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

Brain and Central Nervous System Tumors Clinical Trial

Official title:

SIOP Intracranial Germ Cell Tumours Protocol

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00293358
• Other study ID #: CDR0000455625
• Secondary ID: CCLG-GC-1997-01E
• Status: Completed
• Phase: Phase 3
• First received: February 16, 2006
• Last updated: September 16, 2013
• Start date: January 1997
• Est. completion date: December 2006

Study information

• Verified date: July 2008
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 500
• Est. completion date: December 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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

• ß-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

Study Design

Allocation: Non-Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Nervous System Neoplasms

Intervention

Drug:
• carboplatin

• cisplatin

• etoposide phosphate

• ifosfamide

Procedure:
• adjuvant therapy

• conventional surgery

• neoadjuvant therapy

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Ireland	Our Lady's Hospital for Sick Children	Dublin
United Kingdom	Royal Aberdeen Children's Hospital	Aberdeen	Scotland
United Kingdom	Royal Belfast Hospital for Sick Children	Belfast	Northern Ireland
United Kingdom	Birmingham Children's Hospital	Birmingham	England
United Kingdom	Institute of Child Health at University of Bristol	Bristol	England
United Kingdom	Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust	Cambridge	England
United Kingdom	Childrens Hospital for Wales	Cardiff	Wales
United Kingdom	Royal Hospital for Sick Children	Edinburgh	Scotland
United Kingdom	Royal Hospital for Sick Children	Glasgow	Scotland
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Leicester Royal Infirmary	Leicester	England
United Kingdom	Royal Liverpool Children's Hospital, Alder Hey	Liverpool	England
United Kingdom	Great Ormond Street Hospital for Children NHS Trust	London	England
United Kingdom	Royal London Hospital	London	England
United Kingdom	Central Manchester and Manchester Children's University Hospitals NHS Trust	Manchester	England
United Kingdom	Sir James Spence Institute of Child Health	Newcastle-Upon-Tyne	England
United Kingdom	Queen's Medical Centre	Nottingham	England
United Kingdom	Oxford Radcliffe Hospital	Oxford	England
United Kingdom	Children's Hospital - Sheffield	Sheffield	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	Royal Marsden NHS Foundation Trust - Surrey	Sutton	England

Sponsors (1)

Lead Sponsor	Collaborator
Children's Cancer and Leukaemia Group

Countries where clinical trial is conducted

Ireland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival			No
Primary	Event-free survival			No