E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Estrogen receptor positive locally advanced or metastatic breast cancer in postmenopausal women |
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E.1.1.1 | Medical condition in easily understood language |
Estrogen receptor positive locally advanced or metastatic breast cancer in postmenopausal women |
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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 | 10070575 |
E.1.2 | Term | Estrogen receptor positive 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 safety of everolimus (RAD001) in postmenopausal women with hormone receptor positive locally advanced or metastatic breast cancer after recurrence or progression following NSAIs treatment |
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E.2.2 | Secondary objectives of the trial |
- to evaluate adverse events grade 3 and 4 in the routine practice
- to explore the tolerability of the concomitant treatment of zoledronic acid RTU (Ready To Use) formulation in patients who will receive this treatment according to the clinical practice |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adult women (≥ 18 years of age) with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy, whose disease recurred or progressed following a NSAI treatment.
Letrozole or anastrozole do not have to be last treatment prior to study enrollment.
2. Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer and/or progesterone receptor-positive (PgR+)
3. Postmenopausal women. Postmenopausal status is defined either by:
• Age ≥ 55 years and one year or more of amenorrhea
• Age < 55 years and one year or more of amenorrhea, with an estradiol assay < 20 pg/ml
• Surgical menopause with bilateral oophorectomy
4. Adequate bone marrow and coagulation function as shown by:
• Absolute neutrophil count (ANC) ≥ 1.5 109/L
• Platelets ≥ 100 ×109/L
• Hemoglobin (Hgb) ≥ 9.0 g/dL
• INR ≤ 2
5. Adequate liver function as shown by:
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 ULN (or ≤ 5 if hepatic metastases are present)
• Total serum bilirubin ≤ 1.5 × ULN (≤ 3 × ULN for patients known to have Gilbert Syndrome)
6. Adequate renal function as shown by:
• Serum creatinine ≤ 1.5 × ULN
7. Fasting serum cholesterol ≤ 300 mg/dl or 7.75 mmol/L and fasting triglycerides ≤ 2.5 × ULN. In case one or both of these thresholds are exceeded, the patient can only be included after initiation of statin therapy or other lipid lowering drugs (eg fibrates), and when the above mentioned values have been achieved
8. Written informed consent obtained before any screening procedure and according to local guidelines
Other protocol defined inclusion criteria may apply |
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E.4 | Principal exclusion criteria |
1. HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive).
2. Pre-menopausal, pregnant, lactating women
3. Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin) or to their excipients.
4. Known hypersensitivity to exemestane, to the active substance or to any of the excipients.
5. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose galactose malabsorption.
6. Radiotherapy within four weeks prior to enrollment except in case of localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture which can then be completed within two weeks prior to enrollment. Patients must have recovered from radiotherapy toxicities prior to enrollment.
7. Currently receiving hormone replacement therapy, unless discontinued prior to enrollment.
8. Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use, at the time of study entry except in cases outlined below:
Prolonged systemic corticosteroid treatment during study, except for topical applications (e.g. rash),inhaled sprays (e.g. obstructive airways diseases), eye drops or local injections (e.g. intraarticular) should not be given. However, during the study:
• short duration (<2 weeks) of systemic corticosteroids is allowed (e.g. chronic obstructive pulmonary disease, anti-emetic) ;
• low doses of corticosteroids for brain metastasis treatment is allowed
9. Patients with symptomatic visceral disease in need of urgent disease control
10. Symptomatic brain or other CNS metastases.
Previously treated symptomatic brain metastases are allowed provided the patient is free of symptoms, prior radiotherapy for brain metastasis was more than four weeks before enrollment and the dose of corticosteroids is low and stable for at least two weeks prior to enrollment
Other protocol defined exclusion criteria may apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
frequency of adverse events and number of laboratory values that are new or worsening |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Adverse events: continuously, up to 28 days after last treatment
Laboratory values: continuously or as frequently as clinically indicated |
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E.5.2 | Secondary end point(s) |
- frequency of adverse events that is recorded as Grade 3 or 4 or as Serious Adverse Event
- frequency of adverse events of any grade in the group of patients who have received concomitant treatment with zoledronic acid RTU formulation, administered according to clinical practice |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Continuously, up to 28 days after the last treatment |
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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 | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 500 |
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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LPLV (last patient last visit) |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |