E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced or metastatic Soft-tissue sarcoma in patients untreated or previously treated with one or more prior systemic
regimen. |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | HLGT |
E.1.2 | Classification code | 10041299 |
E.1.2 | Term | Soft tissue sarcomas |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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. |
|
E.2.2 | Secondary objectives of the trial |
To determine the safety/toxicity profile of two NGRhTNF
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. |
|
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 10^9/L and platelets > 100 x 10^9/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 |
|
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 Progression-Free Survival of 2 doses of NGR-hTNF administrated either alone or in combination with doxorubicin. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- On an ongoing basis: to determine the safety profile of two doses of NGR-hTNF given either alone or in combination with doxorubicin.
- Every 12 weeks after progression disease:to evaluate overall survival
Approximately every 6 weeks:
- 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.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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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, alone or in combination with doxorubicin |
|
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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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The study completion is defined as the date of the close-out visit of the last center, on the condition that all the data have been validated and reassessed the study documents |
|
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 | 4 |
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 | 6 |