E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Breast Cancer with triple negative profile (ER-, PR-, HER2-),HER2 overexpressing tumors and BRCA1 or BRCA2 mutation carriers. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
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 |
Primary Objective: to determine the objective response rate by RECIST (Complete and Partial Response [CR + PR]) with trabectedin in patients with the following metastatic breast cancer subtypes: Group A: triple negative profile (ER-,PR-,HER-2-) Group B: human epidermal growth factor receptor-2 overexpressing tumors (HER-2+) Group C: familial BRCA1 or BRCA2 mutation carriers |
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E.2.2 | Secondary objectives of the trial |
To assess in each group Duration of response Progression-free survival Exploratory evaluation of changes in tumor volume (three dimensional analysis) and changes in tumoral radiological density Safety profile in this patient population Exploratory, hypothesis-generating pharmacogenomic analyses to correlate molecular parameters in patient samples with clinical outcomes (objective response and PFS) within and across patient strata. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1.PatientŽs written informed consent before any clinical trial-specific procedure. 2.Woman 18 years-of-age or older. 3.Histologically proven diagnosis of progressive metastatic breast cancer either in documented: Group A: triple negative phenotype [Estrogen Receptor, Progesterone Receptor and HER-2 negative status (surrogate of basal-like type)]. Patients will be eligible if they had received prior therapy with an anthracycline, a taxane and capecitabine, including adjuvant or neoadjuvant therapy, but no more than three prior chemotherapy regimens for metastatic disease. NOTE: re-treatment with the same regimen or its components after a progression-free interval of 6 months or longer will be considered a second regimen. Group B: HER-2 overexpressing breast cancer. Patients will be eligible if they have progressive metastatic disease following treatment with anthracyclines, taxanes and capecitabine, with trastuzumab or other HER-2 target agent , but no more than three prior chemotherapy regimens for metastatic disease are allowed. NOTE: re-treatment with the same regimen or its components after a progression-free interval of 6 months or longer will be considered as second regimen. Group C: Familial BRCA1 or BRCA2 mutation carriers. Patients will be eligible if they had received prior therapy with an anthracycline, a taxanes and capecitabine, including adjuvant or neoadjuvant therapy, without prior lines limitation. 4.Measurable disease as defined in the Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines. If the only indicator lesion is in a previously irradiated area, the recurrence must be biopsy proven. 5.Patients with bone metastases currently receiving biphosphonates for palliation will be eligible if other sites of measurable disease are present. 6.Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1. 7.Hematologic variables: Hemoglobin more than or equal to 9 g/dL Absolute neutrophil count (ANC) more than or equal to 1,500/µL, and Platelet count more than or equal to 100,000/µL. 8. Serum creatinine less than or equal to 1.5 mg/dL or creatinine clearance more than or equal to 30 mL/min 9. Creatinine phosphokinase (CPK) less than or equal to 2.5 ULN. 10. Hepatic function variables Total bilirubin less than or equal to ULN. Total alkaline phosphatase less than or equal to 2.5 ULN, or if > 2.5 ULN consider alkaline phosphatase liver fraction or GGT or 5 nucleotidase must be less than or equal to ULN, if the elevation could be osseous in origin. AST (serum aspartate transaminase [SGOT]) and ALT (serum alanine transaminase [SGPT]) must be less than or equal to 2.5 x ULN. 11 Albumin more than or equal to 25 g/l. 12. Adequately recovered from the acute toxicity of any prior treatment. |
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E.4 | Principal exclusion criteria |
1.Prior exposure to trabectedin. 2.Known hypersensitivity to any of the components of the trabectedin i.v. formulation or dexamethasone. 3.More than three prior chemotherapy regimens for metastatic disease for group A and B. NOTE:re-treatment with the same regimen or its components after a progression-free interval of 6 months or more is considered a second regimen. 4.Pregnant or lactating women or any women of childbearing potential who is not employing adequate contraception. Acceptable methods of contraception include; IUD, and double barrier (condom with a contraceptive sponge or contraceptive suppository). Use of hormonal contraception is not acceptable during this clinical trial. 5.Less than 4 weeks from radiation therapy or last dose of hormonal therapy, biological therapy, therapy with any investigational agent, or chemotherapy (6 weeks if a nitrosurea or mitomycin C). 6.History of another neoplastic disease (except basal cell carcinoma or cervical carcinoma in situ adequately treated) unless in remission for 5 years or longer. 7.Known clinically relevant CNS metastases. 8.Other serious illnesses, such as: Congestive heart failure or angina pectoris; myocardial infarction within 1 year before enrollment; uncontrolled arterial hypertension or arrhythmias Psychiatric disorder that prevents compliance with protocol Active viral hepatitis; or chronic liver disease Active infection Any other unstable medical conditions ble during this clinical trial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
L'efficacia verra' valutata stabilendo la risposta obiettiva e PFS. La malattia misurabile e i criteri di risposta utilizzati in questo protocollo sono stati definiti dalle linee guide RECIST. |
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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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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
| 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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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 | 7 |
E.8.9.1 | In the Member State concerned days | |
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 | 7 |