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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00293358
First received: February 16, 2006
Last updated: September 16, 2013
Last verified: July 2008
  Purpose

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: carboplatin
Drug: cisplatin
Drug: etoposide phosphate
Drug: ifosfamide
Procedure: adjuvant therapy
Procedure: conventional surgery
Procedure: neoadjuvant therapy
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Primary Purpose: Treatment
Official Title: SIOP Intracranial Germ Cell Tumours Protocol

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Survival [ Designated as safety issue: No ]
  • Event-free survival [ Designated as safety issue: No ]

Estimated Enrollment: 500
Study Start Date: January 1997
Study Completion Date: December 2006
Detailed Description:

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00293358

Locations
Ireland
Our Lady's Hospital for Sick Children
Dublin, Ireland, 12
United Kingdom
Birmingham Children's Hospital
Birmingham, England, United Kingdom, B4 6NH
Institute of Child Health at University of Bristol
Bristol, England, United Kingdom, BS2 8AE
Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust
Cambridge, England, United Kingdom, CB2 2QQ
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, United Kingdom, LS9 7TF
Leicester Royal Infirmary
Leicester, England, United Kingdom, LE1 5WW
Royal Liverpool Children's Hospital, Alder Hey
Liverpool, England, United Kingdom, L12 2AP
Great Ormond Street Hospital for Children NHS Trust
London, England, United Kingdom, WC1N 3JH
Royal London Hospital
London, England, United Kingdom, E1 1BB
Central Manchester and Manchester Children's University Hospitals NHS Trust
Manchester, England, United Kingdom, M27 4HA
Sir James Spence Institute of Child Health
Newcastle-Upon-Tyne, England, United Kingdom, NE1 4LP
Queen's Medical Centre
Nottingham, England, United Kingdom, NG7 2UH
Oxford Radcliffe Hospital
Oxford, England, United Kingdom, 0X3 9DU
Children's Hospital - Sheffield
Sheffield, England, United Kingdom, S10 2TH
Southampton General Hospital
Southampton, England, United Kingdom, SO16 6YD
Royal Marsden NHS Foundation Trust - Surrey
Sutton, England, United Kingdom, SM2 5PT
Royal Belfast Hospital for Sick Children
Belfast, Northern Ireland, United Kingdom, BT12 6BE
Royal Aberdeen Children's Hospital
Aberdeen, Scotland, United Kingdom, AB25 2ZG
Royal Hospital for Sick Children
Edinburgh, Scotland, United Kingdom, EH9 1LF
Royal Hospital for Sick Children
Glasgow, Scotland, United Kingdom, G3 8SJ
Childrens Hospital for Wales
Cardiff, Wales, United Kingdom, CF14 4XW
Sponsors and Collaborators
Children's Cancer and Leukaemia Group
Investigators
Study Chair: James Nicholson, DM, MA, MRCPCH Cambridge University Hospitals NHS Foundation Trust
Investigator: Marie C. Baranzelli, MD Centre Oscar Lambret
Investigator: U. Gobel, MD Heinrich-Heine University, Duesseldorf
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00293358     History of Changes
Other Study ID Numbers: CDR0000455625, CCLG-GC-1997-01, EU-20579, SIOP-CNS-GCT-96
Study First Received: February 16, 2006
Last Updated: September 16, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
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

Additional relevant MeSH terms:
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Germ Cell and Embryonal
Neoplasms by Site
Neoplasms
Nervous System Diseases
Neoplasms by Histologic Type
Etoposide phosphate
Isophosphamide mustard
Cisplatin
Etoposide
Ifosfamide
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on August 20, 2014