Patient case: 4-year-old female with neuroblastoma; genetic feature: ALK

Clinical trial: Temozolomide Followed by Radiation Therapy in Treating Children With Newly Diagnosed Malignant CNS Tumors

Summary: 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.

Detailed description: 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.

Eligibility: 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

Relevance to patient case: not relevant