Author:  CWS, Last modification: 2022/03/18


A randomised phase-III trial of the Cooperative Soft-Tissue-Study-Group for localised high-risk habdomyosarcoma and localised Rhabdomyosarcoma-like Soft Tissue Sarcoma in children, adolescents, and young adults


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

Problem / Objectives

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.

Therapy / Study arms

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
• 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.

Inclusion Criteria
  • 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
Exclusion Criteria
  • 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
Recruitment 375 patients, 320 of which have been randomised
Status 01.07.2009-30.06.2015; observation ends on 30/06/2020
EudraCT 2007-001478-10
Entry Study Register
Principal Investigator Prof. Dr. med. Ewa Koscielniak, agency Prof. Dr. med. Thomas Klingebiel


Prof. Dr. med. Ewa Koscielniak Klinikum Stuttgart - Olgahospital Klinik für Kinder- und Jugendmedizin - Pädiatrie 5 Kriegsbergstr. 62 70174 Stuttgart Telefon +49 (711) 278 72461, 72463 Fax +49 (711) 278 72749

Prof. Dr. med. Thomas Klingebiel Klinikum der Johann-Wolfgang-Goethe-Universität Zentrum für Kinder- und Jugendmedizin, Klinik III Theodor-Stern-Kai 7 60590 Frankfurt Telefon +49 (69) 6301 5094 Fax +49 (69) 6301 6700

Dokumentation Deutschland

Erika Hallmen Klinikum Stuttgart - Olgahospital Klinik f. Kinder-u.Jugendmedizin, Pädiatrie 5, Studienzentrale CWS Kriegsbergstr. 62 70174 Stuttgart Telefon +49 (711) 278 73875 Fax +49 (711) 278 72749

Investigator Austria

Prof. Dr. med. Ruth Ladenstein St. Anna-Kinderspital Children´s Cancer Research Institute (CCRI) Kinderspitalgasse 6 1090 Wien Telefon +43 (1) 40470 4750 Fax +43 (1) 40470 7430

Investigator Poland

Prof. Dr. Bernarda Kazanowska Wroclaw Medical Universtity Department of Pediatric Hematology/Oncology and BMT, Supraregional Center of Pediatric Oncology "Cape of Hope" 213 Borowska St. 50-556 Wroclaw Telefon +48 (71) 7332840 Fax +48 (71) 7332709

Investigator Sweden

Prof. Dr. med. Gustaf Ljungman Children´s University Hospital Department of Pediatric Hematology and Oncology S-751-85 Uppsala Telefon +46 (18) 611-5586 Fax +46 (18) 50-0949

Investigator Swizzerland

Felix Niggli Kinderspital Zürich - Eleonorenstiftung Klinik für Onkologie Steinwiesstr. 75 CH-8032 Zürich Telefon +41 (44) 266 7823 Fax +41 (44) 266 7834

Participants Germany, Austria, Poland, Swizzerland
Weitere Informationen Sponsor: Universitätsklinikum Tübingen
Link(s) Literature on soft-tissue tumours/sarcomas
Sponsoring The CWS-2007-HR trial is supported by the Deutsche Kinderkrebsstiftung
The "Förderkreis Krebskranke Kinder Stuttgart e.V." suppprts the study coordiantion centre in Stuttgart