Clinical trial NCT06192758: Dose Escalation Study Evaluating Safety of TheraSphere Prostate Cancer (PCa) Device
Official title: An Early Feasibility Study to Evaluate the Safety of the TheraSphere Prostate Cancer (PCa) Device in Patients With Clinically Localized Prostate Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Prostate
Cancer
Keywords: Radiation
TheraSphere
Y90
Yttrium-90
Glass
Microspheres
Lead sponsor: Boston Scientific Corporation
Sponsor class: INDUSTRY
First posted: 2024-01-05
Enrollment: 36
Sex: MALE
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Subjects will be treated in cohorts at three sequential target absorbed radiation dose levels, where the dose level for the next cohort will be determined by a prespecified decision tree for escalation/de-escalation, according to the accelerated Time-to-Event Bayesian Optimal Interval Design (TITE-BOIN) approach.

* Cohort size = 3 subjects
* ≤15 subjects (or 5 cohorts) will be treated at any single dose level. ≤ 36 subjects (or 12 cohorts) will be treated in total across all doses. If no dose limiting toxicities are observed at any dose level, a minimum of 21 subjects will be treated
Primary purpose: OTHER

Brief summary: The VOYAGER Study is an interventional, non-randomized, single-arm, dose escalation trial with the goal of determining the safety of TheraSphere PCa device in patients with clinically localized prostate cancer across US-based centers.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. 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.
3. 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):

     1. cT2b-cT2c
     2. Grade Group 2 or 3
     3. PSA 10-20 ng/mL
   * ii. Grade Group 1 or 2
   * iii. \<50% biopsy cores positive (e.g., \<6 of 12 cores)
4. Staging MRI must confirm American Joint Committee on Cancer (AJCC, 8th edition) stage T1, T2a, T2b or T2c.
5. Whole prostate gland volume ≥ 60 cc (measured on MRI)
6. International Prostate Score Symptom (I-PSS) ≤ 18
7. 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 \[brachytherapy/external beam radiation therapy\])
8. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
9. 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
10. 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
11. 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:

1. Direct evidence of regional or distant metastases after appropriate staging studies per NCCN guidelines (v03.2022)
2. Histological evidence of intraductal features
3. Previous treatments (pelvic radiotherapy, surgery, prostate artery embolization \[PAE\], transurethral resection of the prostate \[TURP\] or previous/ planned hormonal therapy
4. History of Crohn's Disease, ulcerative colitis, or ataxia telangiectasia, current gross haematuria, or current urinary catheter
5. Subjects with ongoing urinary tract infection, prostate abscess, prostatitis, or neurogenic bladder
6. Prior significant rectal surgery (haemorrhoidectomy is acceptable)
7. 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
8. Hip prosthesis
9. 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
10. 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

Primary outcomes:
measure: Maximum tolerated radiation dose of TheraSphere PCa
timeFrame: Through 90 days post-treatment
Secondary outcomes:
measure: Incidence of adverse events (AEs)
timeFrame: Through 5 years post-treatment (acute ≤ 90 days and late > 90 days)
measure: Rate of success of delivering intended dose
timeFrame: Immediately post-treatment
measure: Recurrence Free Survival
timeFrame: Through 5 years post-treatment
measure: Progression free survival (PFS)
timeFrame: Through 5 years post-treatment
measure: Prostate cancer specific survival
timeFrame: Through 5 years post-treatment
measure: Overall survival (OS)
timeFrame: Through 5 years post-treatment
measure: Rate of subsequent prostate anticancer treatment
timeFrame: Through 5 years post-treatment
measure: Rate of histopathological recurrence
timeFrame: Through 5 years post-treatment
measure: Quality of Life (QoL) measured by EPIC-26
timeFrame: Through 5 years post-treatment
measure: Quality of Life (QoL) measured by MSHQ
timeFrame: Through 5 years post-treatment
measure: Quality of Life (QoL) measured by I-PSS
timeFrame: Through 5 years post-treatment
measure: Maximum urinary flow (Qmax)
timeFrame: Through 5 years post-treatment
measure: Post-void residual (PVR) urine test
timeFrame: Through 5 years post-treatment
measure: Dose Distribution
timeFrame: Through one-week post-treatment
Other outcomes:
measure: Prostatic imaging assessment
timeFrame: Through 5 years post-treatment
Locations:
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center (UCLA Health, Los Angeles)
state: California
city: Miami
country: United States
facility: University of Miami (Sylvester Comprehensive Cancer Center)
state: Florida
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
Study officials:
affiliation: Northwestern Medical Hospital
name: Samdeep Mouli, M.D., M.S.
role: PRINCIPAL_INVESTIGATOR
affiliation: Westchester Medical Center
name: Mark Hurwitz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mouli SK, Raiter S, Harris K, Mylarapu A, Burks M, Li W, Gordon AC, Khan A, Matsumoto M, Bailey KL, Pasciak AS, Manupipatpong S, Weiss CR, Casalino D, Miller FH, Gates VL, Hohlastos E, Lewandowski RJ, Kim DH, Dreher MR, Salem R. Yttrium-90 Radioembolization to the Prostate Gland: Proof of Concept in a Canine Model and Clinical Translation. J Vasc Interv Radiol. 2021 Aug;32(8):1103-1112.e12. doi: 10.1016/j.jvir.2021.01.282. Epub 2021 Apr 9.
citation: Yuan Y, Lin R, Li D, Nie L, Warren KE. Time-to-Event Bayesian Optimal Interval Design to Accelerate Phase I Trials. Clin Cancer Res. 2018 Oct 15;24(20):4921-4930. doi: 10.1158/1078-0432.CCR-18-0246. Epub 2018 May 16.