Intracranial Germ Cell TumorsPhase 4SIOPCNSGCTIINCT01424839
Prospective Trial for the Diagnosis and Treatment of Intracranial Germ Cell Tumors
A Phase 4 study testing craniospinal irradiation, Carboplatin, Etoposide, Ifosfamide and ventricular irradiation in people with Intracranial Germ Cell Tumors, run by University Hospital Muenster at 1 site in Germany.
Trial summary
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). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Intracranial Germ Cell Tumors
- What is being tested?
- craniospinal irradiation, Carboplatin, Etoposide, Ifosfamide and ventricular irradiation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 400 participants
- Where
- 1 siteGermany
- Study dates
- Oct 2011to Oct 2018
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
University Hospital Muenster
Münster, 48129
Gabriele Calaminus, MD, +492518358060, gabriele.calaminus@ukmuenster.de
Carmen Teske, +492518358055, carmen.teske@ukmuenster.de
About this study
Official title: SIOP CNS GCT II: Prospective Trial for the Diagnosis and Treatment of Children, Adolescents and Young Adults With Intracranial Germ Cell Tumors
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).
Read more
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.
Read the detailed description
PATIENT POPULATION Age of patients: no lower or upper age limit; Estimated number: 400 malignant germ cell tumours
Diagnosis and main criteria for inclusion/exclusion:
Intracranial Germ Cell tumours of any histology and intracranial site and dissemination
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 trans-fer
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
TREATMENT:
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 stag-ing 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 metastatic disease at diagnosis 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)
SPECIAL ASPECTS:
Central response evaluation on a national basis:
Germinoma: In all patients with localised germinoma a central national radiological review is mandatory for response evaluation to chemotherapy and decision if only ventricular irradiation or an additional tu-mour boost has to be performed.
Non-Germinoma: After three courses of chemotherapy to evaluate response to treatment and to deter-mine necessity of surgery in case of residual before radiotherapy.
- Conditions
- Intracranial Germ Cell Tumors
- Being tested
- craniospinal irradiation, Carboplatin, Etoposide, Ifosfamide, ventricular irradiation, Cisplatin, etoposide, Ifosfamide (standard), Cisplatin, Etoposide, Ifosfamide (high dose)
- Keywords
- SIOP CNS GCT II, Patients with the primary disease of an Intracranial Germ Cell Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
craniospinal irradiationRadiation
- 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)
Carboplatin, Etoposide, IfosfamideDrug
- 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
ventricular irradiationRadiation
- 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)
Cisplatin, etoposide, Ifosfamide (standard)Drug
Four courses of Etoposide, Cisplatin and Ifosfamide (standard treatment )
Cisplatin, Etoposide, Ifosfamide (high dose)Drug
Two courses of standard Etoposide, Cisplatin and Ifosfamide, followed by two dose intensified courses of Etoposide, Cisplatin and Ifosfamide with stem cell support
focal irradiationRadiation
- Patients with localised non-germinomatous disease at diagnosis After Chemotherapy: 54 Gy focal radiotherapy in 30 fractions
| Study group | Role | What they receive |
|---|---|---|
| Germinoma metastatic | Other | • 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) Receives: Radiation: craniospinal irradiation |
| germinoma non-metastatic | Other | 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) Receives: Drug: Carboplatin, Etoposide, Ifosfamide; Radiation: ventricular irradiation |
| Non-germinoma non-metastatic standard risk | Other | 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 Receives: Drug: Cisplatin, etoposide, Ifosfamide (standard); Radiation: focal irradiation |
| Non-Germinoma metastatic standard risk | Other | 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) Receives: Radiation: craniospinal irradiation; Drug: Cisplatin, etoposide, Ifosfamide (standard) |
| Non-germinoma non-metastatic high risk | Other | 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 Receives: Drug: Cisplatin, Etoposide, Ifosfamide (high dose); Radiation: focal irradiation |
| Non-Germinoma metastatic high risk | Other | 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) Receives: Radiation: craniospinal irradiation; Drug: Cisplatin, Etoposide, Ifosfamide (high dose) |
| Teratoma | No intervention | collection of information on surgery, applied treatment and outcome |
What is being measured
The primary outcome is the main question the study is designed to answer.
survival
Survival rates in respect to applied treatment , according to Kaplan-Meier estimation , 5 years event free survival
Measured: 5 years event free survival
Secondary outcomes (2)
short and long term toxicity
toxicity of treatment will be assessed with CTC criteria, severe toxicity will be analysed by safety desk
Measured: until 7 years after start of trial
overall survival
Overall survival will be measured by Kaplan -Meier Estimation , 5 years overall survival
Measured: 7 years after start of trial
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2011 (estimated)
- Study startOct 2011
- Primary completionOct 2018 (estimated)
- Study completionOct 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Intracranial Germ Cell TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Muenster
- Sponsor type
- University, hospital or other
- Collaborators
- Deutsche Kinderkrebsstiftung, Hannover Medical School, German Society for Pediatric Oncology and Hematology GPOH gGmbH
- Responsible party
- Sponsor
- Investigators
- Gabriele Calaminus, MD, Principal investigator, University Hospital Muenster
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01424839
- Sponsor's protocol ID
- UKM08_0057
- Other IDs
- 2009-018072-33, 2009
- Acronym
- SIOPCNSGCTII
- Status last verified
- Jun 2015
- First submitted
- 11 Aug 2011
- Last updated
- 4 Jun 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Rajagopal R, Leong SH, Jawin V, Foo JC, Ahmad Bahuri NF, Mun KS, Azman RR, Loh J, Yap TY, Ariffin H, Moreira DC, Gottardo NG, Bouffet E, Ganesan D. Challenges in the Management of Childhood Intracranial Germ Cell Tumors in Middle-Income Countries: A 20-Year Retrospective Review From a Single Tertiary Center in Malaysia. J Pediatr Hematol Oncol. 2021 Oct 1;43(7):e913-e923. doi: 10.1097/MPH.0000000000002116.
PubMed 33633029
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SIOP CNS GCT II: Prospective Trial for the Diagnosis and Treatment of Children, Adolescents and Young Adults With Intracranial Germ Cell Tumors
- ClinicalTrials.gov ID
- NCT01424839
- Acronym / sponsor ID
- SIOPCNSGCTII / UKM08_0057
- Conditions
- Intracranial Germ Cell Tumors
- Keywords
- SIOP CNS GCT II, Patients with the primary disease of an Intracranial Germ Cell Tumors
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- University Hospital MuensterUniversity, hospital or other
- Collaborators
- Deutsche Kinderkrebsstiftung, Hannover Medical School, German Society for Pediatric Oncology and Hematology GPOH gGmbH
- Study start
- Oct 2011
- Primary completion
- Oct 2018 (estimated)
- Study completion
- Oct 2018 (estimated)
- First posted
- 29 Aug 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PATIENT POPULATION Age of patients: no lower or upper age limit; Estimated number: 400 malignant germ cell tumours
Diagnosis and main criteria for inclusion/exclusion:
Intracranial Germ Cell tumours of any histology and intracranial site and dissemination
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 trans-fer
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
TREATMENT:
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 stag-ing 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 metastatic disease at diagnosis 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)
SPECIAL ASPECTS:
Central response evaluation on a national basis:
Germinoma: In all patients with localised germinoma a central national radiological review is mandatory for response evaluation to chemotherapy and decision if only ventricular irradiation or an additional tu-mour boost has to be performed.
Non-Germinoma: After three courses of chemotherapy to evaluate response to treatment and to deter-mine necessity of surgery in case of residual before radiotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Germinoma metastatic | Other | Radiation: craniospinal irradiation• 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) |
| germinoma non-metastatic | Other | Drug: Carboplatin, Etoposide, Ifosfamide, Radiation: ventricular irradiationChemotherapy: • 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) |
| Non-germinoma non-metastatic standard risk | Other | Drug: Cisplatin, etoposide, Ifosfamide (standard), Radiation: focal irradiationChemotherapy: • Standard risk non-germinomatous malignant GCT Four courses of Etoposide, Cisplatin and Ifosfamide (standard treatment ) After Chemotherapy: 54 Gy focal radiotherapy in 30 fractions |
| Non-Germinoma metastatic standard risk | Other | Radiation: craniospinal irradiation, Drug: Cisplatin, etoposide, Ifosfamide (standard)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) |
| Non-germinoma non-metastatic high risk | Other | Drug: Cisplatin, Etoposide, Ifosfamide (high dose), Radiation: focal irradiationChemotherapy 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 |
| Non-Germinoma metastatic high risk | Other | Radiation: craniospinal irradiation, Drug: Cisplatin, Etoposide, Ifosfamide (high dose)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) |
| Teratoma | No intervention | –collection of information on surgery, applied treatment and outcome |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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) | Radiation | Germinoma metastatic, Non-Germinoma metastatic high risk, Non-Germinoma metastatic standard risk |
| 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 | Drug | germinoma non-metastatic |
| 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) | Radiation | germinoma non-metastatic |
| Cisplatin, etoposide, Ifosfamide (standard)Four courses of Etoposide, Cisplatin and Ifosfamide (standard treatment ) | Drug | Non-Germinoma metastatic standard risk, Non-germinoma non-metastatic standard risk |
| 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 | Drug | Non-Germinoma metastatic high risk, Non-germinoma non-metastatic high risk |
| focal irradiation• Patients with localised non-germinomatous disease at diagnosis After Chemotherapy: 54 Gy focal radiotherapy in 30 fractions | Radiation | Non-germinoma non-metastatic high risk, Non-germinoma non-metastatic standard risk |
Primary outcome
survival
Time frame: 5 years event free survival
Survival rates in respect to applied treatment , according to Kaplan-Meier estimation , 5 years event free survival
2 secondary outcomes
short and long term toxicity
Time frame: until 7 years after start of trial
overall survival
Time frame: 7 years after start of trial
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2015.
- Derived from this study: PubMed 33633029Rajagopal R, Leong SH, Jawin V, Foo JC, Ahmad Bahuri NF, Mun KS, Azman RR, Loh J, Yap TY, Ariffin H, Moreira DC, Gottardo NG, Bouffet E, Ganesan D. Challenges in the Management of Childhood Intracranial Germ Cell Tumors in Middle-Income Countries: A 20-Year Retrospective Review From a Single Tertiary Center in Malaysia. J Pediatr Hematol Oncol. 2021 Oct 1;43(7):e913-e923. doi: 10.1097/MPH.0000000000002116.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gabriele Calaminus, MD principal investigator
University Hospital Muenster
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing craniospinal irradiation, Carboplatin, Etoposide, Ifosfamide and ventricular irradiation in people with Intracranial Germ Cell Tumors, run by University Hospital Muenster at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Gabriele Calaminus, MD (+492518358060, gabriele.calaminus@ukmuenster.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
survival (time frame: 5 years event free survival). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01424839, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2015.