RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Chemotherapy combined with radiation therapy may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of temozolomide followed by radiation therapy in treating children who have newly diagnosed malignant central nervous system tumors.

Condition	Treatment or Intervention	Phase
childhood brain tumor childhood nerve tumor	Drug: temozolomide  Procedure: chemotherapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the response rate to treatment with temozolomide in children with newly diagnosed malignant central nervous system tumors.
• Determine the toxicity of this treatment in these patients.
• Determine the overall survival in these patients for 18 months following the study after receiving this treatment.

OUTLINE: Patients are stratified according to type of disease (ependymoma vs brain stem glioma vs malignant glioma vs other).

Patients receive oral temozolomide on days 1-5. Treatment repeats every 28 days for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. Patients with a partial or complete response may receive an additional 8 courses of temozolomide following radiotherapy.

PROJECTED ACCRUAL: A maximum of 100 patients (25 per stratum) will be accrued for this study over 24-36 months.

Ages Eligible for Study:  4 Years   -   21 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed newly diagnosed malignant central nervous system tumor not requiring immediate radiotherapy
• Patients with diffuse pontine tumors do not require histological confirmation
• Eligible types include the following:
• Ependymoma
• Malignant glioma
• Anaplastic astrocytoma
• Glioblastoma multiforme
• Anaplastic oligodendroglioma
• Gliosarcoma
• Anaplastic mixed oligoastrocytoma
• Brainstem glioma
• Primitive neuroectodermal tumor
• Nongerminoma germ cell tumor
• At least one bidimensionally measurable lesion
• At least 1.5 cm2 within 72 hours of surgical resection or greater than 14 days after surgery
• Diffuse pontine tumors are not required to be measurable
• Neurologically stable

PATIENT CHARACTERISTICS: Age:

• 4 to 21

Performance status:

• Karnofsky or Lansky 70-100%

Life expectancy:

• Greater than 12 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10 g/dL

Hepatic:

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase less than 2 times ULN
• SGOT and SGPT less than 2.5 times ULN

Renal:

• BUN and creatinine less than 1.5 times ULN

Other:

• Must be able to swallow capsules
• No acute infection treated with intravenous antibiotics
• No nonmalignant systemic disease that makes patient a poor medical risk
• No frequent vomiting or medical condition that may interfere with oral medication intake (e.g., partial bowel obstruction)
• No other prior or concurrent malignancies except surgically cured carcinoma in situ of the cervix or basal or squamous cell carcinoma of the skin
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No more than one prior biologic therapy regimen
• No concurrent biologic therapy
• No concurrent growth factors or epoetin alfa

Chemotherapy:

• No more than one prior chemotherapy regimen
• No other concurrent chemotherapy

Endocrine therapy:

• No increasing doses of steroids within one week of study

Radiotherapy:

• See Disease Characteristics
• No concurrent radiotherapy

Surgery:

• At least 2 weeks, but no greater than 4 weeks, since prior surgical resection and recovered

Other:

• No other concurrent investigational drugs

North Carolina
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States

Study chairs or principal investigators

Henry S. Friedman, MD,  Study Chair,  Duke Comprehensive Cancer Center   

Study ID Numbers:  CDR0000067936; DUMC-0931-02-6R3; DUMC-000931-00-5R1; DUMC-0831-99-5; NCI-G00-1799; DUMC-000931-01-6R1
Record last reviewed:  February 2003
Last Updated:  October 13, 2004
Record first received:  July 5, 2000
ClinicalTrials.gov Identifier:  NCT00005955
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08