Comparing treatments for elderly patients with glioblastoma

A Randomized Controlled Trial of Chemo-Radiotherapy Versus Chemotherapy for Elderly and Frail Patients With Newly Diagnosed Glioblastoma

This study is testing if a personalized treatment based on a specific gene marker can help older patients with glioblastoma live as long as traditional chemotherapy and radiation, while causing fewer side effects.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 107 (estimated)
• Ages: 65 Years and up
• Sex: All
• Sponsor: AHS Cancer Control Alberta (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 2 sites (Calgary, Alberta and 1 other locations)
• Trial ID: NCT04765514 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of biomarker-guided therapy versus traditional chemoradiotherapy in elderly patients with glioblastoma multiforme who have poor performance status. The study focuses on patients aged 65 and older, assessing whether treatment based on the methylation status of the MGMT promoter can provide similar survival outcomes to combined temozolomide and radiotherapy. Participants will receive either temozolomide monotherapy or radiotherapy alone, depending on their biomarker status, with the aim of reducing treatment toxicity while maintaining efficacy.

Who should consider this trial

Good fit: Ideal candidates are elderly patients aged 65 and older with newly diagnosed glioblastoma and a Karnofsky Performance Status (KPS) of 60-70.

Not a fit: Patients with good performance status or those not meeting the age and diagnosis criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could offer a safer and more effective treatment option for elderly glioblastoma patients with poor performance status.

How similar studies have performed: While there is limited data on this specific biomarker-guided approach, similar strategies in treating glioblastoma have shown promise in other studies.

Eligibility criteria

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 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).
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. Serum creatinine ≤ 1.5 times ULN or 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. Negative MGMT promoter methylation status, or a status of not reportable.
2. Recurrent malignant gliomas
3. Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3 years.
4. Prior head or neck RT (except for T1 glottic cancer), or systemic therapy precluding delivery of concurrent and adjuvant temozolomide
5. Treatment with any other therapeutic clinical protocol within 30 days prior to study registration or during participation in the study.
6. 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

Where this trial is running

Calgary, Alberta and 1 other locations

• Arthur J.E. Child Comprehensive Cancer Center (formerly Tom Baker Cancer Centre) — Calgary, Alberta, Canada (Terminated)
• Cross Cancer Institute — Edmonton, Alberta, Canada (Recruiting)

Conditions Glioblastoma Multiforme