Medpedia

Combination Chemotherapy and Radiation Therapy in Treating Patients With Germ Cell Tumors in the Brain

Active, not recruiting
01/01/1997 to Present
500
Phase 3
Interventional

Conditions

  • Brain and Central Nervous System Tumors

Eligibility

any age
No
DISEASE CHARACTERISTICS:
- 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
PATIENT CHARACTERISTICS:
- Not specified
PRIOR CONCURRENT THERAPY:
- 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

Purpose

OBJECTIVES:

Primary

- 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.

Secondary

- 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.

Interventions

  • Drug: carboplatin
  • Drug: cisplatin
  • Drug: etoposide phosphate
  • Drug: ifosfamide
  • Procedure: adjuvant therapy
  • Procedure: conventional surgery
  • Procedure: neoadjuvant therapy
  • Radiation: radiation therapy

Outcome Measures

  • Survival
    Safety Issue: No
  • Event-free survival
    Safety Issue: No

Officials

  • James Nicholson, DM, MA, MRCPCH
    Study Chair, Cambridge University Hospitals NHS Foundation Trust
  • Marie C. Baranzelli, MD
    Centre Oscar Lambret
  • U. Gobel, MD
    Heinrich-Heine University, Duesseldorf

Locations

  • Childrens Hospital for Wales
    Cardiff, Wales, CF14 4XW, United Kingdom
    Active, not recruiting
  • Royal Hospital for Sick Children
    Glasgow, Scotland, G3 8SJ, United Kingdom
    Active, not recruiting
  • Royal Hospital for Sick Children
    Edinburgh, Scotland, EH9 1LF, United Kingdom
    Active, not recruiting
  • Royal Aberdeen Children's Hospital
    Aberdeen, Scotland, AB25 2ZG, United Kingdom
    Active, not recruiting
  • Royal Belfast Hospital for Sick Children
    Belfast, Northern Ireland, BT12 6BE, United Kingdom
    Active, not recruiting
  • Royal Marsden NHS Foundation Trust - Surrey
    Sutton, England, SM2 5PT, United Kingdom
    Active, not recruiting
  • Southampton General Hospital
    Southampton, England, SO16 6YD, United Kingdom
    Active, not recruiting
  • Children's Hospital - Sheffield
    Sheffield, England, S10 2TH, United Kingdom
    Active, not recruiting
  • Oxford Radcliffe Hospital
    Oxford, England, 0X3 9DU, United Kingdom
    Active, not recruiting
  • Queen's Medical Centre
    Nottingham, England, NG7 2UH, United Kingdom
    Active, not recruiting
  • Sir James Spence Institute of Child Health
    Newcastle-Upon-Tyne, England, NE1 4LP, United Kingdom
    Active, not recruiting
  • Central Manchester and Manchester Children's University Hospitals NHS Trust
    Manchester, England, M27 4HA, United Kingdom
    Active, not recruiting

Sponsors

  • Children's Cancer and Leukaemia Group
    Lead Sponsor
  • United States: Federal Government

Links

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