An Optimization Study Evaluating Safety and Efficacy of the Y-90 Glioblastoma (GBM) Device in Patients With Recurrent GBM

Prior treatment

• Have received more than 1 course of prior cerebral radiotherapy (EBRT)
• Prior cranial radiation dose ≥ 66 Gy
• Have received radiosurgery, brachytherapy, or hypofractionated radiotherapy
• Have received more than 2 systemic anti-tumor treatment protocols (lines of treatment), not including neoadjuvant or adjuvant temozolomide (oral or IV)
• Have received more than 2 surgical GBM-related procedures
• Are at increased risk of wound dehiscence by the discretion of the investigators (e.g. recent brain surgery, poor skin condition, and/or previously infected surgical field or any other condition that is of increased infectious risk in the opinion of the treatment team)
• Patients with a history of an active other malignancy within 1 year prior to index procedure. NOTE: Exceptions to this requirement include adequately treated non-melanoma skin cancer or carcinoma in situ without evidence of disease
• Subject is currently participating, or plans to participate in, another investigational trial that may confound the results of this trial (unless written approval is received from the Boston Scientific study team).

Other illness

• Have leptomeningeal disease or other primary malignancy metastatic to the brain
• Patients with a history of stroke, ischemic cerebral disease, and/or at risk of cerebral herniation
• Have uncontrolled epilepsy
• Have severe and/or insufficiently controlled intercurrent illness; patients with the following are not eligible:
  • Hypertension grade 3 or higher without adequate control on medications
  • Symptomatic or unstable cardiac disease,
  • Ongoing or active bacterial or viral infection requiring systemic treatment (including HIV)
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Peripheral Neuropathy ≥ grade 1
  • Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints
• Known history of severe uncorrectable reactions to iodinated and/or gadolinium-based contrast
• Angiographic Criteria: Patients with evident AV shunting, vascular disease or tortuosity precluding safe or feasible vascular access, or patient vasculature not conducive to delivery of the therapy on baseline imaging or angiography.

Other

• None of the following exclusion criteria can be met:
• Target lesion located in or involving the infratentorial space, thalamus, hypothalamus, internal capsule, or optic chiasma
• Medical contraindication to undergo contrast-enhanced magnetic resonance imaging (MRI)

• Subject is 18 years or older and has signed and dated the trial informed consent form (ICF)
• Life expectancy ≥ 12 weeks
• Subject is willing and able to comply with the trial testing, procedures, and follow-up schedule
• History of a histologically confirmed diagnosis of glioblastoma per 2021 WHO criteria
• Have radiographic evidence of measurable tumor progression/recurrence according to RANO 2.0 criteria
• Target lesion volume does not exceed 70 cm\^3
• Prior surgery and treatment with combination of radiotherapy and chemotherapy ± Tumor Treating Fields (Optune®)
• ECOG performance status ≤ 2
• The interval since completion of external beam cranial radiotherapy must be \> 6 months, unless there is confirmation of tumor recurrence/progression outside the previous radiation treatment field, in which case the interval since completion of cranial radiation must be at least 12 weeks
• Interval since last systemic therapy until index procedure
  • ≥ 4 weeks since last dose of temozolomide
  • ≥ 4 weeks since last dose of lomustine or other nitrosourea
  • ≥ 2 weeks since last dose of any oral targeted therapy (Tyrosine Kinase inhibitor or similar)
  • ≥ 6 weeks from last dose of last intravenous bevacizumab infusion, or other antibody-based anti VEGF therapy
  • ≥ 4 weeks since last dose of investigational agents or patient has on-going \< Grade 2 AEs related to investigational agent.
• If receiving steroids, patient should be on a stable or decreasing dose equivalent to dexamethasone ≤ 6 mg/d, for at least 7 days prior to index procedure
• Have adequate organ and bone marrow function within 14 days prior to index procedure, as defined below:
  • INR ≤ 1.5 (in absence of anticoagulation)
  • Platelets ≥ 75,000/L
  • Creatinine ≤1.5 mg/dL
  • Absolute Neutrophil Count ≥1.5 x 109/L
  • Hemoglobin ≥9.0 g/dL
• For female of child-bearing potential:
  • Have a negative pregnancy test within 14 days prior to index procedure
  • If sexually active must be using, or agree to use, an acceptable method of birth control as confirmed by the investigator for the duration of their participation in the study
  • If currently breastfeeding, must agree to stop breastfeeding
• Angiographic Criteria:
  • The intent of therapy should be to encompass the entire radiographically defined target lesion within the PV b. Each PV is ≤ 150cc, with the total PV not exceeding 400cc