Comparison of Cerebraca Wafer Plus Temozolomide Versus Temozolomide Alone in Recurrent Glioblastoma

Inclusion criteria

, subjects must meet all following criteria for study enrollment:

• Subject must be aged ≥ 18, regardless of gender
• Subject must have histologically confirmed glioblastoma with:

• Completed first-line therapy including surgery plus temozolomide and radiation (concurrent temozolomide/radiation)
• Current presentation being first or second recurrence only
• Subject must have measurable disease preoperatively with at least one contrast-enhancing MRI-identified lesion measuring ≥ 1 cm in two perpendicular dimensions per RANO 2.0 criteria
• Subject must be deemed eligible for gross total resection of contrast-enhancing MRI-identified lesion by neurosurgeon's pre-operative assessment, according to RANO II
• Subject must have Karnofsky Performance Status (KPS) ≥ 70
• Subject must have recovered from prior therapy toxicities with adequate organ function:

• Hemoglobin ≥ 8 g/dL
• Platelets ≥ 100,000/mm3
• White blood cell count (WBC) ≥ 3,000 cells/mm3
• Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
• Absolute lymphocyte count (ALC) ≥ 1,000 cells/mm3
• Coagulation tests (prothrombin time [PT], activated partial thromboplastin time [APTT], International Normalized Ratio [INR]) ≤ 1.5 × ULN
• Total bilirubin (TBIL) < 3 × ULN
• Alkaline phosphatase (ALP) ≤ 3 × ULN and/or Gamma glutamyltransferase (GGT) ≤ 1.5 × ULN
• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and/or Alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≤ 3 x ULN
• eGFR ≥ 30 mL/min (MDRD formula)
• QTc interval: msec ≤ 450 (males) or 470 (females) (Fridericia's formula: QTc=QT/RR(1/3); RR=RR interval)

Exclusion criteria

, subjects with any of the following will be excluded:

• Histological confirmation of oligodendroglioma or mixed glioma
• Presence of IDH or H3K27M mutation, or 1p19q co-deletion
• MRI-identified lesion meeting any criteria:

• Multi-focal (defined as 2 non-contiguous contrast enhancement areas > 1 cm in 2 planes on fluid-attenuated inversion recovery, FLAIR or T2-weighted sequences)
• Presence of diffuse subependymal or leptomeningeal dissemination
• Contrast-enhancing lesion > 6 cm in any dimension
• Tumor location unsuitable for surgical resection and Cerebraca Wafer implantation in the brain areas where surgical intervention would cause significant neurological deficits
• Prior bevacizumab treatment with uncontrollable tumor progression
• History of other malignancy within past 5 years
• Immunocompromised status or autoimmune conditions requiring systemic immunosuppressive therapy, with the following exceptions:

• Patients with autoimmune conditions may be eligible after individual assessment of the condition, its severity, and potential interaction with the Cerebraca Wafer.
• Patients with HIV infection are eligible if they:

i. Have CD4+ T-cell counts ≥350 cells/μL ii. Are on stable anti-retroviral therapy iii. Have HIV viral load below the limit of quantification c. Patients with HBV infection are eligible if they: i. Are on appropriate suppressive anti-viral therapy prior to study enrollment ii. Have no evidence of hepatic decompensation d. Patients with history of HCV infection are eligible if they: i. Have completed curative anti-viral treatment with HCV viral load below the limit of quantification

• Active, uncontrolled infection or medical condition that could compromise safety and efficacy assessment