Chemoradiotherapy Versus Biomarker-Guided Therapy for Elderly and Frail GBM Patients
Glioblastoma Multiforme
About this trial
This is an interventional treatment trial for Glioblastoma Multiforme
Eligibility Criteria
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 for all patients.
- 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
- 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:
- 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
Sites / Locations
- Tom Baker Cancer CentreRecruiting
- Cross Cancer InstituteRecruiting
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
Standard Arm: TMZ with concurrent RT (combined modality arm)
Biomarker based treatment
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.
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).