Combination Chemotherapy and Radiation Therapy With or Without Methotrexate in Treating Young Patients With Newly Diagnosed Gliomas

NCT00278278 | Unknown Phase 3

• 3 other identifiers: CDR0000454723GPOH-HIT-GBM-DEU-205100
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether giving methotrexate together with combination chemotherapy and radiation therapy is more effective than combination chemotherapy and radiation therapy alone in treating gliomas. PURPOSE: This randomized phase III trial is studying giving methotrexate together with combination chemotherapy and radiation therapy to see how well it works compared to combination chemotherapy and radiation therapy alone in treating young patients with newly diagnosed gliomas.

Conditions

Brain and Central Nervous System Tumors

Keywords

untreated childhood brain stem glioma; untreated childhood cerebellar astrocytoma; childhood high-grade cerebral astrocytoma; childhood spinal cord neoplasm

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS) rate at 5.5 years

Secondary Outcomes (6)

• Comparison of OS, progression-free survival, and event-free survival with historical control annually

• Long-term sequelae annually

• Tumor response

• Progression-free survival

• Event-free survival

Study Arms (2)

Arm I

EXPERIMENTAL

Patients receive high-dose methotrexate IV over 24 hours on days 1 and 15 and leucovorin calcium IV every 6 hours on days 2-3 an 16-17. Four weeks later, patients undergo external beam radiotherapy once daily, 5 days a week, for approximately 6 weeks. Beginning on the first day of radiotherapy, patients receive cisplatin IV over 1 hour on days 1-5, etoposide IV over 2 hours on days 1-3, and vincristine IV on days 5, 12, 19, 26, and 33. Beginning seven days prior to completion of radiotherapy, patients receive ifosfamide IV over 1 hour and cisplatin IV over 1 hour on days 1-5, etoposide IV over 2 hours on days 1-3, and vincristine IV on day 5.

Drug: cisplatin; Drug: etoposide; Drug: ifosfamide; Drug: lomustine; Drug: methotrexate; Drug: prednisone; Drug: vincristine sulfate

Arm II

ACTIVE COMPARATOR

Patients undergo external beam radiotherapy once daily, 5 days a week, for approximately 6 weeks. Beginning on the first day of radiotherapy, patients receive cisplatin IV over 1 hour on days 1-5, etoposide IV over 2 hours on days 1-3, and vincristine IV on days 5, 12, 19, 26, and 33. Beginning seven days prior to completion of radiotherapy, patients receive ifosfamide IV over 1 hour and cisplatin IV over 1 hour on days 1-5, etoposide IV over 2 hours on days 1-3, and vincristine IV on day 5.

Drug: cisplatin; Drug: etoposide; Drug: ifosfamide; Drug: lomustine; Drug: prednisone; Drug: vincristine sulfate

Interventions

cisplatin DRUG

Given IV

Arm I; Arm II

etoposide DRUG

Given IV

Arm I; Arm II

ifosfamide DRUG

Given IV

Arm I; Arm II

lomustine DRUG

Given IV

Arm I; Arm II

methotrexate DRUG

Given IV

Arm I

prednisone DRUG

Given IV

Arm I; Arm II

vincristine sulfate DRUG

Given IV

Arm I; Arm II

Eligibility Criteria

• Age: 3 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * Newly diagnosed tumors of the brain or spinal cord, meeting one of the following criteria: * Histologically\* confirmed diagnosis of 1 of the following high-grade gliomas: * Glioblastoma (WHOº IV) * Anaplastic astrocytoma (WHOº III) * Gliosarcoma (WHOº III or IV) * Anaplastic oligo-astrocytoma NOTE: \*Histological requirement may be waived for other types of brainstem glioma * Radiologically proven diffuse intrinsic pontine glioma * Second malignancy or disseminate metastases or multifocal tumors are allowed if the field of irradiation is not too large * No diffuse metastases making craniospinal irradiation necessary PATIENT CHARACTERISTICS: * No cardiorespiratory insufficiency requiring medical respiration * No low blood pressure requiring systemic catecholamines * No severe neurological damage (e.g., coma) * No tetraplegia without possibility to communicate * No other poor clinical condition * Not pregnant * Fertile patients must use effective contraception * No hypersensitivity to methotrexate, cisplatin, vincristine, lomustine, or ifosfamide * No other malignancy preceding radiotherapy that does not allow further radiation PRIOR CONCURRENT THERAPY: * No prior chemotherapy for brain tumor * The following prior therapies are allowed: * Mistletoe * H15 (extract of Boswellia serrata) * Homeopathy therapy with dilution \> 4D * Alternative medicine without proven efficacy * No prior radiotherapy for brain tumor * No concurrent alcohol or tobacco consumption * No concurrent participation in another study

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• German Society for Pediatric Oncology and Hematology GPOH gGmbH: lead

Study Sites (1)

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4009, United States

Location

Related Publications (1)

• Wolff JE, Kortmann RD, Wolff B, Pietsch T, Peters O, Schmid HJ, Rutkowski S, Warmuth-Metz M, Kramm C. High dose methotrexate for pediatric high grade glioma: results of the HIT-GBM-D pilot study. J Neurooncol. 2011 May;102(3):433-42. doi: 10.1007/s11060-010-0334-2. Epub 2010 Aug 8.

  PMID: 20694800 RESULT

MeSH Terms

Conditions

Central Nervous System Neoplasms; Astrocytoma; Spinal Cord Neoplasms

Interventions

Cisplatin; Etoposide; Ifosfamide; Lomustine; Methotrexate; Prednisone; Vincristine

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Spinal Cord Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Study Officials

• Christoph Kramm, MD

  University Children's Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 16, 2006
• First Posted: January 18, 2006
• Study Start: September 1, 2003
• Primary Completion: March 1, 2010
• Last Updated: December 19, 2013

Record last verified: 2008-11

Locations

US (1)