CWS-2007-HR

Localised high-risk rhabdomyosarcoma and localised RMS-like Soft Tissue Sarcoma in remission (according to the CWS-2007-HR definition)

Randomised, open-label, multicentric, prospective, non-blinded, phase-III-trial for localised high-risk Soft Tissue Sarcoma in children, adolescents and young adults <21 years

Based on the model of SoTiSar the CWS-2007-HR is the first Phase-III-trial that starts on 01.07.2009. The Cooperative-Soft-Tissue-Sarcoma trial CWS-2007-HR is a multinational, multicentric, randomised, open-label, prospective, non-blinded, phase-IIIstudy
for localised high-risk rhadbomyosarcoma and localised high-risk RMS-like STS in children, adolescents, and young adults <21 years to improve treatment outcome.

The object of the inquiry is an ambulant oral maintenance chemotherapy with an oral medication over six month. This oral therapy with Etoposide, Idarubicin and Trofosfamide will be randomized against the standard-arm, which is finished after the end of the intensive chemotherapy (no maintenance therapy).
• Arm A: no further therapy
or
• Arm B: 25 weeks of oral maintenace therapy with 8 courses O-TIE

The primary objective is:
1.To investigate whether the addition of oral maintenance chemotherapy with O-TIE (Etoposide, Idarubicin, Trofosfamide) for 6 months improves the event free survival (EFS) in patients with localised high-risk RMS and RMS-like Soft Tissue Sarcoma.

The secondary objectives are:
2. To investigate, whether the additon of oral maintenance therapy (O-TIE) for 6 months after multimodal standard therapy have impact on following outcomes: overall survival (OS), short-term toxicity and late effects in patients with localised high-risk RMS and RMS-like STS
3. To reassess the European consensus on risk-stratification for RMS within the network of the European paediatric Soft Tissue Sarcoma Study Group (EpSSG)
4. To compare the results of CWS-2007-HR with respect to EFS, OS, short- and long-term toxicities and quality of life (in a cooperation with the Late Effects Board of the GPOH) with the results of previous CWS trials and other trials within the European EpSSG-network:

Only with a randomization of the participating patients it is possible to prove or to disprove, if the additional oral therapy has an effect.

• written informed consent for registration, randomisation, data collection/transfer, and tumour material asservation available
• pathologically (including molecular pathology) proven diagnosis of rhabdomyosarcoma (RMS) or RMS-like soft tissue sarcoma (STS) and tumour material available for pathology review
• age > 6 months and < 21 years at the time of randomisation
• High-risk Group or Very High Risk Group RMS or eligible RMS-like STS: “High Risk” Group, i.e.:

• - RME, N0, M0, IRS II&III, >5 cm or > 10 in EXT, HN-PM, OTH or UG-BP
• - RME, N1, M0, any IRS-group, any size or age
• - RMA, N0, M0, any IRS-group, any size or age (exception: paratesticular RMA – not eligible
• or

• “Very High Risk” Group, i.e.:

• localised high-risk RMS-like Soft Tissue Sarcoma, i.e.:

• - SySa, any N, M0, any size or age (exception: IRS I&II, not T2b, N0, M0 – not eligible)

• no pre-existing illness preventing treatment
• no previous malignant tumours
• available for long term follow up through the treating centre
• in remission according to the CWS-2007-HR definition at the time of randomisation* after standard multimodal treatment, e.g. according to CWS-2006 guidance

• pregnant or lactating women
• other medical condition precluding treatment with protocol chemotherapy (e.g. HIV, psychiatric disorder, etc.)
• for sexuall active persons in Arm O-TIE: refusal to use contraception