Liposomal Rhenium Re 186 in Treating Patients with Recurrent Glioblastoma

Inclusion Criteria

• At least 18 years of age
• Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator’s Institutional Review Board (IRB)/Ethics Committee
• For the Phase 1, histologically confirmed Grade III/IV recurrent Glioma (following 2021 World Health Organization [WHO] CNS5 glioma nomenclature, e.g., Astrocytoma, IDH-mutant grade 3 or 4; Glioblastoma, IDH-wildtype grade 4). For the Phase 2, histologically confirmed Glioblastoma (following 2021 WHO CNS5 nomenclature) * For the Phase 1, any number of recurrences may be included * For the Phase 2, limited to 1 recurrence
• Progression by RANO criteria or other clinically accepted neurooncology evaluation, following standard treatment options with known survival benefit (for any recurrence (e.g., surgery, temozolomide, radiation, and tumor treating fields [unless). Patient may be included in study if medically unable or unwilling]) to follow standard treatment options for any recurrence
• Patients who receive treatment with antiepileptic medications must have a two week history of stable dose of antiepileptic without seizures prior to study start (dosing)
• Patients with corticosteroid requirements to control cerebral edema must be maintained at a stable or decreasing dose for a minimum of two weeks without progression of clinical symptoms prior to study start (dosing)
• A volume of enhancing tumor which falls within the treatment field volume being evaluated in the respective phase/cohort. For Phase 2 only, tumor sizes are limited to =< (less than or equal to) 20 cm^3
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2; Karnofsky Performance Status >= 60
• Life expectancy of at least 2 months
• Bilirubin =< 1.5 times upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 times upper limit of normal (ULN)
• Serum creatinine =< 1.5 x ULN
• Absolute neutrophil count (ANC) >= 1000 cells/uL (without hematologic support)
• Platelet count >= 100,000/uL (without hematologic support)
• Hemoglobin >= 9.0 g/dL (without hematologic support)
• All women of childbearing potential must have a negative serum pregnancy test and male and female subjects must agree to use effective means of contraception (for example, surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an intrauterine device [IUD]) with their partner from entry into the study through 6 months after the last dose
• PART 2: Bevacizumab naive glioblastoma with no more than 1 recurrence

Exclusion Criteria

• The subject has evidence of acute intracranial or intratumoral hemorrhage either by magnetic resonance imaging (MRI) or computerized tomography (CT) scan; subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin are eligible
• The subject is unable or contraindicated to undergo MRI scan (e.g., has pacemaker or medically unstable)
• The subject has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) v4.0 Grade =< 1 from AEs (except alopecia, anemia, and lymphopenia) due to antineoplastic agents, investigational drugs, or other medications that were administered prior to study
• The subject is pregnant or breast-feeding
• The subject has serious intercurrent illness as determined by the treating physician, that would compromise either patient safety or study outcomes such as: * Hypertension (two or more blood pressure readings performed at screening of > 150 mmHg systolic or > 100 mmHg diastolic) despite optimal treatment * Active medically significant infection unresponsive to antibiotics (e.g., non-healing wound, ulcer), uncontrolled systemic infection, or bone fracture * Clinically significant cardiac arrhythmias not controlled by appropriate medications * Untreated hypothyroidism * Symptomatic congestive heart failure or unstable angina pectoris within 3 months of study start (dosing) * Myocardial infarction, stroke, or transient ischemic attack within 6 months of study start (dosing) * Known active malignancy (other than glioma) except non-melanoma skin cancer or carcinoma in-situ in the cervix unless primary investigator (PI) determines it would not impact patient safety or efficacy determinations
• The subject has inherited bleeding diathesis or coagulopathy with the risk of bleeding
• The subject has received any of the following prior anticancer therapy: * Prior treatment with bevacizumab * Non-standard radiation therapy such as brachytherapy, systemic radioisotope therapy, or intra-operative radiotherapy (IORT) to the target site * Radiation therapy within 12 weeks of screening * Systemic therapy or non-cytotoxic hormonal therapy (e.g., tamoxifen) within 14 days or 5 half-lives, whichever is shorter, of study start (dosing) * Biologic agents (antibodies, immune modulators, vaccines, and cytokines) within 21 days prior of study start (dosing) * Nitrosoureas or mitomycin C within 42 days of study start (dosing) * Metronomic/protracted low-dose chemotherapy within 14 days of study start (dosing) * Other cytotoxic chemotherapy within 28 days of study start (dosing) * Prior treatment with carmustine wafers * Investigational agents within 28 days of study start (dosing)
• Multifocal progression or involvement of the leptomeninges
• Psychiatric illness/social situations that would limit compliance with the study requirements
• Infratentorial disease
• The subject has a tumor located within 1-2 cm of a ventricle AND it is determined by the surgeon, PI, and sponsor to be a risk for drug extravasation to the subarachnoid space if given catheter placement and drug administration