E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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 Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065430 |
E.1.2 | Term | HER-2 positive breast cancer |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
|
E.2.2 | Secondary objectives of the trial |
To determine the effect of Lapatinib compared with placebo on apoptosis, survivin and progesterone receptor staining in histologically diagnosed Her2 positive DCIS.
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.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
|
|
E.4 | Principal 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.
|
|
E.5 End points |
E.5.1 | 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. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |