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

TheraSphere™ Y-90 Glass Microspheres are a targeted cancer therapy consisting of tiny glass beads containing radioactive Yttrium-90 (Y-90), which are injected directly into the blood vessel feeding the tumor through a microcatheter using advanced imaging guidance. The glass microspheres enter the tumor's blood supply, lodge within the blood vessels feeding the tumor, and release radiation to the tumor. The radiation works to destroy the tumor cells from within, thus limiting radiation exposure to surrounding normal tissues, a process referred to as selective internal radiation therapy (SIRT).

This study aims to investigate the maximum safe radiation dose of TheraSphere Prostate Cancer (PCa) device that can be delivered in patients with clinically localized prostate cancer. The study will also evaluate the full safety profile, technical feasibility, efficacy, and quality of life metrics of the TheraSphere PCa device.

Participants will be asked to complete the following:

• At least two image-guided visits, including a mapping assessment (without Technetium Tc albumin aggregated [Tc-MAA]) prior to treatment
• One treatment visit, including image-guided assessments
• Fifteen post-treatment follow-up visits for a total of approximately 20 visits over the 5-year study period

Note: the VOYAGER Study is a staged investigational device exemption (IDE) study; therefore, the full enrollment of 21 to 36 subjects is subject to FDA approval following safety review of the first 10 subjects enrolled.

Inclusion criteria

• 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

Exclusion criteria

• Direct evidence of regional or distant metastases after appropriate staging studies per NCCN guidelines (v03.2022)
• Histological evidence of intraductal features
• Previous treatments (pelvic radiotherapy, surgery, prostate artery embolization [PAE], transurethral resection of the prostate [TURP] or previous/ planned hormonal therapy
• 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 significant rectal surgery (haemorrhoidectomy is acceptable)
• 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
• Hip prosthesis
• 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
• 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