Biomarker-guided RAdiation-deferring Treatment in Younger GBM Patients - Pilot Study

Prior treatment

• Prior radiation or systemic treatment for glioblastoma
• Diagnostic biopsy/craniotomy more than 2-weeks prior to study screening such that insufficient time for molecular profiling
• Prior radiation or systemic treatment for glioblastoma
• Placement of Gliadel wafers or receipt of any other local investigational therapy at the time of surgery
• Prior radiation or systemic anti-cancer treatment for glioblastoma or any glioma, including a history of lower grade glioma
• Placement of Gliadel wafers or receipt of any other local investigational therapy at the time of surgery
• Any significant concomitant disorder, including active bacterial, fungal, or viral infection, incompatible with participation in the study
• Clinically significant gastrointestinal disorder that is expected to compromise absorption of oral medication, as determined by the treating physician for those receiving toral therapy

Other illness

• Multi-focal disease not likely to be encompassed within a standard radiotherapy field, infratentorial disease or leptomeningeal disease
• Evidence of significant acute intracranial or intra-tumoural haemorrhage either by magnetic resonance imaging (MRI) or computerized tomography (CT) scan.
• Serious intercurrent illness, as determined by the treating physician, that would compromise either patient safety or study outcomes.
  • Key Eligibility Criteria (Post-Operative Screening)
• Multi-focal disease not encompassed within a standard radiotherapy field, infratentorial disease or leptomeningeal disease
• Evidence of significant acute intracranial or intra-tumoural haemorrhage either by magnetic resonance imaging (MRI) or computerized tomography (CT) scan
• Serious intercurrent illness, as determined by the treating physician, that would compromise either patient safety or study outcomes
  • Key Eligibility Criteria (for patients being offered trial treatment)
• Multi-focal disease not encompassed within a standard radiotherapy field, infratentorial disease or leptomeningeal disease
• Evidence of significant acute intracranial or intra-tumoral haemorrhage either by magnetic resonance imaging (MRI) or computerized tomography (CT) scan as per clinician discretion. (Note: Patients with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin are not excluded).
• Known history of HIV, hepatitis B or hepatitis C
• Any serious intercurrent illness, as determined by the treating physician, that would compromise either patient safety or study outcomes
• Psychiatric illness or a social situation that would limit compliance with the study procedures requirements

Lab values

• QTc interval \> 470 milliseconds on screening ECG

Age

• History of another malignancy, except adequately treated non melanoma skin cancer or carcinoma in-situ of the cervix. Patients with prior malignancy are excluded unless they have been disease free for ≥ 2 years

Other

• Pregnant or breastfeeding at time of screening

• Adult patient who is aged 18-≤55 years of age
• Has MRI features consistent with a high-grade glioma
• Is planned for standard of care biopsy or surgery to investigate and/or treat this lesion
• ECOG 0-1
• Provides informed written consent
• Aged 18 to ≤55-years of age
• Newly diagnosed patient with IDH-wildtype glioblastoma as per WHO 2021, or morphological features consistent with glioblastoma but pending confirmatory NGS or other profiling
• ECOG 0-1
• Consents to, and has sufficient tissue, for:
• IHC for BRAF V600E, pan-TRK and MMR proteins
• Further confirmatory NGS for NTRK fusions if pan-TRK IHC is positive
• Life expectancy of at least 12 weeks
• Newly diagnosed patients with IDH-wildtype glioblastoma as per WHO 2021
• Able to provide written informed consent
• Aged 18 to ≤55-years of age
• ECOG 0-1
• Adequate organ function as defined by
  • Hepatic: total bilirubin ≤2.0 × upper limit of normal (ULN); alanine transaminase (ALT) and aspartate transaminase (AST) ≤1.5 × ULN
  • Renal: estimated glomerular filtration rate (GFR) ≥60 mL/min
  • Bone marrow: platelets ≥100 × 109/L, absolute neutrophil count (ANC) ≥1.5 × 109/L, haemoglobin ≥9 g/dL
• If the patient is a male or female with reproductive potential, the patient is willing to use an approved contraceptive method (e.g., intrauterine device \[IUD\], birth control pills, or barrier device) during and for three months after discontinuation of study drug
• If the patient is a woman of childbearing potential, she has a negative serum pregnancy test within seven days prior to study enrollment
• Life expectancy of at least 12 weeks
• Patient is on stable or reducing dose of steroid within the first week of study enrolment, not exceeding a dose of dexamethasone 2 mg or equivalent

Criteria the registry did not label

• Key Eligibility Criteria (Pre-Operative Screening)