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

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

Interventions

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

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)

DRUG

Cisplatin, etoposide, Ifosfamide (standard)

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

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

Sponsors & Collaborators

• Deutsche Kinderkrebsstiftung

  collaborator OTHER

• Hannover Medical School

  collaborator OTHER

• German Society for Pediatric Oncology and Hematology GPOH gGmbH

  collaborator OTHER

• University Hospital Muenster

  lead OTHER

Principal Investigators

• Gabriele Calaminus, MD · University Hospital Muenster

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-10-31

Primary Completion

2018-10-31

Completion

2018-10-31

Countries

• Germany

Study Locations