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

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Institute of Cancer Research, United Kingdom
ClinicalTrials.gov Identifier:
NCT00299286
First received: March 3, 2006
Last updated: August 3, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: Lapatinib
Drug: Lapatinib-Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double Blind Short-Term Presurgical Study Assessing the Molecular Antiproliferative Predictors of Lapatinib's Effects in Breast Cancer

Resource links provided by NLM:


Further study details as provided by Institute of Cancer Research, United Kingdom:

Primary Outcome Measures:
  • Changes in Ki67 after short term treatment with lapatinib. [ Time Frame: 11-14 days after treatment ] [ Designated as safety issue: No ]
    Paired core samples taken at baseline and time of main surgery analysed for Ki67, TUNEL, HER2, EGFR, ER, PgR, pAkt,pERK & stathmin


Secondary Outcome Measures:
  • 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. [ Time Frame: 10-14 days after treatment ] [ Designated as safety issue: No ]

Enrollment: 121
Study Start Date: June 2007
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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.


Detailed Description:

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

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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 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.

  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: NCT00299286

Locations
United Kingdom
Royal Marsden NHS Foundation Trust
London, United Kingdom
Sponsors and Collaborators
Institute of Cancer Research, United Kingdom
GlaxoSmithKline
Investigators
Principal Investigator: Professor Ian Smith Royal Marsden NHS Foundation Trust
  More Information

No publications provided

Responsible Party: Institute of Cancer Research, United Kingdom
ClinicalTrials.gov Identifier: NCT00299286     History of Changes
Other Study ID Numbers: CCR2737
Study First Received: March 3, 2006
Last Updated: August 3, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Institute of Cancer Research, United Kingdom:
Ki67
Molecular
antiproliferative

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Lapatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 20, 2014