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

Cancer Clinical Trial

— VOYAGER  

Official title:

An Early Feasibility Study to Evaluate the Safety of the TheraSphere Prostate Cancer (PCa) Device in Patients With Clinically Localized Prostate Cancer

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT06192758
• Other study ID #: S2493
• Status: Suspended
• Phase: N/A
• Start date: April 15, 2024
• Est. completion date: August 2032

Study information

• Verified date: May 2024
• Source: Boston Scientific Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 36
• Est. completion date: August 2032
• Est. primary completion date: November 2027
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 50 Years and older

Eligibility

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. International Prostate Score Symptom (I-PSS) = 18

6. 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])

7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

8. 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

9. 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

10. 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 extra-prostatic tissues 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

Related Conditions & MeSH terms

• Cancer
• Prostate
• Prostatic Neoplasms

Intervention

Device:
• TheraSphere PCa
Single session treatment of TheraSphere PCa - Yttrium-90 Glass Microspheres for the treatment of prostate cancer. Dose vials will be available in activity ranging from 0.1 GBq (2.7 mCi) to 3 GBq (81 mCi).

Locations

Country	Name	City	State
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Ronald Reagan UCLA Medical Center (UCLA Health, Los Angeles)	Los Angeles	California
United States	University of Miami (Sylvester Comprehensive Cancer Center)	Miami	Florida
United States	Mount Sinai Hospital	New York	New York
United States	Weill Cornell Medicine	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Boston Scientific Corporation

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Prostatic imaging assessment	• Qualitative analysis of multi-parametric MRI (mp-MRI) and PI-RADS score	Through 5 years post-treatment
Primary	Maximum tolerated radiation dose of TheraSphere PCa	• The Maximum Tolerated Dose (MTD) of Yttrium-90 Glass Microspheres (TheraSphere™ PCa) is based on rate of dose limiting toxicity (DLT) through 90 days, defined as any = grade 3 adverse event (AE) according to CTCAE v.5	Through 90 days post-treatment
Secondary	Incidence of adverse events (AEs)	The following AEs/SAEs will be assessed in accordance with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0: Rate of any = grade 3 AEs; Rate of AEs of interest, i.e., any = Grade 2 GI/GU and erectile dysfunction toxicities; Rate of any treatment-emergent AEs and treatment-emergent SAEs; Rate of any treatment-related AEs and treatment-related SAEs; AEs related to non-target TheraSphere PCa distribution	Through 5 years post-treatment (acute = 90 days and late > 90 days)
Secondary	Rate of success of delivering intended dose	• The ability to deliver the intended TheraSphere PCa absorbed dose (+/- 20%) to the treatment volume based on post-treatment PET derived absorbed dose.	Immediately post-treatment
Secondary	Recurrence Free Survival	• Biochemical Recurrence Free Survival (bRFS) based on PSA according to the Phoenix criteria (RTOG-ASTRO definition). Biochemical recurrence of prostate cancer after curative treatment is defined as a PSA rise of = 2 ng/mL above the post-treatment nadir.	Through 5 years post-treatment
Secondary	Progression free survival (PFS)	• Progression free survival (PFS) and local progression free survival (LPFS), defined as time from inclusion until one of the following events, whichever comes first: biochemical progression (Phoenix criteria) or clinical progression.	Through 5 years post-treatment
Secondary	Prostate cancer specific survival	• Prostate cancer specific survival will be measured as the number of days between treatment with TheraSphere PCa and death by prostate cancer.	Through 5 years post-treatment
Secondary	Overall survival (OS)	• OS will be measured as the number of days between treatment with TheraSphere PCa and death by any cause.	Through 5 years post-treatment
Secondary	Rate of subsequent prostate anticancer treatment	• A summary table with number of subjects (%) who received subsequent definitive or systematic therapy and type of therapies received will be presented.	Through 5 years post-treatment
Secondary	Rate of histopathological recurrence	• Rate of recurrence based on histopathological assessment of prostate MR/US-fusion biopsy in patients with evidence of progression.	Through 5 years post-treatment
Secondary	Quality of Life (QoL) measured by EPIC-26	• Change from baseline measured through Expanded Prostate Cancer Index Composite (EPIC-26).	Through 5 years post-treatment
Secondary	Quality of Life (QoL) measured by MSHQ	• Change from baseline measured through Male Sexual Health Questionnaire (MSHQ).	Through 5 years post-treatment
Secondary	Quality of Life (QoL) measured by I-PSS	• Change from baseline measured through International Prostate Symptom Score (I-PSS).	Through 5 years post-treatment
Secondary	Maximum urinary flow (Qmax)	• Change from baseline	Through 5 years post-treatment
Secondary	Post-void residual (PVR) urine test	• Change from baseline	Through 5 years post-treatment
Secondary	Dose Distribution	• Dose Volume Histogram (DVH) and evaluation of D90 from post-treatment Y90 PET-MRI/CT.	Through one-week post-treatment