Short-term Presurgical Study to Assess Molecular Predictors of Lapatinib's Effects in Primary Breast Cancer (MAPLE)

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Lapatinib; Drug: Lapatinib-Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Royal Marsden NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 GW572016.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lapatinib; lapatinib oral 1500mg daily taken as 6 tablets as one dose 10-14 days presurgery	Drug: Lapatinib; In order for patients to take their study medication for 14 days only, treatment should commence on the 14th day prior to the day before scheduled surgery (i.e. if surgery is scheduled for the 15th of the month, tablets should be taken from the 1st to the 14th of that month). Lapatinib tablets are dispensed as 250mg tablets. Patients should be advised to take all 6 tablets at once as one dose (total daily dose 1500mg). Tablets should be taken on an empty stomach either one hour before or one hour after a meal at the same time each day and according to the instructions on the bottle.; Other Names: Tyverb
Placebo Comparator: Lapatinib-Placebo; placebo comparator 6 tablets taken as one dose daily	Drug: Lapatinib-Placebo; In order for patients to take their study medication for 14 days only, treatment should commence on the 14th day prior to the day before scheduled surgery (i.e. if surgery is scheduled for the 15th of the month, tablets should be taken from the 1st to the 14th of that month). Lapatinib-placebo tablets will be composed of lactose, cellulose, starch, magnesium stearate, and coated with Opadryl orange and look the same as the active treatment. The patients should take all 6 tablets at once as one dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Ki67 after short term treatment with lapatinib.	Paired core samples taken at baseline and time of main surgery analysed for Ki67, TUNEL, HER2, EGFR, ER, PgR, pAkt,pERK & stathmin	11-14 days after treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Institute of Cancer Research, United Kingdom
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Professor Ian Smith, Royal Marsden NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: March 3, 2006
• First Submitted That Met QC Criteria: March 3, 2006
• First Posted (Estimate): March 6, 2006

Study Record Updates

• Last Update Posted (Estimate): August 6, 2012
• Last Update Submitted That Met QC Criteria: August 3, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: Molecular; Ki67; antiproliferative
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Lapatinib
• Other Study ID Numbers: CCR2737