Phase III Trial of Anaplastic Glioma Without 1p/19q Loss of Heterozygosity (LOH)
Condition: Brain and Central Nervous System Tumors
MeSH terms: Nervous System Neoplasms; Central Nervous System Neoplasms
Intervention: temozolomide; DNA methylation analysis; laboratory biomarker analysis; adjuvant therapy; quality-of-life assessment; radiation therapy
Intervention description: Patients randomized to concomitant temozolomide will receive temozolomide continuously at a daily dose of 75 mg/m² during radiotherapy.; O6-Methylguanine-DNA Methyltransferase (MGMT) methylation status is used for stratification at randomization.; Prognostic factor analyses; Patients randomized to adjuvant temozolomide will start adjuvant temozolomide after a 4 week resting period after the end of radiotherapy.; Quality of Life analysis will also be used to assess neurological deterioration free progression; Radiotherapy will consist of a conventionally fractionated regimen for 6.5 weeks in a once daily schedule
Intervention MeSH terms: Temozolomide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 751.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: adult anaplastic oligodendroglioma; adult anaplastic astrocytoma

Summary:

      RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in
      chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells,
      either by killing the cells or by stopping them from dividing. Giving radiation therapy
      together with temozolomide may kill more tumor cells. It is not yet known whether giving
      temozolomide during and/or after radiation therapy is more effective than radiation therapy
      alone in treating anaplastic glioma.

      PURPOSE: This randomized phase III trial is studying giving temozolomide during and/or after
      radiation therapy to see how well it works compared to radiation therapy alone in treating
      patients with anaplastic glioma.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed diagnosis of 1 of the following:

               -  Anaplastic oligodendroglioma

               -  Anaplastic oligoastrocytoma

               -  Anaplastic astrocytoma

          -  Newly diagnosed disease

          -  Prior surgery for a low grade tumor is allowed, provided histological confirmation of
             an anaplastic tumor is present at the time of progression

          -  Absence of combined 1p/19q loss

          -  Tumor material available for central 1p/19q assessment, central O6-methylguanine-DNA
             methyltransferase promoter methylation status assessment, isocitrate dehydrogenase
             mutation analysis, and central pathology review

          -  Patients must be on a stable or decreasing dose of steroids for at least two weeks
             prior to randomization

        PATIENT CHARACTERISTICS:

          -  WHO performance status 0-2

          -  Absolute Neutrophil Count (ANC) ≥ 1.5 x 10^9 cells/L

          -  Platelet count ≥ 100 x 10^9 cells/L

          -  Bilirubin < 1.5 x upper limit of normal (ULN)

          -  Alkaline phosphatase < 2.5 x ULN

          -  Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) < 2.5 x ULN

          -  Serum creatinine < 1.5 x ULN

          -  Not pregnant or nursing

          -  Fertile patients must use effective contraception

          -  No known HIV infection or chronic hepatitis B or hepatitis C infection

          -  No other serious medical condition that would interfere with follow-up

          -  No medical condition that could interfere with oral medication intake (e.g., frequent
             vomiting or partial bowel obstruction)

          -  No other prior malignancies except for any malignancy which was treated with curative
             intent more than 5 years prior to registration and adequately controlled limited basal
             cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ
             of the cervix

          -  No prior or concurrent malignancies at other sites except for surgically cured
             carcinoma in situ of the cervix or nonmelanoma skin cancer

          -  No psychological, familial, sociological, or geographical condition that would
             potentially hamper compliance with the study protocol and follow-up schedule

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  No prior chemotherapy, including carmustine-containing wafers (Gliadel®)

          -  No prior radiotherapy to the brain

          -  No concurrent growth factors unless vital for the patient

          -  No other concurrent investigational treatment

          -  No other concurrent anticancer agents