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

Phase II Treatment of Children With Newly Diagnosed Malignant Central Nervous System Tumors With Temozolomide Prior to Radiation Therapy

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.

Study Overview

• Status: Completed
• Conditions: Brain and Central Nervous System Tumors; Neuroblastoma
• Intervention / Treatment: Drug: temozolomide

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Henry S. Friedman, MD, Duke University

Study record dates

Study Major Dates

• Study Start: August 1, 2000
• Study Completion (Actual): September 1, 2002

Study Registration Dates

• First Submitted: July 5, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): June 20, 2013
• Last Update Submitted That Met QC Criteria: June 19, 2013
• Last Verified: October 1, 2009

More Information

Terms related to this study

• Keywords: childhood high-grade cerebral astrocytoma; disseminated neuroblastoma; stage 4S neuroblastoma; regional neuroblastoma; untreated childhood medulloblastoma; untreated childhood cerebellar astrocytoma; childhood infratentorial ependymoma; newly diagnosed childhood ependymoma; childhood supratentorial ependymoma; childhood oligodendroglioma; childhood craniopharyngioma; childhood choroid plexus tumor; childhood grade I meningioma; childhood grade II meningioma; childhood grade III meningioma; localized resectable neuroblastoma; childhood low-grade cerebral astrocytoma; untreated childhood supratentorial primitive neuroectodermal tumor; untreated childhood visual pathway and hypothalamic glioma; childhood central nervous system choriocarcinoma; childhood central nervous system embryonal tumor; childhood central nervous system mixed germ cell tumor; childhood central nervous system teratoma; childhood central nervous system yolk sac tumor
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Nervous System Neoplasms; Central Nervous System Neoplasms; Neuroblastoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: 0931; DUMC-0931-02-6R3; DUMC-000931-00-5R1; DUMC-0831-99-5; NCI-G00-1799; DUMC-000931-01-6R1; CDR0000067936 (Other Identifier: NCI)