Clinical trial NCT00876031: Trial for Localised High-risk Rhabdomyosarcoma and Rhabdomyosarcoma-like Soft Tissue Sarcoma
Official title: A Randomised Phase-III Trial of the Cooperative Weichteilsarkom Study Group (CWS) for Localised High-risk Rhabdomyosarcoma and Localised Rhabdomyosarcoma-like Soft Tissue Sarcoma in Children, Adolescents, and Young Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Soft Tissue Sarcoma
Keywords: pediatric soft tissue sarcoma
rhabdomyosarcoma
extraosseous Ewing family tumours
synovial sarcoma
undifferentiated sarcoma
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
Collaborators: name: Cooperative Weichteilsarkom Study Group
name: Deutsche Kinderkrebsstiftung
name: German Society for Pediatric Oncology and Hematology GPOH gGmbH
name: Gesellschaft fur Padiatrische Onkologie und Hamatologie - Austria
name: The Swedish Childhood Solid Tumor Working Group
name: Polish Paediatric Solid Tumours Study Group
name: Swiss Pediatric Oncology Group
First posted: 2009-04-06
Enrollment: 195
Sex: ALL
Minimum age (years): 6
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is 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.


Eligibility criteria: 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
* Rhabdomyosarcoma of the "High Risk" Group, i.e.:

  * RME, N0, M0, IRS II\&III, \>5 cm or \>10 years in EXT, HN-PM, OTH, UG-BP
  * RME, N1, M0, any IRS-group, any size or age
  * RMA, NO, M0, any IRS-group, any size or age (exception: paratesticular RMA are not eligible) or
* Rhabdomyosarcoma of the "Very High Risk" Group, i.e.:

  * RMA, N1, MO, IRS II\&III, any size or age or
  * localised high-risk RMS-like Soft Tissue Sarcoma, i.e.:
  * EES, pPNET, UDS: any N, M0, any IRS-group, any size or age
  * SySa, any N, M0, any size or age (exception: SySa IRSI\&II, not T2b, N0, M0 are not eligible)
* no pre-existing illness preventing treatment (esp. those listed in the medicinal product information, e.g. cardiac, hepatic, metabolic, or renal dysfunction; hypersensitivity)
* no previous malignant tumours
* available for long term follow up through the treating centre
* in remission (according to the CWS-2007-HR definition (see X7.1.8X)) at the time of randomisation after standard multimodal therapy e.g. according to the CWS-guidance

Exclusion Criteria:

* pregnant or lactating women
* other medical condition precluding treatment with protocol therapy (e.g. HIV, psychiatric disorder, etc.)
* for sexually active females and males in Arm B (O-TIE treatment): refusal to use effective contraception (e.g. oral, IUD)

Primary outcomes:
measure: event free survival (EFS)
timeFrame: 3 years
Secondary outcomes:
measure: Overall survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Dornbirn
country: Austria
facility: Krankenhaus der Stadt Dornbirn
city: Graz
country: Austria
facility: Universitätsklinik für Kinder- und Jugendheilkunde
city: Innsbruck
country: Austria
facility: Universitätsklinik für Kinder- und Jugendheilkunde
city: Klagenfurt
country: Austria
facility: Landeskrankenhaus
city: Leoben
country: Austria
facility: Landeskrankenhaus
city: Linz
country: Austria
facility: Landesfrauen - und Kinderklinik Linz
city: Salzburg
country: Austria
facility: St. Johanns Spital / Landeskrankenhaus
city: Wien
country: Austria
facility: St. Anna Kinderspital
city: Aachen
country: Germany
facility: Universitätsklinikum
city: Augsburg
country: Germany
facility: Klinikum Augsburg
city: Berlin
country: Germany
facility: Charité
city: Berlin
country: Germany
facility: Helios Klinikum Berlin-Buch
city: Bielefeld
country: Germany
facility: Krankenhaus Bielefeld
city: Bonn
country: Germany
facility: Universitätskinderklinik
city: Braunschweig
country: Germany
facility: Klinikum Braunschweig
city: Bremen
country: Germany
facility: Prof. Hess Kinderklinik
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz
city: Datteln
country: Germany
facility: Vestische Kinderklinik
city: Dortmund
country: Germany
facility: Westfälisches Kinderzentrum, Klinikum Dortmund
city: Dresden
country: Germany
facility: Universitätsklinikum
city: Düsseldorf
country: Germany
facility: Universitätskinderklinik
city: Erfurt
country: Germany
facility: Helios Klinikum
city: Erlangen
country: Germany
facility: Universitätsklinikum
city: Essen
country: Germany
facility: Universitätsklinikum
city: Frankfurt
country: Germany
facility: Universitätsklinikum
city: Freiburg
country: Germany
facility: Universitätsklinikum
city: Giessen
country: Germany
facility: Universitätsklinikum
city: Greifswald
country: Germany
facility: Universitätsklinikum
city: Göttingen
country: Germany
facility: Universitätsklinikum
city: Halle
country: Germany
facility: Universitätsklinikum
city: Hamburg
country: Germany
facility: Universitätsklinikum
city: Hannover
country: Germany
facility: Medizinische Hochschule
city: Heidelberg
country: Germany
facility: Universitätsklinikum
city: Herdecke
country: Germany
facility: Gemeinschaftskrankenhaus Herdecke
city: Homburg
country: Germany
facility: Universitätsklinikum
city: Jena
country: Germany
facility: Universitätsklinikum
city: Karlsruhe
country: Germany
facility: Städtisches Klinikum Karlsruhe
city: Kassel
country: Germany
facility: Klinikum Kassel
city: Kiel
country: Germany
facility: Universitätsklinikum
city: Koblenz
country: Germany
facility: Gemeinschaftsklinikum Mayen-Koblenz
city: Köln
country: Germany
facility: Kliniken der Stadt Köln
city: Köln
country: Germany
facility: Universitätsklinikum
city: Leipzig
country: Germany
facility: Universitätsklinikum
city: Lübeck
country: Germany
facility: Universitätsklinikum
city: Magdeburg
country: Germany
facility: Universitätsklinikum
city: Mainz
country: Germany
facility: Universitätsklinikum
city: Mannheim
country: Germany
facility: Universitätsklinikum
city: Minden
country: Germany
facility: Klinikum Minden
city: München
country: Germany
facility: Dr. von Haunersches Kinderspital
city: München
country: Germany
facility: Krankenhaus München Schwabing
city: Münster
country: Germany
facility: Universitätsklinikum
city: Nürnberg
country: Germany
facility: Cnopf'sche Kinderklinik
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg
city: Regensburg
country: Germany
facility: Universitätsklinikum
city: Rostock
country: Germany
facility: Universitätsklinikum
city: Sankt Augustin
country: Germany
facility: Asklepios Kinderklinik
city: Schwerin
country: Germany
facility: Helios Kliniken Schwerin
city: Stuttgart
country: Germany
facility: Olgahospital
city: Trier
country: Germany
facility: Mutterhaus der Borromäerinnen
city: Tübingen
country: Germany
facility: Universitätsklinikum
city: Ulm
country: Germany
facility: Universitätsklinikum
city: Würzburg
country: Germany
facility: Universitätsklinikum
city: Białystok
country: Poland
facility: Medical University
city: Bydgoszcz
country: Poland
facility: Collegium Medicum
city: Gdansk
country: Poland
facility: Medical Academy
city: Katowice
country: Poland
facility: Silesian Medical Academy
city: Kraków
country: Poland
facility: Polish-American Institute of Paediatrics Jagiellonian University Medical College
city: Lublin
country: Poland
facility: Medical Academy
city: Szczecin
country: Poland
facility: Pian Medical University
city: Warszawa
country: Poland
facility: Department of Surgical Oncology for Children and Youth
city: Wroclaw
country: Poland
facility: Medical University
city: Łódź
country: Poland
facility: Medical Academy
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital, The Queen Siliva Childrens Hospital
city: Linköping
country: Sweden
facility: University Hospital, Dept. of Pediatrics
city: Lund
country: Sweden
facility: University Hospital, Dept. of Pediatric Hematology and Oncology
city: Stockholm
country: Sweden
facility: Karolinska University Hospital, Astrid Lindgrens Children's Hospital
city: Umea
country: Sweden
facility: Norrland's University Hospital, Dept. of Pediatrics
city: Uppsala
country: Sweden
facility: Children's University Hospital
city: Aarau
country: Switzerland
facility: Kantonsspital
city: Basel
country: Switzerland
facility: Universitätskinderklinik beider Basel
city: Bellinzona
country: Switzerland
facility: Ospedale San Giovanni
city: Bern
country: Switzerland
facility: Inselspital University hospital
city: Geneve
country: Switzerland
facility: Hopital Cantonal de Geneve
city: Lausanne
country: Switzerland
facility: CHUV
city: Luzern
country: Switzerland
facility: Kinderspital
city: Sankt Gallen
country: Switzerland
facility: Ostschweizer Kinderspital
city: Zurich
country: Switzerland
facility: University Children's Hospital
Study officials:
affiliation: Olgahospital, CWS
name: Ewa Koscielniak, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitätsklinikum Frankfurt, CWS
name: Thomas Klingebiel, MD
role: STUDY_CHAIR
affiliation: Olgahospital, CWS
name: Monika Sparber Sauer, MD
role: STUDY_DIRECTOR
References:
citation: Dantonello TM, Int-Veen C, Harms D, Leuschner I, Schmidt BF, Herbst M, Juergens H, Scheel-Walter HG, Bielack SS, Klingebiel T, Dickerhoff R, Kirsch S, Brecht I, Schmelzle R, Greulich M, Gadner H, Greiner J, Marky I, Treuner J, Koscielniak E. Cooperative trial CWS-91 for localized soft tissue sarcoma in children, adolescents, and young adults. J Clin Oncol. 2009 Mar 20;27(9):1446-55. doi: 10.1200/JCO.2007.15.0466. Epub 2009 Feb 17.
citation: Mattke AC, Bailey EJ, Schuck A, Dantonello T, Leuschner I, Klingebiel T, Treuner J, Koscielniak E. Does the time-point of relapse influence outcome in pediatric rhabdomyosarcomas? Pediatr Blood Cancer. 2009 Jul;52(7):772-6. doi: 10.1002/pbc.21906.
citation: Dantonello TM, Int-Veen C, Winkler P, Leuschner I, Schuck A, Schmidt BF, Lochbuehler H, Kirsch S, Hallmen E, Veit-Friedrich I, Bielack SS, Niggli F, Kazanowska B, Ladenstein R, Wiebe T, Klingebiel T, Treuner J, Koscielniak E. Initial patient characteristics can predict pattern and risk of relapse in localized rhabdomyosarcoma. J Clin Oncol. 2008 Jan 20;26(3):406-13. doi: 10.1200/JCO.2007.12.2382.
citation: Weihkopf T, Blettner M, Dantonello T, Jung I, Klingebiel T, Koscielniak E, Luckel M, Spix C, Kaatsch P. Incidence and time trends of soft tissue sarcomas in German children 1985-2004 - a report from the population-based German Childhood Cancer Registry. Eur J Cancer. 2008 Feb;44(3):432-40. doi: 10.1016/j.ejca.2007.11.013.
citation: Koscielniak E, Morgan M, Treuner J. Soft tissue sarcoma in children: prognosis and management. Paediatr Drugs. 2002;4(1):21-8. doi: 10.2165/00128072-200204010-00003.
citation: Dantonello TM, Winkler P, Boelling T, Friedel G, Schmid I, Mattke AC, Ljungman G, Bielack SS, Klingebiel T, Koscielniak E; CWS Study Group. Embryonal rhabdomyosarcoma with metastases confined to the lungs: report from the CWS Study Group. Pediatr Blood Cancer. 2011 May;56(5):725-32. doi: 10.1002/pbc.22862. Epub 2010 Nov 8.
citation: Siepermann M, Koscielniak E, Dantonello T, Klee D, Boos J, Krefeld B, Borkhardt A, Hoehn T, Asea A, Wessalowski R. Oral low-dose chemotherapy: successful treatment of an alveolar rhabdomyosarcoma during pregnancy. Pediatr Blood Cancer. 2012 Jan;58(1):104-6. doi: 10.1002/pbc.22934. Epub 2011 Jan 16.
citation: Klingebiel T, Boos J, Beske F, Hallmen E, Int-Veen C, Dantonello T, Treuner J, Gadner H, Marky I, Kazanowska B, Koscielniak E. Treatment of children with metastatic soft tissue sarcoma with oral maintenance compared to high dose chemotherapy: report of the HD CWS-96 trial. Pediatr Blood Cancer. 2008 Apr;50(4):739-45. doi: 10.1002/pbc.21494.