E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary breast cancer hormone-sensitive in postmenopausal women |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10057654 |
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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 estimate the percentage of clinical objective responses cOR complete plus partial, measured by USG in the breast |
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E.2.2 | Secondary objectives of the trial |
- To estimate the percentage of pathological complete responses pCR in the breast and axillary nodes - To estimate the percentage of conservative surgery - To assess the safety profile of the combination of hormonal treatment plus lapatinib - To evaluate the time to treatment failure from start of primary therapy - To evaluate the percentage of inhibition of intermediate and final biomarkers of the proliferative and the apoptosis pathways induced by the hormonal treatment plus lapatinib or placebo - To evaluate the correlation between tumor gene expression at diagnosis and pathological response in the two treatment arms. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
- Histologically confirmed infiltrating primary breast cancer of 2.0 cm in largest clinical diameter - ER and/or PgR positive cancer 10 of positive cancer cell assessed by IHC - Postmenopausal status, defined by at least one of the following 61619; 60 years of age 60 years of age and amenorrheic for 61619; 12 months prior to day 1 60 years of age and amenorrheic for 12 months prior to day, or without a uterus luteinizing hormone LH and follicle stimulating hormone FSH values within postmenopausal range Prior bilateral oophorectomy Prior radiation castration with amenorrhea for at least 6 months - HER2 negative tumors IHC 0-2 , or FISH negative - Availability of tumor tissue suitable for biological and molecular examination before starting primary treatment - Age over 18 years - ECOG PS 0-1 - Normal organ and marrow function as defined below leukocytes 61472;3000/ 61549;L absolute neutrophil count 61472;1,500/ 61549;L platelets 61472;100,000/ 61549;L total bilirubin within normal institutional limits AST SGOT /ALT SGPT 2.5 X institutional upper limit of normal Creatinine within normal institutional limits - Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram or MUGA scan. - Eligibility of patients receiving medications or substances known to affect, or with the potential to affect the activity or pharmacokinetics of lapatinib will be determined following review of their use by the Principal Investigator. A list of medications and substances known or with the potential to interact with CYP450 isoenzymes is provided in Section 3.7.4.2 Other concomitant treatments. - Ability to understand and the willingness to sign a written informed consent document. - Ability to swallow and retain oral medication. |
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E.4 | Principal exclusion criteria |
- Stage IIIB, IIIC, and inflammatory breast cancer - Stage IV breast cancer - Contraindication to the treatment with letrozole - Prior treatment with chemotherapy, endocrine therapy or radiotherapy. Prior treatment with EGFR targeting therapies - Treatment with any other investigational agents, or with all herbal alternative medicines - History of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib - 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 - HIV-positive patients receiving combination anti-retroviral therapy - GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease e.g., Crohn s, ulcerative colitis - Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors See section 3.7.4.2 Other concomitant treatments |
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E.5 End points |
E.5.1 | Primary end point(s) |
percentage of clinical objective responses cOR complete plus partial, measured by USG |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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 | 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) | 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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |