Prospective Trial for the Diagnosis and Treatment of Intracranial Germ Cell Tumors (SIOPCNSGCTII)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by University Hospital Muenster
Sponsor:
Collaborators:
Deutsche Kinderkrebsstiftung
Hannover Medical School
Gesellschaft fur Padiatrische Onkologie und Hamatologie - Germany
Information provided by (Responsible Party):
University Hospital Muenster
ClinicalTrials.gov Identifier:
NCT01424839
First received: August 11, 2011
Last updated: January 22, 2013
Last verified: January 2013
  Purpose

STUDY DESIGN:

Prospective, non-randomised multicentre study with patients stratified according to risk groups INVESTIGATIONAL MEDICINAL PRODUCTS The IMPs on this trial are Carboplatin, Cisplatin, Ifosfamide and Etoposide (as approved by German competent authority).

PRIMARY 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 irradiation (+/- 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

SECONDARY OBJECTIVES:

Germinoma

  • To minimise long term effects of irradiation by sparing spinal and whole brain radiotherapy in non-metastatic disease Malignant non-germinoma
  • In standard risk to maintain EFS with chemotherapy and local irradiation Teratoma
  • To evaluate the influence of surgery and treatment on outcome to assist in the development of a fu-ture treatment strategy For all histological subtypes
  • To improve accuracy of diagnosis and staging in all registered patients
  • To standardise neurosurgical intervention
  • For all patients requiring biopsy or resection according to protocol guidelines, to collect and to store tumour material, and CSF where possible, for use in future biological studies.

ENDPOINTS / Criteria for evaluation:

Main end point

Event-free survival, defined as minimum time from the date of diagnosis to:

  • Death from any cause
  • Relapse
  • Progressive disease on therapy
  • Or second malignancy

Secondary end points

  • Overall survival, defined as time to death from any cause, measured from the date of diagnosis
  • Short and long term toxicity.

Condition Intervention Phase
Intracranial Germ Cell Tumors
Radiation: craniospinal irradiation
Drug: Carboplatin, Etoposide, Ifosfamide
Radiation: ventricular irradiation
Drug: Cisplatin, etoposide, Ifosfamide (standard)
Drug: Cisplatin, Etoposide, Ifosfamide (high dose)
Radiation: focal irradiation
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: SIOP CNS GCT II: Prospective Trial for the Diagnosis and Treatment of Children, Adolescents and Young Adults With Intracranial Germ Cell Tumors

Resource links provided by NLM:


Further study details as provided by University Hospital Muenster:

Primary Outcome Measures:
  • survival [ Time Frame: 5 years event free survival ] [ Designated as safety issue: Yes ]
    Survival rates in respect to applied treatment , according to Kaplan-Meier estimation , 5 years event free survival


Secondary Outcome Measures:
  • short and long term toxicity [ Time Frame: until 7 years after start of trial ] [ Designated as safety issue: Yes ]
    toxicity of treatment will be assessed with CTC criteria, severe toxicity will be analysed by safety desk

  • overall survival [ Time Frame: 7 years after start of trial ] [ Designated as safety issue: Yes ]
    Overall survival will be measured by Kaplan -Meier Estimation , 5 years overall survival


Estimated Enrollment: 400
Study Start Date: October 2011
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Germinoma metastatic

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

Radiotherapy

  • 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)
  • 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)
Radiation: craniospinal irradiation
  • 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 intracra-nial metastases and spinal deposits (total tumour dose 40 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)
  • Patients with metastastic non-germinomatous 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)
germinoma non-metastatic

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

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
  • 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)
Drug: Carboplatin, Etoposide, Ifosfamide
• 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
Radiation: ventricular irradiation
  • 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
  • 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)
Non-germinoma non-metastatic standard risk

Chemotherapy:

• Standard risk non-germinomatous malignant GCT Four courses of Etoposide, Cisplatin and Ifosfamide (standard treatment ) After Chemotherapy: 54 Gy focal radiotherapy in 30 fractions

Drug: Cisplatin, etoposide, Ifosfamide (standard)
Four courses of Etoposide, Cisplatin and Ifosfamide (standard treatment )
Radiation: focal irradiation
• Patients with localised non-germinomatous disease at diagnosis After Chemotherapy: 54 Gy focal radiotherapy in 30 fractions
Non-Germinoma metastatic standard risk
Chemotherapy Four courses of Etoposide, Cisplatin and Ifosfamide (standard treatment ) Radiotherapy After Chemotherapy: 30 Gy (20 fractions) to craniospinal 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)
Radiation: craniospinal irradiation
  • 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 intracra-nial metastases and spinal deposits (total tumour dose 40 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)
  • Patients with metastastic non-germinomatous 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)
Drug: Cisplatin, etoposide, Ifosfamide (standard)
Four courses of Etoposide, Cisplatin and Ifosfamide (standard treatment )
Non-germinoma non-metastatic high risk
Chemotherapy Two courses of standard Etoposide, Cisplatin and Ifosfamide, followed by two dose intensified courses of Etoposide, Cisplatin and Ifosfamide with stem cell support Radiotherapy After Chemotherapy: 54 Gy focal radiotherapy in 30 fractions
Drug: Cisplatin, Etoposide, Ifosfamide (high dose)
Two courses of standard Etoposide, Cisplatin and Ifosfamide, followed by two dose intensified courses of Etoposide, Cisplatin and Ifosfamide with stem cell support
Radiation: focal irradiation
• Patients with localised non-germinomatous disease at diagnosis After Chemotherapy: 54 Gy focal radiotherapy in 30 fractions
Non-Germinoma metastatic high risk
Chemotherapy Two courses of standard Etoposide, Cisplatin and Ifosfamide, followed by two dose intensified courses of Etoposide, Cisplatin and Ifosfamide with stem cell support Radiotherapy After Chemotherapy: 30 Gy (20 fractions) to craniospinal 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)
Radiation: craniospinal irradiation
  • 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 intracra-nial metastases and spinal deposits (total tumour dose 40 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)
  • Patients with metastastic non-germinomatous 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)
Drug: Cisplatin, Etoposide, Ifosfamide (high dose)
Two courses of standard Etoposide, Cisplatin and Ifosfamide, followed by two dose intensified courses of Etoposide, Cisplatin and Ifosfamide with stem cell support
No Intervention: Teratoma
collection of information on surgery, applied treatment and outcome

  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01424839

Contacts
Contact: Gabriele Calaminus, MD +492518358060 gabriele.calaminus@ukmuenster.de
Contact: Carmen Teske +492518358055 carmen.teske@ukmuenster.de

Locations
Germany
University Hospital Muenster Recruiting
Muenster, Germany, 48129
Contact: Gabriele Calaminus, MD    +492518358060    gabriele.calaminus@ukmuenster.de   
Contact: Carmen Teske    +492518358055    carmen.teske@ukmuenster.de   
Principal Investigator: Gabriele Calaminus, MD         
Sponsors and Collaborators
University Hospital Muenster
Deutsche Kinderkrebsstiftung
Hannover Medical School
Gesellschaft fur Padiatrische Onkologie und Hamatologie - Germany
Investigators
Principal Investigator: Gabriele Calaminus, MD University Hospital Muenster
  More Information

Additional Information:
No publications provided

Responsible Party: University Hospital Muenster
ClinicalTrials.gov Identifier: NCT01424839     History of Changes
Other Study ID Numbers: UKM08_0057, 2009-018072-33
Study First Received: August 11, 2011
Last Updated: January 22, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University Hospital Muenster:
SIOP CNS GCT II
Patients with the primary disease of an Intracranial Germ Cell Tumors

Additional relevant MeSH terms:
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Etoposide phosphate
Isophosphamide mustard
Cisplatin
Etoposide
Ifosfamide
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on August 26, 2014