Clinical Trial Finder

Inclusion Criteria:

1. 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 for all patients. 2. History and physical examination, including neurological examination, within 14 days prior to randomization. 3. Age ≥ 65 & KPS of 60

• - 70.

4. Stable or decreasing dose of corticosteroids for at least 14 days prior to randomization. 5. Laboratory evaluation within 7 days prior to randomization, with adequate function as defined below: 1. ANC ≥ 1.5 x 109/L. 2. Platelets ≥ 100 x 109/L. 3. Estimated Glomerular Filtration Rate (eGFR) > 59. 4. Total serum bilirubin ≤ 30 umol/L (ie ≤ 1.5 times ULN) 5. ALT < 150 U/L (ie < 3 times ULN) 6. AST < 120 U/L (ie < 3 times ULN) 7. Alkaline phosphatase < 390 U/L (ie < 3 times ULN) 6. Patients must sign a study-specific informed consent prior to study registration. 7. 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. 1. This will apply for male patients only and their female partner if of child bearing potential. 2. 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). 8. Male patients should agree to not donate sperm during the study treatment and for six months post treatment completion.

Exclusion Criteria:

1. Recurrent malignant gliomas. 2. Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3 years. 3. Prior head or neck RT (except for T1 glottic cancer), or systemic therapy precluding delivery of concurrent and adjuvant temozolomide. 4. Treatment with any other therapeutic clinical protocol within 30 days prior to study registration or during participation in the study. 5. Severe, active co-morbidity, defined as follows: 1. Unstable angina and/or congestive heart failure requiring hospitalization. 2. Transmural myocardial infarction within the last 6 months. 3. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of study registration. 4. Any severe, active co-morbidity precluding delivery of temozolomide. 5. History of hypersensitivity reaction to temozolomide components or to dacarbazine. 6. Active HBV infection

Arms

Active Comparator: Standard Arm: TMZ with concurrent RT (combined modality arm)

Patients will receive a total of 21 days of Temozolomide (TMZ), with 15 days of TMZ administered daily with concurrent RT. TMZ will be delivered at a dose of 75 mg/m2, given daily with RT for 15 days, one hour before each session of RT. After a 4-week break, patients will receive six cycles of adjuvant TMZ according to the standard 5-day schedule (days 1-5) every 28 days, up to 6 cycles as tolerated by the patient. The dose will be 150 mg/m2 for the first cycle and increased to 200 mg/m2 beginning with the second cycle, so long as there are no hematologic adverse events, intractable nausea or fatigue.

Experimental: Biomarker based treatment

MGMT (+) Temozolomide monotherapy: Patients will receive Temozolomide (TMZ) at a dose of 75 mg/m2 daily for 21 consecutive days. This will be followed by six cycles of TMZ according to the standard 5-day schedule (days 1-5) every 28 days. The dose will be 150 mg/m2 for the first cycle and increased to 200 mg/m2 beginning with the second cycle, so long as there are no hematologic adverse events. Dose will be determined using body surface area (BSA) calculation. MGMT methylation (-) RT monotherapy: Participants will receive radiation treatment with 40Gy / 15 fractions over a period of 21 days (3 weeks).

Interventions

Other: - Biomarker based treatment (Temozolomide monotherapy or Radiotherapy monotherapy)

Temozolomide or Radiotherapy

Combination Product: - Chemo-Radiotherapy consisting of 40 Gy in 15 daily fractions with concurrent temozolomide.

Temozolomide will be administered at a dose of 75 mg/m2 daily for a total of 21 days. This will be followed by adjuvant temozolomide (150-200 mg/m2 daily for 5 day