PSMA-Guided Ablation of the Prostate (P-GAP)

PSMA-Guided Ablation of the Prostate: A Multicenter Randomized Controlled Trial

The goal of this phase 2 multicenter randomized controlled trial is to study the accuracy of second generation prostate specific membrane antigen (PSMA) positron emission tomography (PET; utilizing 18F-PSMA-1007) compared to standard of care multiparametric MRI and MRI targeted-prostate biopsy for staging in patients diagnosed with unilateral prostate cancer who are eligible for focal therapy.

The main question it aims to answer is:

Can PSMA PET improve diagnostic accuracy for the primary staging of Prostate Cancer for patients undergoing focal therapy thereby reducing residual and recurrence disease?

Participants who are eligible by current standard of care diagnostic workup will undergo 1:1 randomization to PSMA PET scan or no further imaging. Those diagnosed with bilateral disease by PSMA PET will be ineligible for focal therapy and be referred for radical therapy. Men with unilateral disease on PSMA PET and those randomized to no further imaging will then undergo focal therapy. All men undergoing focal therapy will receive PSMA PET, MRI, and combined targeted and systematic biopsy 12 months after ablation. The primary outcome will be the detection of Gleason Grade Group 2 or higher prostate cancer in men 12 months after hemigland ablation.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer; Localized Prostate Carcinoma
• Intervention / Treatment: Diagnostic test: PSMA-1007 Positron Emission Tomography (PET) scan

Detailed Description

1. Background & Rationale

   Focal therapy is emerging as a new treatment strategy for appropriately selected men with localized prostate cancer. Focal therapy (also called partial gland ablation) is the concept of treating only where the tumor is believed to be located within the prostate, leaving normal healthy regions of the prostate untreated. Thus, focal therapy minimizes treatment side effects such as erectile dysfunction and incontinence, while providing good cancer control.

   The foundation of performing oncologically sound partial gland ablation is possessing a high degree of diagnostic certainty that the tumor is limited to the region that is being treated and is not unknowingly present elsewhere in the gland. However, this is currently a major diagnostic challenge. The current diagnostic strategy for work-up of a patient for focal therapy is based on a pre-operative multiparametric MRI and combined targeted and systematic prostate biopsy showing intermediate risk prostate cancer localized to only one side of the prostate gland. This combination has been shown to accurately diagnose the final tumor grade in 96.5% of men. However, whole mount pathology data after radical prostatectomy shows that over 50% of cases that would pre-operatively have been deemed appropriate for focal therapy, which is a unilateral treatment, in fact harbour bilateral disease, which would mean that contralateral tumor would be inadvertently left untreated. Similarly, our group has shown that of the 35% of men who were found to have residual tumor after hemigland ablation of their prostate for unilateral disease, two-thirds of residual tumors were identified on the side contralateral to the ablative treatment. Therefore, our current gold standard pre-operative imaging and biopsy techniques are under staging many men who are undergoing focal therapy and a new paradigm is required to advance focal ablative treatments.

   PSMA PET is a new imaging technique that uses a radioligand that binds to prostate specific membrane antigen (PSMA). PSMA is expressed at high levels in prostate cancer and the degree of expression correlates proportionately with tumor grade. A second generation PSMA PET radioligand, called 18F-PSMA-1007, has been used extensively at our site and possesses the key attributes of minimal urinary excretion, high resolution, and a half-life that as Gallium based radioligands. This makes 18F-PSMA-1007 an excellent candidate for improving the intraprostatic diagnostic accuracy of prostate cancer localization in patients considering focal therapy as a treatment option.

2. Research Question & Objectives

   Primary outcome:

   The primary outcome is the detection of any clinically significant prostate cancer (defined as greater than or equal to Gleason Grade Group 2) at MRI-guided combined targeted and systematic biopsy 12 months after hemigland ablation.

   Secondary outcomes:

   • the number of men found to have bilateral disease on PSMA PET prior to hemi-gland ablation
   • the number of men found to have bilateral disease on PSMA PET after hemi-gland ablation
   • the rate of contralateral Gleason Grade Group 2 or greater prostate cancer at 12-month biopsy
   • the rate of contralateral Gleason Grade Group 2 or greater prostate cancer at final pathology in men undergoing radical prostatectomy after PSMA PET detected bilateral disease
   • 5-year failure free survival defined as freedom from radical or systematic therapies, metastasis, prostate cancer specific and overall survivals.
   • side effects of PSMA PET imaging
   • health economics analysis of PSMA PET prior to hemigland ablation
   • Quality of life outcomes will be assessed with validated questionnaires
3. Methods The investigators propose a multi-centre phase II randomized-controlled trial of 138 patients deemed appropriate for focal therapy based on current standard-of-care (SOC) diagnostic work-up to be randomized to receive 18F-PSMA-1007 imaging or no further imaging. Patients found to have bilateral disease by PSMA PET will be ineligible for focal therapy and will proceed with SOC treatments (radical prostatectomy or radiation therapy). Men with unilateral disease on PSMA PET as well as all men receiving no further imaging will undergo hemigland ablation followed by PSMA PET, MRI, and combined targeted and systematic biopsy 12 months after ablation. The primary outcome will be the detection of Gleason Grade Group 2 or higher prostate cancer in men 12 months after hemigland ablation.

• Study Type: Interventional
• Enrollment (Estimated): 138
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Adam Kinnaird, MD, PhD; Phone Number: 321 (780) 407-5800; Email: ask@ualberta.ca
• Study Contact Backup: Name: Alexander Tamm, MD; Email: astamm@ualberta.ca

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Recruiting
      • University of Alberta Hospital
      • Contact: Alexander Tamm, MD; Phone Number: 780-407-6810; Email: astamm@ualberta.ca
    • Edmonton, Alberta, Canada, T5H 3V9
      • Recruiting
      • Royal Alexandra Hospital
      • Contact: Alexander Tamm, MD; Phone Number: 780-407-6810; Email: astamm@ualberta.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age > 50
2. Clinical stage < T2b
3. PSA < 15
4. Combined targeted and systematic MRI-guided biopsy shows unilateral Gleason Grade Group 2 or 3 prostate cancer

Exclusion Criteria:

1. Unable to obtain consent
2. Weight >250 kg (weight limitation of scanners)
3. Unable to lie flat for 30 minutes to complete the PET imaging
4. Lack of intravenous access
5. eGFR < 40 mL/min/1.73 m2 and/or a history of a severe reaction to CT contrast
6. Prior androgen deprivation therapy or radiation therapy to prostate gland

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PSMA PET; These patients will have been diagnosed with unilateral prostate cancer by standard of care diagnostic tests deemed eligible and interested in focal therapy. These patients will be randomized to undergo a single [18]F-PSMA-1007 PET/CT or PET/MRI scan prior to focal therapy. If they are diagnosed with bilateral disease, they will be ineligible for focal therapy and be referred for radical therapy. Those with unilateral disease will then proceed to focal therapy. They will then receive PSMA PET, MRI, and combined targeted and systematic biopsy 12 months after ablation Intravenous bolus injection of 4 MBq/kg +/- 10% of [18]F-PSMA-1007, up to a maximum of 400 MBq.	Diagnostic test: PSMA-1007 Positron Emission Tomography (PET) scan; Additional staging PET scan prior to focal therapy to focal therapy.
No Intervention: No Additional Imaging; These patients will have been diagnosed with unilateral prostate cancer by standard of care diagnostic tests deemed eligible and interested in focal therapy. These patients will undergo no further testing and will undergo focal therapy. They will then receive PSMA PET, MRI, and combined targeted and systematic biopsy 12 months after ablation. Intravenous bolus injection of 4 MBq/kg +/- 10% of [18]F-PSMA-1007, up to a maximum of 400 MBq.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Staging- Detection of any clinically significant prostate cancer	Detection of any clinically significant prostate cancer (defined as greater than or equal to Gleason Grade Group 2) at MRI-guided combined targeted and systematic biopsy	12 months after hemigland ablation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side Effects of Intervention	Number of patients with Side effects of PSMA PET imaging	Immediately after the imaging
Early Economic analysis	Comparison of the direct health care system costs incurred by each patient in both trials arms at the 1 year mark after hemigland ablation. Health system resource utilisation data will be captured using the administrative data infrastructures of the health care systems hosting the study centres, combined with data from the study clinical case report form. Unit costs for all resources will be obtained from CIHI and health system specific cost databases.	12 months after hemigland ablation
Post Trial Economic analysis	Comparison of the direct health care system costs incurred by each patient in both trials arms at the 5 year mark after hemigland ablation at the time of study completion. Health system resource utilisation data will be captured using the administrative data infrastructures of the health care systems hosting the study centres, combined with data from the study clinical case report form. Unit costs for all resources will be obtained from CIHI and health system specific cost databases.	Through Study Completion, completion by end of study at 5 year mark
Tumor Staging - bilateral disease on PSMA PET prior to hemi-gland ablation	The number of men found to have bilateral disease on PSMA PET prior to hemi-gland ablation	Prior to hemigland ablation - at study enrollment
Tumor Staging - bilateral disease on PSMA PET after hemi-gland ablation	The number of men found to have bilateral disease on PSMA PET after hemi-gland ablation	12 months after hemigland ablation.
Tumor Staging- rate of contralateral Gleason Grade Group 2 or greater prostate cancer at biopsy	The rate of contralateral Gleason Grade Group 2 or greater prostate cancer at time of biopsy	12 months after hemigland ablation.
Tumor Staging - rate of contralateral Gleason Grade Group 2 or greater prostate cancer at final pathology	The rate of contralateral Gleason Grade Group 2 or greater prostate cancer at final pathology in men undergoing radical prostatectomy after PSMA PET detected bilateral disease	Through study completion, expected within 1 year of randomization
Tumor Staging - 5-year failure free survival	5-year failure free survival defined as freedom from radical or systematic therapies, metastasis, prostate cancer specific and overall survivals.	5 years after hemigland ablation
Quality of Life Outcomes - EPIC-26	The EPIC-26 is a short form questionnaire designed to measure Quality of Life (QOL) issues in patients with prostate cancer. Response options for each EPIC item form a Likert scale, and multi-item scale scores are transformed linearly to a 0-100 scale with higher scores representing better Health Related QOL.	Through Study Completion, completion by end of study at 5 year mark. Every 3 months for first year and every 6months-1 year after
Quality of Life Outcomes - AUA Symptom Score	The AUA Symptom Score evaluates impact and severity of urinary symptoms in patients with benign prostatic hyperplasia (BPH). The AUA Symptom Score ranges from 0 to 35, with higher scores indicating more severe symptoms.	Through Study Completion, completion by end of study at 5 year mark. Every 3 months for first year and every 6months-1 year after
Quality of Life Outcomes - IIEF 5	The IIEF-5 is a short form version of a patient-reported outcome measure to evaluate erectile dysfunction and other sexual problems in men. THE IIEF-5 scale ranges from 5-25 with a higher score indicating less severe symptoms.	Through Study Completion, completion by end of study at 5 year mark. Every 3 months for first year and every 6months-1 year after
Quality of Life Outcomes - EQ-5D-5L	The EQ-5D-5L questionnaire is a self-assessed, health-related, quality of life questionnaire that measures quality of life on a 5-component scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The questionnaire can be used to derive a summary index score, which ranges from 0.000 (death) to 1.000 (perfect health).	Through Study Completion, completion by end of study at 5 year mark. Every 3 months for first year and every 6months-1 year after

Collaborators and Investigators

• Sponsor: University of Alberta

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2024
• Primary Completion (Estimated): February 26, 2029
• Study Completion (Estimated): February 26, 2029

Study Registration Dates

• First Submitted: August 7, 2023
• First Submitted That Met QC Criteria: August 14, 2023
• First Posted (Actual): August 22, 2023

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Prostate Cancer; Focal Therapy; Localized Prostate Cancer; PSMA Pet
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: HREBA.CC-23-0330

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No