E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-rhabdomyosarcoma soft tissue sarcoma.
The so called “non-rhabdomyosarcoma” soft tissue sarcomas (NRSTS) account for about 3-4% of paediatric cancers and constitute a very heterogeneous group of tumours with a variety of histotypes with different origins, biology and natural history, some of which are more common in adults. |
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MedDRA Classification |
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 |
First objective of the study is to make uniform the treatment of NRSTS patients in Europe. Patients will be treated with a risk-adapted multidisciplinary treatment approach.
In particular, the protocol aims to investigate, as main objectives:
• the survival rates (event-free survival EFS and overall survival OS) and the pattern of treatment failure in patients with synovial sarcoma and adult-type sarcomas • the role of an ifosfamide-doxorubicin regimen in improving the response rate in patients with unresectable (measurable disease) synovial sarcoma and adult-type sarcomas
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E.2.2 | Secondary objectives of the trial |
Secondary objectives will be:
• the prospective evaluation of clinical/pathological prognostic factors, in particular: a) the radiological and pathological response to neo-adjuvant treatment, b) the tumour grade, assessed according to the POG and the FNCLCC, and to the new prospective EpSSG grading system • the impact of the omission of adjuvant chemotherapy in patients with low-risk synovial sarcoma (IRS group I, tumour smaller than 5 cm) • the role of adjuvant chemotherapy in IRS group I-II, G3, size > 5 cm adult-type STS patients in improving the metastases-free survival (MRS) and the OS
Moreover, the study aims to improve the biological studies and samples collection of these malignancies.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Eligibility criteria for the prospective non-randomized historically-controlled trial are the following:
A pathologically proven diagnosis of synovial sarcoma and adult-type soft tissue sarcomas
No evidence of metastatic lesions
Age less than 21 years (20 years and 364 days) of age
No previous treatment except for primary surgery
For patients who require adjuvant chemotherapy according to protocol guidelines, no more than a 8 week-interval between the diagnostic surgical approach and the start of chemotherapy
For patients who require adjuvant chemotherapy according to protocol guidelines, no pre-existing illness preventing treatment (in particular renal function must be equivalent to grade 0-1 nephrotoxicity, no prior history of cardiac disease and normal shortening fraction [> 28%] and ejection fraction [> 47%])
No previous malignancy Patients with post-irradiation soft part sarcomas could be registered and treated according to the protocol guidelines, but they will be analysed separately
Diagnostic material available for pathology review
Available for long term follow up through the treatment centre
Written informed consent for treatment available.
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E.4 | Principal exclusion criteria |
Absence of any of the above |
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E.5 End points |
E.5.1 | Primary end point(s) |
The objectives of the study are: • Event free survival (EFS), measured as time from histological diagnosis (first surgical approach – biopsy or resection – that leads to histological diagnosis) up to an event. Event is defined as: death for all reasons, progression of a residual tumour, relapse following previous complete remission, appearance of a new tumour. Patients without an event at the end of the study or lost to follow up will be censored at the date of last observation. • Local relapse free survival (LRFS), measured as time from histological diagnosis up to local progression or local relapse. Patients without local failure at the end of the study or lost to follow up will be censored at the date of last observation. • Metastases free survival (MFS), measured as time from histological diagnosis up to appearance of metastasis. Patients without metastasis at the end of the study or lost to follow up will be censored at the date of last observation. • Overall survival (OS), measured as time from histological diagnosis up to death for all reasons. Patients still alive at the end of the study or lost to follow up will be censored at the date of last observation. • Response rate in according to classification criteria reported in chapter 16. Complete response, very good partial response, partial response, minor partial response and stable disease will be considered responses in this study.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | 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.8.5 | 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 | 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 | 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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Accrual of 250 patients European wide - expected within 5 years, then a 3 year follow-up period. |
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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 | 5 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |