E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Leiomiosarcomi uterini metastatici o in progressione locale |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046799 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary objective will be to assess the clinical benefit rate (defined as 6-month progression free rate) with T in patients with locally relapsed/metastatic uterine leiomyosarcoma pretreated with anthracycline � ifosfamide and/or gemcitabine � docetaxel. For the subgroup population pretreated only with anthracycline � ifosfamide the patients enrolled in the arm B will serve as a parallel internal control. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives will be to assess the response rate, the progression free survival, the overall survival, and the toxicity profile. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
FARMACOCINETICA/FARMACODINAMICA: Versione:1.1 Data:2009/08/04 Titolo:Espressione di BRCA1, ERCC1, XPG e beneficio clinico Obiettivi:La revisione anatomo-patologica centralizzata permettera` di valutare i fattori predittivi morfologici (necrosi, atipie cellulare e conta mitotica) e biologici ( ER, pgR, p53 , markers del ciclo cellulare [mdm2, p16 and p21], WT1, cKIT, EGFR and VEGFR) del beneficio clinico. Saranno condotti studi nelle pazienti arruolate sia nel braccio A che nel braccio B per valutare lespressione di BRCA1, ERCC1 e XPG attraverso lestrazione dellmRNA dai campioni tumorali paraffinati. I livelli di espressione proteica di BRCA1, ERCC1 e XPG saranno valutati con metodi immunoistochimici.
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E.3 | Principal inclusion criteria |
1)Histologically proven uterine leiomyosarcoma. 2)Persistent or locally relapsed and/or metastatic disease. 3)At least one previous systemic treatment with an anthracycline � ifosfamide or gemcitabine � docetaxel. 4)Measurable disease, as defined by RECIST criteria. 5)ECOG PS <=2. 6)Age >= 18 years. 7)A minimum of 3 weeks since prior tumor directed therapy 8)Recovery from toxic effects of prior therapies to NCI CTC Grade 1 or lower. 9)Adequate haematological function. 10)Adequate renal function. 11)Adequate liver function. 12)Signed informed consent. |
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E.4 | Principal exclusion criteria |
1)Prior exposure to T. 2)Peripheral neuropathy, Grade 2 or higher. 3)History of other malignancies (except basal cell carcinoma or cervical carcinoma in situ, adequately treated), unless in remission from 5 years or more and judged of negligible potential of relapse. 4)Known CNS metastases. 5)Active viral hepatitis or chronic liver disease. 6)Unstable cardiac condition, including congestive heart failure or angina pectoris, myocardial infarction within one year before enrolment, uncontrolled arterial hypertension or arrhythmias. 7)Active major infection. 8)Other serious concomitant illnesses. |
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E.5 End points |
E.5.1 | Primary end point(s) |
clinical benefit rate (defined as 6-month progression free rate) |
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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 | No |
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 | 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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 20 |
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
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Raggiungimento della numerosita` campionaria prevista; se si osserveranno piu` di 22 "successi" nel braccio sperimentale (trabectedina) si potra` comunque valutare se procedere ad uno studio di fase III comparativo |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |