A Double Blind Short-Term Presurgical Study Assessing the Molecular Antiproliferative Predictors of Lapatinib's Effects in Breast Cancer

Institute of Cancer Research, United Kingdom1 site in 1 country121 target enrollmentJune 2007

ConditionsBreast Cancer

InterventionsLapatinib Lapatinib-Placebo

DrugsLapatinib Lapatinib-Placebo

Overview

Phase: Phase 2
Intervention: Lapatinib
Conditions: Breast Cancer
Sponsor: Institute of Cancer Research, United Kingdom
Enrollment: 121
Locations: 1
Primary Endpoint: Changes in Ki67 after short term treatment with lapatinib.
Status: Completed
Last Updated: 13 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

To provide an in vivo measure of the activity of lapatinib. To assess the antiproliferative effects of lapatinib in breast cancer, ie how much lapatinib slows down the growth of cancer cells by measuring K167 (a marker of proliferation) in breast tumours before and after a short treatment with lapatinib.

Detailed Description

Randomised multi centre double blind pre-surgical study in women with a histological diagnosis of breast cancer by core biopsy.

Registry

clinicaltrials.gov

Start Date

June 2007

End Date

August 2011

Last Updated

13 years ago

Study Type

Interventional

Study Design

Single Group

Sex

Female

Investigators

Sponsor

Institute of Cancer Research, United Kingdom

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patients must have a histological or cytologic diagnosis of primary breast cancer with a tumour size adequate for multiple core biopsies Informed signed consent Scheduled for primary surgery Expected to be compliant for duration of study Age\<80 ECOG performance status 0-2 (Karnofsky \>60%) Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram or MUGA scan Eligibility of patients receiving medications known to affect, or with the potential to affect the activity or pharmacokinetics of lapatinib will be determined following review by the Trial Coordinator The effects if lapatinib on the developing fetus are unknown. For this reason, women of childbearing potential must agree to use adequate non-hormonal contraception for the duration of study participation.
•Able to swallow and retain oral medication.

Exclusion Criteria

•Patients with prior diagnosis of malignancy except in situ disease or basal cell carcinoma of the skin.
•Patients may be receiving any other investigational agents or receiving concurrent anticancer therapy. In addition, all herbal (alternative) medicines are excluded.
•Evidence of metastatic disease. Use of hormonal therapy such as oral contraceptives or hormonal replacement therapy within 4 weeks of study entry.
•Regular use of steroid hormones or other agents that could influence study endpoints History of allergic reactions attributed to compounds of similar chemical or biologic composition to GW
•Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/ social situations that would limit compliance with study requirements.

Arms & Interventions

Lapatinib

lapatinib oral 1500mg daily taken as 6 tablets as one dose 10-14 days presurgery

Intervention: Lapatinib

Lapatinib-Placebo

placebo comparator 6 tablets taken as one dose daily

Intervention: Lapatinib-Placebo

Outcomes

Primary Outcomes

Changes in Ki67 after short term treatment with lapatinib.

Time Frame: 11-14 days after treatment

Paired core samples taken at baseline and time of main surgery analysed for Ki67, TUNEL, HER2, EGFR, ER, PgR, pAkt,pERK \& stathmin

Secondary Outcomes

Assess how changes in Ki67 and apoptosis relate to molecular markers at baseline and after 2 weeks. These markers aer HER2, EGFR, p-HER2, p-EGFR, p-ERK1/2, pAKT, ER, PR, IGR-1R, cyclin D1, PTEN and TGF alpha. Further markers may be considered.(10-14 days after treatment)