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SIOP Intracranial Germ Cell Tumours Protocol

Phase 3
Open (Enrolling)
Brain and Central Nervous System Tumors

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Trial Information

SIOP Intracranial Germ Cell Tumours Protocol



- Evaluate and compare, in a non-randomized protocol, reduced-dose craniospinal
radiotherapy alone or combination chemotherapy comprising carboplatin, etoposide
phosphate, and ifosfamide and local irradiation in patients with intracranial

- Increase survival with combination chemotherapy comprising cisplatin, etoposide
phosphate, and ifosfamide followed by focal radiotherapy or craniospinal irradiation in
patients with intracranial secreting germ cell tumors.


- Use the same diagnostic protocol for imaging and laboratory investigations before,
during, and after treatment.

- Establish and use a common documentation system regarding general patient's data,
including diagnostic tests, clinical evaluation, surgery, histology, radiotherapy,
chemotherapy, and toxicity.

- Collect information about toxicity, prognostic factors, and tumor markers.

- Collect epidemiological data, including documentation of incidence and the site and the
histologic pattern of intracranial secreting and nonsecreting germ cell tumors in
children and adolescents.

- Register associated malformations in the patients as well as the epidemiology of tumors
and malformations in relatives.

OUTLINE: This is a non-randomized, multicenter study. Patients are stratified according to
tumor classification (pure CNS germinoma vs secreting germ cell tumor and embryonal

Patients in stratum I undergo biopsy or surgical resection and then begin radiotherapy with
or without chemotherapy.

- Stratum I (pure CNS germinoma [without elevated markers]): Patients receive 1 of 2
treatment options based on national/center standard:

- Option 1: Patients receive reduced-dose craniospinal radiotherapy 5 days a week
for 3 weeks followed by a boost to the tumor bed 5 days a week for 2 weeks.
Patients with multifocal or metastatic disease receive additional boosts to the
tumor sites.

- Option 2: Patients receive carboplatin IV over 1 hour on day 1, etoposide
phosphate IV over 1 hour on days 1-3 and 22-24, and ifosfamide IV over 3 hours on
days 22-26. Treatment repeats every 6 weeks for 2 courses. After recovery from
chemotherapy, patients undergo radiotherapy 5 days a week for 5 weeks.

- Stratum II (secreting tumors and embryonal carcinoma): Patients receive etoposide
phosphate IV over 1 hour on days 1-3, cisplatin IV over 1 hour on days 1-5, and
ifosfamide IV over 22 hours on days 1-5. Treatment repeats every 3 weeks for up to 4
courses. Patients whose tumor markers do not return to normal after completion of
chemotherapy are off protocol. Patients may undergo surgery after chemotherapy course 2
or 4 if required. After completion of chemotherapy and recovery from surgery, patients
with nonmetastatic disease undergo radiotherapy to the tumor bed 5 day a week for 6
weeks, and patients with metastatic disease undergo radiotherapy to the cerebrum,
spinal axis, and tumor bed for 7 weeks.

After completion of study treatment, patients are followed for 4 weeks and then

PROJECTED ACCRUAL: Approximately 500 patients will be accrued for this study.

Inclusion Criteria


- Clinical and radiological evidence of intracranial germ cell tumor, classified as 1
of the following:

- Germinoma

- Pure germinoma

- Germinoma with mature and/or immature teratoma

- Secreting germ cell tumor

- Elevated tumor markers in serum and/or cerebral spinal fluid as evidenced
by any of the following:

- Alpha-fetoprotein > 25 ng/mL

- β-human choriogonadotropin > 50 IU/L

- Any tumor containing 1 of these components:

- Yolk sac tumor

- Choriocarcinoma

- Embryonal tumor

- Normal tumor markers allowed

- Diagnosis confirmed by histology or elevated serum markers

- Metastatic or nonmetastatic disease

- Two separate tumors in the suprasellar and pineal areas without evidence of
metastatic disease elsewhere are considered nonmetastatic multifocal disease

- Study treatment must begin ≤ 4 weeks after diagnosis

- No pure immature or mature teratomas

- The following additional patients are eligible:

- Patients who are > 18 years of age provided no other appropriate protocol exists

- Patients who were diagnosed > 4 weeks ago

- Patients who are in relapse


- Not specified


- No prior treatment except surgery

- No concurrent amino glycosides or other nephrotoxic drugs during ifosfamide

- No concurrent growth factors

- No other concurrent chemotherapy or radiotherapy

Type of Study:


Study Design:

Allocation: Non-Randomized, Primary Purpose: Treatment

Outcome Measure:


Safety Issue:


Principal Investigator

James Nicholson, DM, MA, MRCPCH

Investigator Role:

Study Chair

Investigator Affiliation:

Cambridge University Hospitals NHS Foundation Trust


United States: Federal Government

Study ID:




Start Date:

January 1997

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • childhood central nervous system germ cell tumor
  • adult central nervous system germ cell tumor
  • childhood central nervous system choriocarcinoma
  • childhood central nervous system embryonal tumor
  • childhood central nervous system yolk sac tumor
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms
  • Neoplasms, Germ Cell and Embryonal