A Study of 177Lu-PSMA-617 in People With Gliomas

Inclusion Criteria: * Confirmed histologic diagnosis of a 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 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 * ECOG ≤ 2 * Serum creatinine level \< 1.5 x ULN or EGFR \> 60 mL/min * Liver laboratory values: ALT and AST ≤ 2.5 x ULN; Albumin \> 2 g/ dL; Bilirubin \< 3 X ULN * Normal organ and marrow function as defined as the following * Total white blood count \> 3.0 K/mcL * ANC ≥ 1.5 K/mcL * Platelets ≥ 100 K/mcL * Hemoglobin ≥ 9 g/dL * Adequate contraception prior to registration (see section 9.0) * 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 RT to \> 25% of the skeleton or prior exposure to prior Radium223, Strontium89 or 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/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 68Ga-PSMA-11/177Lu-PSMA-617 or its inactive compounding components * Current or planned pregnancy * Refusal to comply with detailed contraception requirements