Chemoradiotherapy Versus Chemotherapy for Elderly and Frail GBM Patients

Inclusion criteria

• Newly-diagnosed, histologically proven, intracranial glioblastoma with maximal safe resection. Biopsy alone is expected if resection is not possible. MGMT promoter methylation status must be tested and the results positive (defined as all non-negative MGMT status, including intermediate or indeterminate status (i.e., with cutoff higher than the MGMT negative threshold).
• History and physical examination, including neurological examination, within 14 days prior to randomization.
• Age ≥ 65 & KPS of 60 - 70
• Stable or decreasing dose of corticosteroids for at least 14 days prior to randomization.
• Laboratory evaluation within 7 days prior to randomization, with adequate function as defined below:

• ANC ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Serum creatinine ≤ 1.5 times ULN or estimated Glomerular Filtration Rate (eGFR) > 59
• Total serum bilirubin ≤ 30 umol/L (ie ≤ 1.5 times ULN)
• ALT < 150 U/L (ie < 3 times ULN)
• AST < 120 U/L (ie < 3 times ULN)
• Alkaline phosphatase < 390 U/L (ie < 3 times ULN)
• Patients must sign a study-specific informed consent prior to study registration.
• Patients of childbearing / reproductive potential should use highly effective birth control methods, as defined by the investigator, during the study treatment period and for a period of 6 months after the last dose of study drug. A highly effective method of birth control is defined as those that result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.

Note: abstinence is acceptable if this is established and preferred contraception for the patient and is accepted as a local standard.

• This will apply for male patients only and their female partner if of child bearing potential.
• Effective contraception should also be used by male patients taking temozolomide. Men being treated with temozolomide are advised not to father a child during or up to 6 months after discontinuation of treatment (male patients).
• Male patients should agree to not donate sperm during the study treatment and for six months post treatment completion.

Exclusion criteria

• Negative MGMT promoter methylation status, or a status of not reportable.
• Recurrent malignant gliomas
• Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3 years.
• Prior head or neck RT (except for T1 glottic cancer), or systemic therapy precluding delivery of concurrent and adjuvant temozolomide
• Treatment with any other therapeutic clinical protocol within 30 days prior to study registration or during participation in the study.
• Severe, active co-morbidity, defined as follows:

• Unstable angina and/or congestive heart failure requiring hospitalization
• Transmural myocardial infarction within the last 6 months
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of study registration
• Any severe, active co-morbidity precluding delivery of temozolomide.
• History of hypersensitivity reaction to temozolomide components or to dacarbazine.
• Active HBV infection