E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced or metastatic STS patients untreated or previously treated with one or more prior systemic regimen. |
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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 | HLGT |
E.1.2 | Classification code | 10041299 |
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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 |
To evaluate the effect on progression-free survival (PFS) of two NGR-hTNF doses administered either as single agent or in combination with doxorubicin |
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E.2.2 | Secondary objectives of the trial |
- To determine the safety/toxicity profile of two NGR-hTNF doses given either as single agent or in combination with doxorubicin. - To evaluate the effect on response rate (according to RECIST criteria), disease control rate, and overall survival. - To evaluate the effect on metabolic response rate (as measured by FDG-PET). - To exploratively evaluate tumor response by centralized review of changes in tumor density on CT scan and/or perfusion/diffusion MRI |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients ≥18 years - Histologically-proven, locally advanced, or metastatic STS (excluding extraosseus Ewing sarcoma) - Patients not amenable to surgery, radiotherapy, or combined-modality therapy with curative intent - Patients untreated or previously treated with one or more systemic regimen - ECOG Performance status 0-2 (Appendix A) - At least one untreated (not previously irradiated) target lesion that could be measured in one dimension, according to RECIST criteria - A life expectancy of 12 weeks or more - Adequate baseline bone marrow, hepatic and renal function, defined as follows: Neutrophils > 1.5 x 109/L and platelets > 100 x 109/L; Bilirubin < 1.5 x ULN; AST and/or ALT < 2.5 x ULN in absence of liver metastasis or < 5 x ULN in presence of liver metastasis; Serum creatinine < 1.5 x ULN; Creatinine clearance (estimated according to Cockcroft-Gault formula, Appendix A) ≥ 50 ml/min - Patients may have had prior treatment providing the following conditions are met before treatment start: - Surgery and radiation therapy: wash-out period of 14 days; Systemic therapy: wash-out period of 21 days - Patients must give written informed consent |
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E.4 | Principal exclusion criteria |
- Patients may not receive any other investigational agents while on study - Patients with myocardial infarction within the last six months, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication - LVEF < 55% (only for patients candidate for doxorubicin treatment) - Uncontrolled hypertension - Prolonged QTc interval (congenital or acquired) > 450 ms - History or evidence upon physical examination of CNS disease unless adequately treated (e.g., primary brain tumour, any brain metastasis, seizure not controlled with standard medical therapy) or history of stroke - Patients with active or uncontrolled systemic disease/infections or with serious illness or medical conditions, which is incompatible with the protocol - Known hypersensitivity/allergic reaction to human albumin preparations or to any of the excipients - Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol - Pregnancy or lactation. Patients - both males and females - with reproductive potential (i.e. menopausal for less than 1-year and not surgically sterilized) must practice effective contraceptive measures throughout the study. Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary study endpoint is the 3-month PFS rate, with tumor restaging performed according to RECIST criteria |
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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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
- same IMP used at different dosage |
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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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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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Per conclusione dello studio si intende la data della visita di chiusura dell`ultimo centro, in quanto solo con la visita di chiusura tutti i dati saranno stati validati e i documenti dello studio riverificati |
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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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |