Dose Escalation Study Evaluating Safety of TheraSphere Prostate Cancer (PCa) Device

Prior treatment

• Previous treatments (pelvic radiotherapy, surgery, prostate artery embolization \[PAE\], transurethral resection of the prostate \[TURP\] or previous/ planned hormonal therapy
• Prior significant rectal surgery (haemorrhoidectomy is acceptable)

Other illness

• History of Crohn's Disease, ulcerative colitis, or ataxia telangiectasia, current gross haematuria, or current urinary catheter
• Subjects with ongoing urinary tract infection, prostate abscess, prostatitis, or neurogenic bladder
• Prior invasive malignancy unless disease free for a minimum of 3 years. Exceptions to this requirement include adequately treated non-melanoma skin cancer or lentigo maligna or carcinoma in situ without evidence of disease
• Medical contraindication to undergo contrast-enhanced angiography, CT scan and magnetic resonance imaging (MRI), or arterial catheterization, or known history of hypersensitivity reactions to iodinated and gadolinium-based contrast product

Other

• Direct evidence of regional or distant metastases after appropriate staging studies per NCCN guidelines (v03.2022)
• Histological evidence of intraductal features
• Hip prosthesis
• Angiographic exclusion criteria:
  • a. Perfusion to tissues outside the Planning Target Volume (PTV) that cannot be corrected by placement of the catheter distal to collateral vessels or the application of standard angiographic techniques, such as coil embolization
  • b. Type V prostatic artery origin on either side

• Subject has ability to comprehend and willingness to sign and date the IRB-approved study informed consent form (ICF), and to comply with the study testing, procedures, and follow-up schedule.
• Histologic confirmation of adenocarcinoma of the prostate by MR-fusion biopsy. Referral biopsy for eligibility must be completed between 180 days and 6 weeks prior to mapping procedure.
• Subject with favorable intermediate risk clinically localized prostate cancer defined per NCCN Guidelines version 3.2022 as follows:
  • Favorable intermediate-risk has all the following:
  • i. One Intermediate Risk Factor (IRF):
  • cT2b-cT2c
  • Grade Group 2 or 3
  • PSA 10-20 ng/mL
  • ii. Grade Group 1 or 2
  • iii. \<50% biopsy cores positive (e.g., \<6 of 12 cores)
• Staging MRI must confirm American Joint Committee on Cancer (AJCC, 8th edition) stage T1, T2a, T2b or T2c.
• Whole prostate gland volume ≥ 60 cc (measured on MRI)
• International Prostate Score Symptom (I-PSS) ≤ 18
• Estimated life expectancy of \>5 years according to NCCN guideline's tools (NCCN v03.2022) who has declined or is ineligible for Standard of Care treatments (observation, active surveillance, surgery, and radiation therapies \[brachytherapy/external beam radiation therapy\])
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
• Angiographic inclusion criteria:
  • a. Type I to IV prostate artery origins on both hemiglands.1
  • b. No evidence of procedure limiting vascular abnormalities (aneurysms, stenosis, shunt, fistula, occlusion) or morphologic asymmetric single prostate artery on either side (hemigland)
  • c. Bilaterally accessible solitary prostatic arteries.
  • d. Complete perfusion of the prostate gland via a single dominant vessel for each hemigland
• Have adequate organ and bone marrow function within 30 days prior to index procedure, as defined below:
  • a. International Normalized Ratio (INR) ≤ 1.2 (in absence of anticoagulation)
  • b. Platelets ≥ 75,000/L
  • c. GFR ≥ 40 mL/min/1.73m2
  • d. Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
  • e. Hemoglobin (Hgb) ≥ 9.0 g/dL (Note: the use of transfusion or other intervention to achieve adequate bone marrow function is acceptable
  • f. ALT/AST ≤ 5 x upper limit of normal (ULN)
  • g. Bilirubin ≤ 2 mg/dL
• Patients with known Human Immunodeficiency Virus (HIV) infection are eligible with well controlled HIV infection, no current or previous AIDS-related complications and CD4+ T-cell (CD4+) counts ≥ 350 cells/uL