Clinical trial NCT00299286: Short-term Presurgical Study to Assess Molecular Predictors of Lapatinib's Effects in Primary Breast Cancer
Official title: A Double Blind Short-Term Presurgical Study Assessing the Molecular Antiproliferative Predictors of Lapatinib's Effects in Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Ki67
Molecular
antiproliferative
Lead sponsor: Institute of Cancer Research, United Kingdom
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2006-03-06
Enrollment: 121
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: Changes in Ki67 after short term treatment with lapatinib.
timeFrame: 11-14 days after treatment
Secondary outcomes:
measure: 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.
timeFrame: 10-14 days after treatment
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust
Study officials:
affiliation: Royal Marsden NHS Foundation Trust
name: Professor Ian Smith
role: PRINCIPAL_INVESTIGATOR
References: