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

NCT00299286 | Completed Phase 2 DMC

• 1 other identifier: CCR2737
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Keywords

Ki67; Molecular; antiproliferative

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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

Study Arms (2)

Lapatinib

EXPERIMENTAL

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

Drug: Lapatinib

Lapatinib-Placebo

PLACEBO COMPARATOR

placebo comparator 6 tablets taken as one dose daily

Drug: Lapatinib-Placebo

Interventions

Lapatinib DRUG

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.

Also known as: Tyverb

Lapatinib

Lapatinib-Placebo DRUG

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.

Lapatinib-Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institute of Cancer Research, United Kingdom: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Royal Marsden NHS Foundation Trust

London, United Kingdom

Location

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

• Professor Ian Smith

  Royal Marsden NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2006
• First Posted: March 6, 2006
• Study Start: June 1, 2007
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: August 6, 2012

Record last verified: 2012-08

Locations

GB (1)