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

NCT01424839 | Unknown Phase 4 DMC

• 2 other identifiers: UKM08_00572009-018072-33
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Intracranial Germ Cell Tumors

Keywords

SIOP CNS GCT II; Patients with the primary disease of an Intracranial Germ Cell Tumors

Outcome Measures

Primary Outcomes (1)

• survival

  Survival rates in respect to applied treatment , according to Kaplan-Meier estimation , 5 years event free survival

  5 years event free survival

Secondary Outcomes (2)

• short and long term toxicity

  until 7 years after start of trial

• overall survival

  7 years after start of trial

Study Arms (7)

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)

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)

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

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)

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

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)

Radiation: craniospinal irradiation; Drug: Cisplatin, Etoposide, Ifosfamide (high dose)

Teratoma

NO INTERVENTION

collection of information on surgery, applied treatment and outcome

Interventions

craniospinal irradiation RADIATION

* 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 metastatic; Non-Germinoma metastatic high risk; Non-Germinoma metastatic standard risk

Carboplatin, Etoposide, Ifosfamide DRUG

• 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

germinoma non-metastatic

ventricular irradiation RADIATION

* 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)

germinoma non-metastatic

Cisplatin, etoposide, Ifosfamide (standard) DRUG

Four courses of Etoposide, Cisplatin and Ifosfamide (standard treatment )

Non-Germinoma metastatic standard risk; Non-germinoma non-metastatic standard risk

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

Non-Germinoma metastatic high risk; Non-germinoma non-metastatic high risk

focal irradiation RADIATION

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

Non-germinoma non-metastatic high risk; Non-germinoma non-metastatic standard risk

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital Muenster: lead
• Deutsche Kinderkrebsstiftung: collaborator
• Hannover Medical School: collaborator
• German Society for Pediatric Oncology and Hematology GPOH gGmbH: collaborator

Study Sites (1)

University Hospital Muenster

Münster, 48129, Germany

RECRUITING

Related Publications (1)

• 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.

  PMID: 33633029 DERIVED

MeSH Terms

Interventions

Craniospinal Irradiation; Ice; Cisplatin; Etoposide; Ifosfamide

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Water; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds; Environment; Ecological and Environmental Phenomena; Biological Phenomena; Weather; Meteorological Concepts; Environment and Public Health; Chlorine Compounds; Nitrogen Compounds; Platinum Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Gabriele Calaminus, MD

  University Hospital Muenster

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gabriele Calaminus, MD

CONTACT

+492518358060; gabriele.calaminus@ukmuenster.de

Carmen Teske

CONTACT

+492518358055; carmen.teske@ukmuenster.de

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2011
• First Posted: August 29, 2011
• Study Start: October 1, 2011
• Primary Completion: October 1, 2018
• Study Completion: October 1, 2018
• Last Updated: June 4, 2015

Record last verified: 2015-06

Locations

DE (1)