E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
This study will be a head to head comparison of letrozole versus anastrozole in the adjuvant treatment of high risk patients. Post-menopausal patients who recently have undergone their primary surgery for their breast cancer are targeted patient population. They must also have hormone positive disease and have lymph node positive disease. The primary surgery could have been a total mastectomy, lumpectomy or quadrantectomy for primary breast cancer. |
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MedDRA Classification |
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 compare the rate of disease free survival (DFS) at 5 years in postmenopausal women with hormone receptor and lymph node positive breast cancer randomized between letrozole and anastrozole. |
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E.2.2 | Secondary objectives of the trial |
• To compare the general safety between the two treatment arms. • To compare the two treatment groups in a descriptive manner with the other indicators of efficacy including overall survival, breast cancer specific survival, time to development of distant metastases and time to development of contra lateral breast cancer. • Compare percent change in BMD between the two arms • Compare the effects of treatment on serum lipid profiles in both treatment arms • Compare the incidence of clinical fractures between 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 |
• provision of written informed consent • undergone a total mastectomy, a lumpectomy, or a quadrantectomy for primary breast cancer. • the date of randomization must be no more than: • 4 weeks from completion of surgery or. • 4 weeks after completion of adjuvant chemotherapy. Note adjuvant radiation and endocrine therapy e.g. letrozole and anastrozole can be given at the same time as radiotherapy due to non-overlapping toxicity profile. • presence of node positive disease. • receptor-positive tumors, defined ER ≥10 fmol/mg cytosol protein; or ≥10% of the tumor cells positive by immunocytochemical evaluation. • postmenopausal whether induced by surgery, radiotherapy or chemotherapy, or by being naturally amenorrheic, for 1 year or more if younger than 50 and for 6 months if 50 or older. • postmenopausal levels of FSH/LH/E2 (follicle stimulating hormone, luteinizing hormone, estrogen) according to the definition of “postmenopausal range” for the laboratory involved. • WBC ≥ 3.0 x 109/L, granulocytes ≥ 1.5 X 109/L and platelets ≥ 100 x 109/L. • AST/SGOT or ALT/SGPT ≤ 3 times ULN. • serum creatinine ≤ 2 times ULN. |
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E.4 | Principal exclusion criteria |
• presence of metastatic disease. • concomitant or prior bilateral breast cancer. • previous or concomitant other (non-breast cancer) malignancy within the previous 5 years. • presence of other non-malignant systemic diseases which may prevent prolonged follow-up. • if no history of previous coronary heart disease but has at least two other coronary heart disease risk factors: LDL ≥160 mg/dL OR if fewer than two other coronary heart disease risk factors: LDL ≥190 mg/dL. • total fasting cholesterol ≥ 240 mg/dL. • patients on lipid-lowering agents, diet, or other measures for hyperlipidemia at baseline. • progressed on neoadjuvant endocrine therapy • hormone replacement therapy (HRT) within 4 weeks before trial treatment was initiated. • adjuvant anti-estrogen therapy for more than 1 month immediately following surgery, radiotherapy and/or chemotherapy. • Breast cancer chemoprevention with anti-estrogens if less than 18 months between stopping and diagnosis of breast cancer. • Severe hepatic dysfunction defined as Child-Pugh grade C. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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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 | Information not present in EudraCT |
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 | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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
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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 | 7 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |