Clinical Trial Finder

DISEASE CHARACTERISTICS:

• - Histopathologically confirmed glioblastoma multiforme.

• - Grade IV disease by WHO classification.

• - Newly diagnosed disease.

• - Initial diagnostic surgery or biopsy performed within the past 4 weeks.

• - Not a candidate for standard radiotherapy (60Gy/30 fractions over 6 weeks) in combination with temozolomide.

PATIENT CHARACTERISTICS:

• - ECOG performance status 0-2.

• - Absolute granulocyte count ≥ 1,500/mm³ - Platelet count ≥ 100,000/mm³ - Creatinine ≤ 1.5 times upper limit of normal (ULN) - Bilirubin ≤ 1.5 times ULN.

• - ALT and AST < 2.5 times ULN.

• - No known hypersensitivity to temozolomide or compounds with similar chemical composition to temozolomide.

• - No history of other malignancies except adequately treated nonmelanoma skin cancer, curatively treated in situ cancer of the cervix, or other curatively treated solid tumors with no evidence of disease for at least 5 years.

• - No serious active infection (e.g., wound infection requiring parenteral antibiotics) or other serious underlying medical conditions that would preclude study treatment.

• - No other condition (e.g., psychological or geographical) that would preclude study compliance.

PRIOR CONCURRENT THERAPY:

• - No prior chemotherapy.

• - No prior radiotherapy.

• - No prior or concurrent investigational therapy.

• - No concurrent surgical procedures for tumor debulking.

• - No concurrent stereotactic boost radiotherapy.

• - No other concurrent chemotherapy, immunotherapy, or biological therapy.

• - No concurrent epoetin alfa.

- Concurrent corticosteroids allowed provided the patient has been on a stable or decreasing dose for at least 14 days

OBJECTIVES: Primary.

• - Compare overall survival rates in older patients with newly diagnosed glioblastoma multiforme treated with short-course radiotherapy with or without temozolomide.

Secondary.

• - Compare progression-free survival of patients treated with these regimens.

• - Compare the nature, severity, and frequency of adverse events in patients treated with these regimens.

• - Compare the quality of life of patient treated with these regimens.

• - Determine the methylation status of the O6-methylguanine-DNA methyltransferase promoter.

OUTLINE: This is a multicenter, randomized study. Patients are stratified according to center, age (65-70 years vs.#46;71-75 years vs.#46;≥ 76 years), ECOG performance status (0-1 vs.#46; 2), and extent of resection at surgery (biopsy only vs.#46;complete or incomplete resection). Patients are randomized to 1 of 2 treatment arms.

• - Arm I: Patients undergo radiotherapy once daily on days 1-5, 8-12, and 15-19 in the absence of disease progression or unacceptable toxicity.

• - Arm II: Patients undergo radiotherapy as in arm I and receive oral temozolomide once daily on days 1-25.

Beginning 4 weeks after completion of radiotherapy and temozolomide, patients receive adjuvant oral temozolomide once daily on days 1-5. Treatment with temozolomide alone repeats every 28 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients complete quality of life questionnaires at baseline and periodically during study treatment. Tissue samples are collected at baseline and analyzed for methylation status of the O6-methylguanine-DNA methyltransferase promoter. After completion of study treatment, patients are followed every 3 months.

Arms

Active Comparator: Temozolomide

Temozolomide and short course radiation

Active Comparator: Radiation

Short course radiation alone

Interventions

Drug: - temozolomide

Temozolomide (concurrent with radiation) 75 mg/m2 PO 3 weeks once a day, daily, from the first day to the last day of radiotherapy, but for no longer than 28 days, and then adjuvantly for up to 12 cycles (150 mg/m2 for the first 5 days of each cycle). Adjuvant TMZ may be escalated to 200mg/m2 in C2 onward if appropriate.

Genetic: - DNA methylation analysis

A stratified log-rank test, adjusting for the stratification factors (except centre) plus MGMT promoter methylation status, will be used as the primary method to compare the overall survival between the two arms

Procedure: - quality-of-life assessment

prior to randomization until end of study

Radiation: - Radiation

Short course radiotherapy