SIOP CNS GCT II

Author: J. Dobke, erstellt am: 2011/11/07, Last modification: 2019/09/17

Title SIOP CNS GCT II: Prospective Trial for the diagnosis and treatment of children, adolescents and young adults with Intracranial Germ Cell Tumours
Disease Intracranial Germ Cell Tumours
Type Prospective, non-randomised multicentre study with patients stratified according to risk groups
Problem / Objectives

Germinoma

  • To maintain current high event-free survival (EFS) rates using a risk adapted approach
  • In localised germinoma: to omit whole brain and spinal irradiation by using combined treatment with standard chemotherapy and ventricular irradiation (+/- boosts)
  • In bifocal tumours (pineal + suprasellar): to treat as non-metastatic disease and to omit whole brain and spinal irradiation by using combined treatment with standard chemotherapy and ventricular irra-diation (+/- boosts)
  • In metastatic disease: to maintain current excellent EFS in metastatic germinoma with craniospinal irradiation

Malignant non-germinoma

To improve EFS:

  • by dose escalation of chemotherapy in patients identified as high risk at diagnosis ( age < 6 years and/or AFP serum / CSF > 1000 ng/ml)
  • by standardising the surgical approach for residual disease after treatment

Teratoma

  • To register patients and collect data regarding diagnostics, treatment and outcome in order to develop future treatment strategies
Therapy / Study arms

Germinoma

Chemotherapy:

Non-metastatic fully staged germinoma (± teratoma)
Two courses (1 and 3) of Etoposide and Carboplatin, alternating with two courses (2 and 4) of Etoposide and Ifosfamide
Note: Bifocal germinoma (pineal+suprasellar) are treated as non-metastatic germinoma, if staging shows no additional dissemination

Metastatic or incompletely staged germinomas (± teratoma)
Do not receive chemotherapy in this protocol

Radiotherapy:

Non-metastatic pure germinoma in PR/SD
After Chemotherapy: 24 Gy (15 fractions) to whole ventricles with a 16 Gy (10 fraction) boost to tumour bed (total tumour dose 40 Gy)

Non-metastatic germinoma in CR
After Chemotherapy: 24 Gy (15 fractions) to whole ventricles

Metastatic or incompletely staged pure germinoma
24 Gy (15 fractions) to craniospinal axis with a 16 Gy (10 fraction) boost to tumour bed and any intracranial metastases and spinal deposits (total tumour dose 40 Gy)

Non-metastatic germinoma plus teratoma (incompletely resected)
After Chemotherapy: 24 Gy (15 fractions) to whole ventricles; 30.4 Gy (19 fraction) boost to tumour bed (total tumour dose 54.4 Gy)

Metastatic germinoma plus teratoma (incompletely resected)
24 Gy (15 fractions) to craniospinal axis ; 30.4 Gy (19 fraction) boost to tumour bed and 16 Gy (10 frac-tion) boost to metastases (total tumour dose 54.4 Gy)

NON-GERMINOMA (± TERATOMA)

Chemotherapy:

Standard risk non-germinomatous malignant GCT
Four courses of Etoposide, Cisplatin and Ifosfamide (standard treatment )

High risk non-germinomatous malignant GCT
Two courses of standard Etoposide, Cisplatin and Ifosfamide, followed by two dose intensified courses of Etoposide, Cisplatin and Ifosfamide with stem cell support
Resection of residual tumour after 3 courses chemotherapy (if indicated), followed by: 4th course. If vi-able cells are found in the resected tumour specimen patient is transferred to the high risk arm

Radiotherapy for standard and high risk non-germinomatous malignant GCT:

Patients with localised disease at diagnosis
After Chemotherapy: 54 Gy focal radiotherapy in 30 fractions

Patients with metastastic disease at diagnosis

After Chemotherapy: 30 Gy (20 fractions) to cranio-spinal axis with 24 Gy (15 fraction) boosts to tumour site and any intracranial metastases (total tumour dose 54 Gy) and 20.8 Gy (13 fraction) boosts to spinal deposits (total dose 50.8 Gy)

Inclusion Criteria
  • Main residence in one of the participating countries
  • Primary diagnosis of an intracranial germ cell tumour
  • Written consent for trial participation, treatment according to the protocol and consent for data transfer
Exclusion Criteria
  • Tumour entity other than primary intracranial germ cell tumour or CNS GCT as second malignancy
  • Primary diagnosis pre-dating the opening of SIOP CNS GCT II in the participating country of registration
  • Medical, psychiatric or social conditions incompatible with trial treatment or treatment according to protocol is not intended
  • Participation within a different trial for treatment of germ cell tumours and/or concurrent treatment within any other clinical trial. The only exceptions to this are trials with different endpoints, involving aspects of supportive treatment which can run parallel to SIOP CNS GCT II without influencing the outcome of this trial e.g. trials on antiemetics, antimycotics, antibiotics, strategies for psychosocial support etc.
  • Pregnancy and lactation
  • Any treatment not given according to protocol prior to registration
Recruitment 400 malignant germ cell tumours
Status October 2011 to 01/07/2018 (end of recruitment); end of trial: 01/07/2010
EudraCT 2009-018072-33
Entry Study Register ClinicalTrials.gov: NCTNCT01424839
Principal Investigator Dr. Gabriele Calaminus
E-Mail mailto:makei@uni-muenster.de
Contact

Chief Investigator

Dr. med. Gabriele Calaminus
Universitätsklinikum Bonn Zentrum für Kinderheilkunde
Päd. Hämatologie/ Onkologie
Konrad-Adenauer-Allee 119
53113 Bonn
Telefon +49 (228) 287 33305
Fax +49 (228) 287 33605
Gabriele.Calaminus@ukb.uni-bonn.de

Data management

Carmen Teske

Reference pathologists

Dr. med. Christian Vokuhl
Institut für Pathologie der Universität Kiel
Sektion Kinderpathologie, Haus 14
Arnold-Heller-Str. 3
24105 Kiel
Telefon +49 (431) 500 15603
Fax +49 (431) 500 15604
cvokuhl@path.uni-kiel.de

Prof. Dr. med. Torsten Pietsch
Institut für Neuropathologie
ME der Universität
Sigmund-Freud-Str. 25
53105 Bonn
Telefon +49 (228) 287 16602
Fax +49 (228) 287 14331
t.pietsch@uni-bonn.de

Referenence radiology

Prof. Dr. Monika Warmuth-Metz
Universitätsklinikum Würzburg
Abt. für Neuroradiologie
Josef-Schneider-Str. 11
97080 Würzburg
Telefon +49 (931) 201 34799
Fax +49 (931) 201 34789
hit@ukw.de

Participants GPOH, France, Italy, Denmark, Sweden, Norway, Finland, Spain, Netherlands, Great Britain
Sponsoring Deutsche Kinderkrebsstiftung