Adjuvant 177Lu-PSMA-617 Radiopharmaceutical Therapy with Temozolomide for the Treatment of IDH Wild Type Gliomas Expressing PSMA following Standard Treatment

Inclusion Criteria

• Confirmed histologic diagnosis of a World Health Organization (WHO) grade 2-4 glioma that is IDH1 R132H-wildtype, including the following: * Diffuse astrocytoma, IDH-wildtype (grade 2-4) * Glioblastoma, IDH-wildtype * Diffuse midline glioma, H3 K27-altered * Diffuse hemispheric glioma, H3 G34-mutant * Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype
• PSMA positive pathological stain (by immunohistochemistry) of baseline (pre-radiotherapy) resection or biopsy sample
• Completion of standard of care therapy including surgery (for resectable tumors) and adjuvant external beam radiation therapy (EBRT) for glioma
• Patients must be on a dose of 4 mg or less of dexamethasone (or dexamethasone equivalent steroid) for 5 days prior to first planned dose of radiopharmaceutical
• Age ≥ 18
• Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Serum creatinine level < 1.5 x upper limit of normal (ULN) or estimated glomerular filtration rate (EGFR) > 60 mL/min
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN
• Albumin > 2 g/ dL
• Bilirubin < 3 X ULN
• Total white blood count > 3.0 K/mcL
• Absolute neutrophil count (ANC) ≥ 1.5 K/mcL
• Platelets ≥ 100 K/mcL
• Hemoglobin ≥ 9 g/dL
• Adequate contraception prior to registration
• Ability to understand, and willingness to sign the informed consent

Exclusion Criteria

• Patient known to harbor any other non-canonical IDH mutations (i.e., non-R132H)
• Target lesion within 5 mm of either the brainstem, optic chiasm or optic nerves
• Receipt of bevacizumab as part of the initial treatment for glioma
• Life expectancy less than 12 weeks
• Nonhealing wound, ulcer or bone fracture
• History of severe brain injury
• Patient not eligible for sequential MRI evaluations
• Patients with prior radiation therapy (RT) to > 25% of the skeleton or prior exposure to prior radium Ra 223 (Radium223), strontium Sr-89 (Strontium89) or samarium Sm-153 (Samarium153) containing compounds
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
• Patients with known or suspected history of grade II or higher chronic kidney disease (CKD)
• Unable to tolerate the PSMA PET/magnetic resonance (MR) or PSMA PET/CT
• History of viral hepatitis or chronic liver disease with active symptoms
• History of pituitary or adrenal dysfunction
• Previously diagnosed active infection (e.g., human immunodeficiency virus [HIV] or viral hepatitis)
• Any condition that in the opinion of the investigator, would preclude participation in this study
• Receipt of any other investigational agents or participation in a concurrent treatment protocol
• Known allergies, hypersensitivities, or intolerance to gallium Ga 68 gozetotide (68Ga-PSMA-11)/177Lu-PSMA-617 or its inactive compounding components
• Current or planned pregnancy
• Refusal to comply with detailed contraception requirements