E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057654 |
E.1.2 | Term | Breast cancer female |
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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 objectives of the study are represented by the evaluation of the safety and efficacy of the drug through the evaluation of the following parameters:
� reduced loss of bone mineral density (BMD or bone mass density); � assessing the occurrence of skeletal events (SRE) (pathological fractures, spinal compression, radiotherapy to the skeleton and use of radioisotopes, orthopedic surgery, amendment of analgesic therapy for pain OSEE) during the treatment period; � Time to first SRE; � Time to onset of each type of SRE; � reduction of skeletal morbidity rate ie number of SREs / year (calculated on the basis of occurrence of total and vertebral pathological fractures, radiotherapy, surgery, orthopedic, spinal compression, hypercalcemia of malignancy); � toxicity of the treatment; |
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E.2.2 | Secondary objectives of the trial |
levels`s changes of laboratory parameters (factors neoangiogenetici, proinflammatory cytokines, markers of bone resorption); � Changing the quality of life; � changes dell`ECOG PS; � overall survival; � Time to progression of bone cancer (onset of bone metastases); � Time to progression of neoplasia visceral (appearance of visceral metastases). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
age = or> 18 -75 aa; � ECOG PS 0-2; � diagnosis of breast cancer histologically confirmed; � stage of disease (stage I-III; any grading); � patients with malignant breast cancer with overt osteoporosis in adjuvant setting, already under loco-regional therapy (surgery + / - radiotherapy) and adjuvant chemotherapy (if indicated) at high risk of skeletal events (pathological fractures, spinal compression, radiation at skeleton and use of radioisotopes, orthopedic surgery, modification of analgesic therapy for pain OSEE); � osteoporosis, defined according to T score = or <-2.5 and the algorithm FRAXA; � positivity of breast cancer for estrogen-progestine receptors (ER + and / or PG +); � premenopausal patients in the adjuvant hormonal treatment for the underlying disease with tamoxifen + / - LHRH analogues; � postmenopausal patients adjuvant hormonal treatment for the underlying disease with aromatase inhibitors (letrozole, exemestane dell`anastrozolo except that on the basis of published scientific work is the AI which is associated with the highest risk of skeletal events determine Related to loss of bone mass); � written informed consent for participation in the study. |
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E.4 | Principal exclusion criteria |
pregnancy and lactation; � hypocalcemia; � impaired renal function with creatinine> 1.4 mg / dl at baseline; � Concomitant use of nephrotoxic drugs certainly; � Prior treatment with zoledronic acid or in progress; � documented hypersensitivity to bisphosphonates; � presence of serious diseases osteoarticular; � presence of severe dental disease; � previous history of malignancies other than breast cancer, excluding basalioma skin and carcinoma in situ of the cervix. |
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E.5 End points |
E.5.1 | Primary end point(s) |
reduced loss of bone mineral density (BMD or bone mass density); � assessing the occurrence of skeletal events (SRE) (pathological fractures, spinal compression, radiotherapy to the skeleton and use of radioisotopes, orthopedic surgery, amendment of analgesic therapy for pain OSEE) during the treatment period; � Time to first SRE; � Time to onset of each type of SRE; � reduction of skeletal morbidity rate ie number of SREs / year (calculated on the basis of occurrence of total and vertebral pathological fractures, radiotherapy, surgery, orthopedic, spinal compression, hypercalcemia of malignancy); � toxicity of the 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 | 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 | 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 | 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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | Information not present in EudraCT |
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
| |
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |