E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
hormone-receptor-positive metastatic breast cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10055113 |
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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 |
The primary objective of this study is to compare the time to-progression (TTP) of therapy with Letrozole (arm A) with therapy with Letrozole in combination with standard chemotherapy (arm B). |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are
• the comparisons of arm A with arm B with respect to the primary endpoint TTP separately in the subgroups of patients with - measurable disease and non-measurable disease / bone metastases only at entry - visceral and non-visceral disease at entry. • the comparisons of arm A with arm B with respect to: - quality-of-life (QoL) results , - objective response rate (ORR), - time-to- treatment-failure (TTF) - safety - overall survival (OS).
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
- Postmenopausal women defined by at least one of the following criteria: • women >50 years: no spontaneous menses for at least 2 years • Any age: no spontaneous menses in the last 1 year with FSH, LH and estradiol levels in the postmenopausal range for the laboratory of reference • Any age: bilateral oophorectomy or castration via radiotherapy with amenorrhea lasting > 3 months. - Histological or cytological evidence of breast cancer. - Estrogen and/or progesterone receptors positive, according to the definition of the reference laboratory, evaluated on the primary tumor or on a metastasis. - Patients with documented measurable and/or non-measurable metastatic disease according to RECIST criteria; patients with bone metastases as only site of disease are also eligible. - Performance Status 0-2 (ECOG scale). - Life expectancy > 6 months. - Adequate bone marrow reserve as evaluated with peripheral pretreatment values of Hb >10 g/dL, WBC > 3500/uL, Platelets > 100.000 > L. - Adequate renal function (creatinine within the normal range for the institution). - Adequate liver function (bilirubin within the normal range and liver enzymes < 2.5 times the normal upper limit for the institution). - Written informed consent.
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E.4 | Principal exclusion criteria |
- Patients who according to the treating physician require chemotherapy. - Patients considered for curative surgery - Prior systemic antitumor therapy for metastatic breast cancer. - If an anthracycline containing chemotherapy is chosen: Prior application of anthracyclines during adjuvant chemotherapy to an extent that would compromise an adequate dosage in anthracycline containing chemotherapy as first-line treatment. - Systemic investigational drugs within the prior month. - Treatment with trastuzumab (Herceptin) containing regimens . - Prior use of aromatase inhibitors. - Patients receiving LHRH agonists/antagonists. - Known CNS metastases - Uncontrolled cardiac disease (i.e. severe hypertension, angina pectoris despite treatment, history of uncontrolled atrial or ventricular arrhythmia, myocardial infarction in the prior six months). - Other concurrent or previous malignancies within the last 5 years except for contralateral breast carcinoma, cone biopsied in-situ carcinoma of the cervix uteri or adequately treated basal or squamous cell carcinoma of the skin. - History of non compliance to medical regimens and patients who are considered unreliable. - Any contraindication for the selected chemotherapy regimen.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary evaluation of the primary endpoint TTP will be the comparison of - chemotherapy given in combination with Letrozole (Arm B) versus Letrozole single agent (Arm A); This comparisons will be adjusted statistically for randomizing center, measurability/non-measurability of disease, and presence/absence of visceral lesions This designated primary confirmative evaluation of this study comprises a one-sided statistical hypothesis test on the significance level of 5% .The primary endpoint, TTP, will be statistically analyzed by the Cox proportional hazards regression method. The hazard ratio (HR), 95% confidence interval (CI) for the HR, and Chi-squared P-value derived from the Wald statistic will be reported. Median TTP with its 95% confidence interval and the 2 year survival rate with its 95% confidence interval will be estimated by the Kaplan-Meier product-limit method separately for each arm
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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 | 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) | 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
| 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 | 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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The trial will be closed 2 years after the last subject has been entered into the clinical trial. The expected end of recruitment is December 2007, leading to an expected end date of December 2009. All patient will be in an observational F/U until death or until the end of 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 | 4 |
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 | 4 |