Randomised Controlled Trial of Lapatinib (A Her1/2 Tyrosine Kinase Inhibitor) on Epithelial Proliferation and Apoptosis in Ductal Cancer in Situ. - Pre-operative study of Lapatanib in DCIS

Phase 1

• Conditions: Women with a core biopsy diagnosis of histologically proven Her2 positive DCIS (or DCIS and invasive cancer). Women undergoing re-excision of DCIS will be eligible provided residual DCIS is present in the re-excision specimen.; MedDRA version: 9.1Level: LLTClassification code 10065430Term: HER-2 positive breast cancer

• Registration Number: EUCTR2006-006619-64-GB
• Lead Sponsor: niversity Hospital of South Manchester NHS Foundation Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2008-02-22
• Last Update Posted: 16 December 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 80

Inclusion Criteria

• Women with a core biopsy diagnosis of histologically proven Her2 positive DCIS or DCIS and invasive cancer.
• All patients must give written informed consent for the use of core and excision biopsy prior to entering the trial.
• Patients will undergo definitive surgical excision of their DCIS plus or minus invasive cancer within 14-21 days of the core biopsy.
• Women undergoing re-excision of DCIS will be eligible provided residual DCIS is present in the re-excision specimen and 14-21 days of treatment are given between diagnostic biopsy and therapeutic excision.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

• Patients not undergoing definitive surgery for DCIS
• Her2 negative DCIS
• Patients unable to give informed consent
• Primary chemotherapy as a neoadjuvant treatment
• Patients with any serious systemic disease which precludes the use of Lapatinib or tyrosine kinase inhibitors
• Patients using non-steroidal anti-inflammatory drugs
• Allergy or aspirin allergy
• Patients will not be on Lapatanib or a tyrosine kinase inhibitor prior to core biopsy. No previous invasive or in situ cancer will have been diagnosed within the same ipsilateral breast prior to diagnosis.
(a) Cardiovascular disease e.g. ischaemic heart disease
(b) Previous stroke/transient ischaemic attack or cerebrovascular disease
(c) Uncontrolled hypertension
• Previous chemotherapy or radiotherapy in the past 12 months prior to study entry.
• Pregnancy.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the short term anti-proliferative effect and apoptosis inducing effect of Lapatinib, a Her1/Her2 tyrosine kinase inhibitor on epithelial proliferation (as adjudged by Ki67) and apoptosis.;Secondary Objective: To determine the effect of Lapatinib compared with placebo on apoptosis, survivin and progesterone receptor staining in histologically diagnosed Her2 positive DCIS. <br><br>To determine the effect of Lapatinib on epithelial proliferation, apoptosis, survivin and progesterone receptor expression in normal breast tissue from the surrounding breast around a mastectomy or wide local excision after surgical excision. <br>;Primary end point(s): A reduction in DCIS epithelial proliferation as measured by Ki67 labelling index immunohistochemistry or an increase in apoptosis as measured by TUNEL assays (and Caspase3 expression). Ki67 and apoptosis markers will be measured as a primary endpoint in lapatanib treated Her2 positive DCIS compared to placebo.