Radiation Therapy With or Without Temozolomide in Treating Patients With Anaplastic Glioma

Location:

Rochester, MN., Jacksonville, FL.

Trial status:

Open for Enrollment

Why is this study being done?

OBJECTIVES:

     Primary

       -  To assess whether concurrent radiotherapy with daily temozolomide improves overall survival as compared to no daily temozolomide in patients with non-1p/19q deleted anaplastic glioma.

       -  To assess whether adjuvant temozolomide improves survival as compared to no adjuvant temozolomide in patients with non-1p/19q deleted anaplastic glioma.

     Secondary

       -  To assess whether concurrent and adjuvant temozolomide prolongs progression-free survival and neurological deterioration-free survival in patients with non-1p/19q deleted anaplastic glioma.

       -  To assess the safety of concurrent and adjuvant temozolomide in patients with non-1p/19q deleted anaplastic glioma, including late effects on cognition.

       -  To assess the impact of concurrent and adjuvant temozolomide on the quality of life of patients with non-1p/19q deleted anaplastic glioma.

     OUTLINE: This is a multicenter study. Patients are stratified according to institution, WHO performance status (0 vs > 0), age (≤ 50 vs > 50), presence of 1p LOH only (yes vs no), presence of oligodendroglial elements (yes vs no), and O6-methylguanine-DNA methyltransferase promoter methylation status (methylated vs unmethylated vs indeterminate). Patients are randomized to 1 of 4 treatment arms.

       -  Arm I: Patients undergo radiotherapy* once daily, 5 days a week, for 6.5 weeks (total of 33 fractions).

       -  Arm II: Patients undergo radiotherapy* once daily, 5 days a week and receive oral temozolomide once daily for 6.5 weeks (total of 33 fractions of radiotherapy).

       -  Arm III: Patients undergo radiotherapy* once daily, 5 days a week for 6.5 weeks (total of 33 fractions). Beginning 4 weeks after completion of radiotherapy, patients receive adjuvant oral temozolomide once daily on days 1-5. Treatment with adjuvant temozolomide repeats every 28 days for up to 12 courses.

       -  Arm IV: Patients undergo radiotherapy* once daily, 5 days a week and receive oral temozolomide once daily for 6.5 weeks (total of 33 fractions of radiotherapy). Beginning 4 weeks after completion of radiotherapy, patients receive adjuvant oral temozolomide once daily on days 1-5. Treatment with adjuvant temozolomide repeats every 28 days for up to 12 courses.

     NOTE: *Patients must begin radiotherapy within 8 days after randomization and within 7 weeks after surgery.

     In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.

     Patients complete quality-of-life questionnaires, including QLQ-C30 version 3, BCM20, and the Mini Mental Status Exam at baseline, 4 weeks after the completion of radiotherapy, and then every 3 months for 5 years.

     Tissue samples are collected at baseline for histology review, 1p/19q analysis, methylation status of the O6-methylguanine-DNA methyltransferase promoter, and isocitrate dehydrogenase mutation analysis.

     After completion of study treatment, patients are followed every 3 months.

Who is eligible to participate?

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

         -  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

         -  AST and 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

Last updated:

9/16/2011

NCT ID:

NCT00626990

IRB Number:

10-005232