Combination Chemotherapy and Radiation Therapy in Treating Patients With Germ Cell Tumors in the Brain
SIOP Intracranial Germ Cell Tumours Protocol
  • Phase

    Phase 3
  • Study Type

  • Status

    Completed No Results Posted
  • Intervention/Treatment

    ifosfamide carboplatin cisplatin etoposide ...
  • Study Participants

RATIONALE: Drugs used in chemotherapy, such as carboplatin, etoposide, ifosfamide, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving more than one drug (combination chemotherapy) with radiation therapy may kill more tumor cells.

PURPOSE: This phase III trial is studying combination chemotherapy followed by radiation therapy to see how well it works compared to radiation therapy alone in treating patients with germ cell tumors in the brain.


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 germinoma.
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 carcinoma).

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 periodically.

PROJECTED ACCRUAL: Approximately 500 patients will be accrued for this study.
Study Started
Jan 31
Study Completion
Dec 31
Last Update
Sep 17

Drug carboplatin

Drug cisplatin

Drug etoposide phosphate

Drug ifosfamide

Procedure adjuvant therapy

Procedure conventional surgery

Procedure neoadjuvant therapy

Radiation radiation therapy



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


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

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 administration
No concurrent growth factors
No other concurrent chemotherapy or radiotherapy
No Results Posted