E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage II-IIIA operable breast cancer, HER2 positive and hormone receptor-positive, previously untreated |
pazienti in postmenopausa con diagnosi di carcinoma mammario HER2 positivo e recettori ormonali positivi, in stadio clinico II-IIIA, non precedentemente trattato |
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E.1.1.1 | Medical condition in easily understood language |
Stage II-IIIA operable breast cancer, HER2 positive and hormone receptor-positive, previously untreated |
pazienti in postmenopausa con diagnosi di carcinoma mammario HER2 positivo e recettori ormonali positivi, in stadio clinico II-IIIA, non precedentemente trattato |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10072740 |
E.1.2 | Term | Locally advanced breast cancer |
E.1.2 | System Organ Class | 100000004864 |
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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 evaluate the rate of pathologic complete response (pCR), as defined as complete disappearance of invasive tumor in breast and axillary nodes |
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E.2.2 | Secondary objectives of the trial |
- To estimate the percentage of clinical objective responses (cOR) (complete plus partial) in the breast, as assessed by ultrasonography (US) - To estimate the percentage of breast conservative surgery - To evaluate the safety profile - Correlative biomarker analyses
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria: Patients may be included in the study only if they met all the following criteria - female patients with primary diagnosis of infiltrating breast cancer - HR positivity (ER ≥ 10% and/or PgR ≥10%) and HER2 positivity (IHC 3+ or FISH/CISH amplification) as assessed by local laboratory - Stage II-IIIA - age >18 yrs - ECOG Performance Status 0-1 - Postmenopausal status, defined by at least one of the following: 60 years of age; < 60 years of age and amenorrheic for >/=12 months prior to day 1 < 60 years of age, without a uterus, and 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 - Cardiac ejection fraction within the institutional range of normal (as measured by echocardiogram or MUGA scan). - Normal organ and marrow function as defined below: (leukocytes >=3000/mcL; absolute neutrophil count >=1,500/mcL; platelets >=100,000/mcL; total bilirubin within 1.25 x normal institutional limits (with the exception of Gilbert’s syndrome); AST (SGOT)/ALT(SGPT) within 1.25 x institutional upper limit of normal creatinine within normal institutional limits - Availability of tumor tissue suitable for biological and molecular examination before starting primary treatment - Ability to understand and the willingness to sign a written informed consent document.
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E.4 | Principal exclusion criteria |
Patients will be excluded from the study for any of the following reasons - Stage IIIB, IIIC, and inflammatory breast cancer - Stage IV breast cancer - Prior treatment with chemotherapy, endocrine therapy or radiotherapy. Prior treatment with HER2 targeting therapies - LVEF below the ULN - Uncontrolled hypertension (systolic >150 mm Hg and/or diastolic >100 mm Hg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident (CVA)/stroke or myocardial infarction within 6 months prior to first study medication, unstable angina, congestive heart failure (CHF) of New York Heart Association (NYHA) grade II or higher, or serious cardiac arrhythmia requiring medication. - Received any investigational treatment within 4 weeks of study start. - Subjects with known infection with HIV, HBV, HCV - Known hypersensitivity to any of the study drugs or excipients. - Dyspnea at rest or other disease requiring continuous oxygen therapy. - Psychiatric illness/social situations that would limit compliance with study requirements - Subjects assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol
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E.5 End points |
E.5.1 | Primary end point(s) |
to evaluate the rate of pathologic complete response (pCR), as defined as complete disappearance of invasive tumor in breast and axillary nodes |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- To estimate the percentage of clinical objective responses (cOR) (complete plus partial) in the breast, as assessed by ultrasonography (US) - To estimate the percentage of breast conservative surgery - To evaluate the safety profile - Correlative biomarker analyses
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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 | No |
E.8.1.1 | Randomised | No |
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 | 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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 10 |
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 | 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
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |