Trial Information

SIOP CNS GCT II: Prospective Trial for the Diagnosis and Treatment of Children, Adolescents and Young Adults With Intracranial Germ Cell Tumors

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.