Azeliragon and Chemoradiotherapy in Newly Diagnosed Glioblastoma

Prior treatment

• Patients who have had treatment with any investigational cancer drug prior to the first dose of study treatment.
• Patients receiving CYP2C8 inhibitors
• Patient is unwilling or unable to comply with study procedures, including, but not limited to self-administration of oral medication.
• Patients with concurrent participation in another interventional clinical trial or use of another investigational agent within 14 days of starting azeliragon. Patients who are participating in non-interventional clinical trials (e.g., QOL, imaging, observational, follow-up studies, etc.) are eligible, regardless of the timing of participation.

Other illness

• Patients with a serious active infection (such as a wound infection requiring parenteral antibiotics) at the time of inclusion or other serious underlying medical conditions that would impair the ability of the patient to receive protocol treatment
• Patients with any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol.
• Patients with a gastrointestinal condition that could interfere with swallowing or absorption.

Age

• Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for \> 5 years

Other

• Patient has experienced an increase of ECOG to \> 2 between Screening and the time of first dose with azeliragon.
• Females of childbearing potential who are sexually active or males with female partners of childbearing potential, where either the female or the male is unwilling to use a highly effective method of contraception during the trial and for 6 months after the last administration of azeliragon.

• Patient must have histologically confirmed newly diagnosed glioblastoma (GBM, world health organization (WHO) grade IV). The histological diagnosis must have been made after biopsy or neurosurgical tumor resection.
  • Note: Patients should be isocitrate dehydrogenase (IDH) wild type diagnosed locally
• The local O-6-Methylguanine-DNA Methyltransferase (MGMT) report determination should be available and should be uploaded to the electronic case report form (eCRF).
• Patient should have had a gross total or subtotal resection performed \< 7 weeks prior to enrollment, documented at postoperative MRI. Patients who have had a biopsy only without resection are not eligible.
• Patient deemed suitable by the treating physician to receive the standard radiotherapy regimen in combination with temozolomide.
• Male or non-pregnant and non-lactating female and ≥ 18 to ≤ 70 years of age.
• Patient may have received and continue to receive corticosteroids, but must be on a stable or decreasing dose for at least 14 days prior to first dose of study treatment.
• Patient has not received prior chemotherapy or radiotherapy.
• Patient has adequate biological parameters as demonstrated by the following blood counts at Screening (obtained ≤ 14 days prior to enrollment) and at Baseline-Day 0: Absolute neutrophil count (ANC) ≥ 1.0 × 109/L; Platelet count ≥ 75,000/mm3 (75 × 109/L); Hemoglobin (Hgb) ≥ 9 g/dL without transfusion or growth factor support
• Patient has the following blood chemistry levels at Screening (obtained ≤ 14 days prior to enrollment) and at Baseline-Day 0:
  • aspartate amino-transferase (AST)(SGOT), alanine transferase (ALT)(SGPT) ≤ 2.5 × upper limit of normal range (ULN). Total bilirubin ≤ 1.5 × ULN.
  • Estimated creatinine clearance of \> 60 mL/min (per Cockcroft -Gault formula)
• Patients with a QTC of ≤ 480 msec
• Patient has ECOG performance status of ≤ 2
• Patient has been informed about the nature of the study, and has agreed to participate in the study, and signed the Informed Consent Form (ICF) prior to participation in any study-related activities.