ErbB2 Overexpressing
  • Solid Tumors
  • Metastatic Breast Cancer
  • Neoplasms, Breast
  • bioequivalence, lapatinib, GW572016
  • Breast Neoplasms
  • Neoplasms



GSK Investigational SitePhoenix, Arizona  85013 - 4496
GSK Investigational SiteGainesville, Florida  32610
GSK Investigational SiteSavannah, Georgia  31405
GSK Investigational SiteRoyal Oak, Michigan  48073
GSK Investigational SiteGermantown, Tennessee  38138
GSK Investigational SiteWashington, District of Columbia  20307-5001