E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HER-2 positive primary breast cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10065430 |
E.1.2 | Term | HER-2 positive breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 whether pre-operative treatment of HER2 positive breast cancer patients with anti HER2 therapy increases cell death and/or decreases proliferation
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E.2.2 | Secondary objectives of the trial |
To identify indicators (molecular markers) of response to anti-HER2 therapy. At present, we can only look at markers in tumour tissue removed at surgery i.e. before any anti HER2 treatment. In EPHOS-B we aim to compare these markers using tissue taken before anti HER2 treatment with tissue taken again at surgery after 11 days (± 1 day) of treatment, to see which set of markers best predict a patient's future outcome.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Women aged ≥18 years. • HER2 positive (3+ on IHC or amplification proven by FISH*) operable invasive breast cancer diagnosed by core biopsy. • Planned surgery within one month of diagnosis. • Serum creatinine and bilirubin <2 times the upper limits of normal for the institution, or creatinine clearance >30mg/dL. (Marginally abnormal test results should be repeated). • ECOG performance status 0, 1, or 2 (Karnofsky ≥ 60%). • Non pregnant and non-lactating with no intention of pregnancy during study treatment. Women of childbearing potential must agree to use adequate non-hormonal contraception for the duration of the treatment phase of the study (adequate contraceptive measures include intra-uterine device, barrier method e.g. diaphragm and condoms used in conjunction with spermicidal jelly). Women of childbearing potential must have a negative blood serum pregnancy test within 28 days prior to randomisation). • Patients must be candidates for and willing to undergo adjuvant chemotherapy and trastuzumab post surgery. • Written informed consent obtained for trial and to donation of tissue and blood samples.
* Details of how FISH cases should be categorised are included the protocol.
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E.4 | Principal exclusion criteria |
• HER2 negative cancers and those with unknown HER2 status. • Inoperable breast cancer (T4 category) or suspicion of distant metastases. • Diagnosis of inflammatory breast cancer. • Clinical evidence of metastatic disease. • Prior herceptin therapy within the last 12 months or local (radiotherapy) cancer treatments. • Previous cancer at any other site that has been treated within the last 6 months (except previous basal cell carcinoma and cervical carcinoma in situ) • Have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones or stable chronic liver disease per investigator assessment). • Impaired gastro-intestinal function thought sufficient to reduce lapatinib absorption. • Contra-indicated to receive adjuvant chemotherapy and /or trastuzumab (ECOG >2). • Known immediate or delayed hypersensitivity, reaction to drugs chemically related to trastuzumab or lapatinib. • Other concomitant investigational agents or concurrent anti-cancer therapy. • Use of herbal (alternative) therapies within 2 weeks of study entry. (NB vitamin and / or mineral supplements are allowed).See Appendix 1 of the protocol. • If patients are taking any of the prohibited medication as listed in Appendix 1 of the protocol. • Regular use of systemic steroids or other agents that could influence study endpoints (inhaled steroids are allowed). • Any altered mental state that would preclude obtaining written informed consent. • Clinically significant cardiac abnormalities or uncontrolled hypertension. • Previous myocardial infarction, heart failure, or significant angina. Cardiac function should be assessed by physical examination, ECG, and baseline LVEF should be ≥55% as measured by echocardiography or MUGA. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints are preoperative changes in apoptosis and/or proliferation. The hypothesis is that there will be a significant increase in tumour apoptosis or a fall in tumour proliferation between baseline biopsy at diagnosis and surgery. |
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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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | 29 |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
E.8.7 | Trial has a data monitoring committee | Yes |
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
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For the purposes of Clinical Trial Authorisation (CTA) under the European Union Directive 2001/20/EC, the study is deemed to have ended 30 days after the last patient receives the last dose of perioperative trastuzumab or lapatinib. For all other purposes, the study end date is deemed to be the date of of last data capture.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 11 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |