Daily temozolomide for older adults with newly diagnosed glioblastoma and unmethylated MGMT promoter

Daily Temozolomide for Elderly Patients With Unmethylated MGMT- Promoter Newly Diagnosed GliOblatoma

This trial will test whether a modified daily temozolomide schedule helps people aged 65 and older with newly diagnosed glioblastoma whose tumors have an unmethylated MGMT promoter.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 118 (estimated)
• Ages: 65 Years and up
• Sex: All
• Sponsor: Sunnybrook Health Sciences Centre (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Toronto, Ontario)
• Trial ID: NCT07476794 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional trial gives a modified daily temozolomide regimen to patients aged 65 or older who have newly diagnosed WHO grade 4, IDH wild-type glioblastoma with an unmethylated MGMT promoter. Participants must have completed 40 Gy in 15 fractions with concurrent temozolomide within six weeks before enrollment. The study monitors safety, tolerability, clinical status, laboratory tests, and brain imaging while patients receive the daily dosing schedule. Key outcomes include treatment-related adverse events, progression-free survival, and overall survival.

Who should consider this trial

Good fit: Ideal candidates are adults aged 65 or older with newly diagnosed WHO grade 4 IDH wild-type glioblastoma, an unmethylated MGMT promoter, ECOG performance status 0–2 and KPS ≥60 who completed 40 Gy in 15 fractions with concurrent temozolomide within the prior six weeks and have adequate organ function.

Not a fit: Patients with MGMT-methylated tumors, IDH-mutant gliomas, poor performance status or organ dysfunction, those who did not receive the specified short-course radiation with concurrent temozolomide, or who cannot travel to the study site are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the modified daily temozolomide schedule could slow tumor progression and extend survival for older patients whose tumors are less likely to respond to standard temozolomide dosing.

How similar studies have performed: Standard temozolomide has shown limited benefit for unmethylated MGMT glioblastoma, and alternative temozolomide schedules have been tested with mixed results, so this approach is experimental rather than proven.

Eligibility criteria

Inclusion Criteria:

* Age ≥65 years.
* Histopathologically confirmed newly diagnosed WHO grade 4, IDH wild-type GBM
* Unmethylated MGMT promoter, according to local assessment
* Completed treatment with 40 Gy in 15 fractions over three weeks, with concurrent TMZ, within six weeks prior to enrollment
* Eastern Cooperative Oncology Group (ECOG) performance status scale of 0, 1, or 2.
* Karnofsky Performance Status (KPS) ≥60.
* Adequate organ function, as defined by the following laboratory values obtained within 28 days prior to enrollment:

  * Absolute neutrophil count (ANC) \>1.5 × 10⁹/L (1,500 cells/mm³).
  * Platelet count \>100 × 10⁹/L (100,000 cells/mm³).
  * Serum creatinine \<1.5 times the upper limit of normal.
  * Total serum bilirubin \<1.5 times the upper limit of normal.
  * ALT (SGPT) \<2.5 times the upper limit of normal and/or AST (SGOT) \<2.5 times the upper limit of normal.
* Signed informed consent (and assent, if applicable) must be obtained from the participant or their legal representative, ensuring the participant's ability to adhere to the study requirements.

Exclusion Criteria:

* Diffuse leptomeningeal involvement at the time of diagnosis.
* Inability to undergo contrast-enhanced magnetic resonance imaging (MRI)
* Known hypersensitivity to TMZ components or Dacarbazine
* Severe myelosuppression
* Active hepatitis B infection
* Severe or uncontrolled medical conditions (e.g., active systemic infection, diabetes, hypertension, coronary artery disease, or psychiatric disorders) that, in the investigator's judgment, could compromise patient safety or impede study completion.
* History of prior or second invasive malignancy, except for:

  * Non-melanoma skin cancer.
  * Completely resected cervical carcinoma in situ.
  * Low risk prostate cancer or under active surveillance.
  * Other cancers for which the subject has completed potentially curative treatment more than 3 years prior to study entry are allowed.

Where this trial is running

Toronto, Ontario

• Sunnybrook Health Sciences Centre — Toronto, Ontario, Canada (Recruiting)

Conditions Glioblastoma