A Feasibility Study to Evaluate the Safety of the TheraSphere Glioblastoma (GBM) Device in Patients With Recurrent GBM

Inclusion Criteria:

1. Subject is 18 years or older and has signed and dated the trial informed consentform (ICF)

2. Life expectancy ≥ 12 weeks

3. Subject is willing and able to comply with the trial testing, procedures, andfollow-up schedule

4. History of a histologically confirmed diagnosis of glioblastoma per 2021 WHOcriteria

5. Have radiographic evidence of tumor progression/recurrence with measurable disease (≥ 1 cm to ≤ 5cm bidirectional diameters) by contrast-enhancement on MRI, accordingto RANO criteria

6. Prior surgery and treatment with combination of radiotherapy and chemotherapy ±Tumor Treating Fields (Optune®)

7. Prior cranial radiation dose < 66 Gy

8. WHO performance status ≤ 2

9. The interval since completion of cranial radiotherapy must be > 6 months, unlessthere is tissue confirmation of tumor recurrence/progression outside the previousradiation treatment field, in which case the interval since completion of cranialradiation must be at least 12 weeks

10. Interval since last systemic therapy until presumed date of intervention ≥ 1 cycleor ≥ 2 biological half-lives, i.e.

11. ≥ 4 weeks since last dose of temozolomide

12. ≥ 6 weeks since last dose of lomustine or other nitrosourea

13. ≥ 2 weeks since last dose of a small molecule targeted agent (Tyrosine KinaseInhibitor or similar)

14. ≥ 6 weeks from last dose of last intravenous bevacizumab infusion, or otherantibody-based VEGF therapy

15. If receiving steroids, patient should be on a stable or decreasing dose equivalentto dexamethasone ≤ 6 mg/d, for at least 7 days prior to registration

16. Have adequate organ and bone marrow function within 14 days prior to registration,as defined below:

17. INR ≤ 1.2 (in absence of anticoagulation)

18. Platelets ≥ 100,000/L

19. Creatinine ≤1.5 mg/dL

20. Absolute Neutrophil Count ≥1.5 x 10^9/L

21. Hemoglobin ≥9.0 g/dL

22. Have a negative pregnancy test within 14 days prior to registration on study (forFOCBP, female of child-bearing potential)

23. Subject is a male or non-pregnant female. If female of child-bearing potential, andif sexually active must be using, or agree to use, a medically acceptable method ofbirth control as confirmed by the investigator

24. Angiographic Mapping Inclusion Criteria:

25. Accessible neurovascular anatomy that allows for safe microcatheter placement (up to two locations) to infuse TheraSphere GBM to treat all of the T1enhancing component of target lesion confirmed by neuro-interventional team.

26. Total treatment volume is ≤ 150cc as determined by multidisciplinary team.

27. Additional Inclusion Criteria:

28. Group A: perfused volume encompasses the non-dominant hemisphere andnon-eloquent regions of the brain

29. Group B: perfused volume encompasses the non-dominant hemisphere and eloquentregions of the brain

30. Group C: perfused volume encompasses the dominant hemisphere and non-eloquentregions of the brain

31. Group D: perfused volume encompasses the dominant hemisphere and eloquentregions of the brain

Exclusion Criteria:

1. Have bilateral gadolinium enhancing disease, tumor located in the posterior fossa,tumor involving critical subcortical structures (thalamus/hypothalamus, midbrain,brainstem, corticospinal tract, internal capsule, cerebral peduncle), tumorapproximating or invading the brainstem and/or optic chiasma, leptomeningealdisease, or extracranial metastatic disease

2. Have received more than 1 course of prior cranial radiotherapy (EBRT)

3. Have received radiosurgery, brachytherapy, or hypofractionated radiotherapy

4. Have received more than 2 systemic treatment protocols (lines of treatment), notincluding maintenance temozolomide

5. Have received prior intra-arterial cerebral infusion therapy

6. Have received more than 2 surgical GBM-related procedures

7. Have received prior thoracic radiation therapy

8. Are at increased risk of wound dehiscence by the discretion of the investigators (e.g. brain surgery within the last 3 months, poor skin condition, and/or previouslyinfected surgical field or any other condition that is of increased infectious riskin the opinion of the neurosurgeon)

9. Have uncontrolled epilepsy

10. Have severe and/or insufficiently controlled intercurrent illness; patients with thefollowing are not eligible:

11. Hypertension grade 3 or higher without adequate control on medications

12. Symptomatic or unstable cardiac disease, known to have right-to-left shunts, orsevere pulmonary hypertension (pulmonary artery pressure > 90 mmHg)

13. Pulmonary insufficiency (arterial oxygen pressure (Pa,O2) of < 60 mmHg, oroxygen saturation (Sa,O2) of < 90%) as measured by fingertip pulse oximeter

14. Ongoing or active bacterial or viral infection requiring systemic treatment (including HIV)

15. Pneumonitis

16. Psychiatric illness/social situations that would limit compliance with studyrequirements

17. Peripheral Neuropathy ≥ grade 1

18. Any other illness or condition that the treating investigator feels wouldinterfere with study compliance or would compromise the patient's safety, studyendpoints or longevity

19. Are currently pregnant or breast feeding (unless patient agrees to stopbreastfeeding)

20. Patients with a history of an active other malignancy within 1 year prior toregistration. NOTE: Exceptions to this requirement include adequately treatednon-melanoma skin cancer or lentigo maligna or carcinoma in situ without evidence ofdisease, or recurrent glioblastoma

21. Patients with a history of ischemic cerebral disease and/or at risk of cerebralherniation

22. Medical contraindication to undergo contrast-enhanced magnetic resonance imaging (MRI)

23. Known history of hypersensitivity reactions to iodinated and/or gadolinium-basedcontrast

24. Subject has received any other investigational agents within 4 weeks of treatment,or is currently participating, or plans to participate in, another investigationaltrial that may confound the results of this trial (unless written approval isreceived from the Boston Scientific study team)

25. Angiographic Mapping Exclusion Criteria: Patients with significant vascular disease,significant AV shunting, or anatomic tortuosity on MR/CT Angiogram precluding safeor feasible vascular access