PSMA-PET for Biopsy and Treatment Guidance in Primary Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
The overall objective of this Early Phase Clinical Trial is to begin defining the accuracy of 68Ga-PSMA-11 for detecting the location and size of clinically significant prostate cancer lesions in low and intermediate risk disease. A molecularly-targeted probe (68Ga-PSMA-11), coupled with an advanced clinical imaging system (Siemens Biograph VisionPET-CT), will improve accuracy during biopsy and staging. We propose detailed intra-lesion whole-mount pathologic analysis as the gold standard for critically assessing PSMA PET accuracy in patients undergoing surgery, and blinded PSMA PET-CT comparison with standard multi-parametric MRI (mpMRI) for patients having biopsy on active surveillance. This intensive testing of the accuracy and value of PSMA-based tracers requires our unique collaboration of surgeons, radiologists, pathologists, and imaging scientists with decades of experience and innovation.

Detailed Description
-----------------
This is a prospective, single arm, phase 2 clinical trial. This patient population will have low (1 = Gleason 3 + 3) or intermediate risk (2 = 3 + 4; 3 = 4 + 3) prostate cancer. It will also enroll those who are at high risk of significant prostate cancer (4Kscore >20%, SelectMDx >20%, PSA density >0.15). Patients will be scheduled for magnetic resonance imaging (MRI) as part of routine care for either surgical planning or for further biopsy. Following the informed consent process, patients who enroll in the study will receive a PSMA positron emission tomography (PET) study along with their standard of care (SOC) MRI on an integrated PET-MRI. Registration of PET and MRI will be done using software to generate the PET-MRI images. Patients receiving SOC MRI guided biopsy will receive additional PET guided biopsies as indicated in a single session. The sensitivity and specificity will be evaluated along with the ability of the tracer to inform the treatment planning. Patients receiving surgical removal of the prostate will have a slice-by-slice whole mount analysis to assess the sensitivity and specificity the PSMA PET. Primary Objectives Define the accuracy of 68Ga-PSMA-11 PET-CT for detecting the clinically significant prostate cancer lesion. Secondary Objectives Evaluate how knowledge of the PSMA-PET might inform treatment planning. Exploratory Objectives Generate pilot data for future larger clinical trials

Official Title
-----------------
PSMA-PET for Biopsy and Treatment Guidance in Primary Prostate Cancer

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Diagnostic Test: 68Ga-PSMA-11 PET-MRI


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ≥ 18 years of age Must provide written informed consent Presence of low or intermediate risk prostate cancer or at risk of having intermediate risk cancer a. Intermediate risk prostate cancer: i. Grade group 2 = 3 + 4, or ii. Grade group 3 = 4 + 3 b. At Risk of intermediate risk prostate cancer: i. 4K score ≥ 20%, or ii. Select MDx ≥ 20%, or iii. PSA Density ≥ 0.15 iv. Grade group 1= 3+3 (iv. Note: Where multiple cancer lesions are present on biopsy, it is allowable to have Gleason 8 or 9 cancer lesions if they are in addition to the intermediate risk cancer as described above.) Scheduled for MRI or has recently completed SOC MRI (within 6 months) for further biopsy, or surgical removal, or focal therapy. Willing and able to lie still for approximately 50 minutes in an enclosed space for the CT. Exclusion Criteria: Participation in another investigational trial involving research exposure to ionizing radiation concurrently or within 30 days. Does not meet safety criteria for MRI scan (e.g. metal implant that is not allowed). Significant acute or chronic medical, neurologic, or psychiatric illness in the subject that, in the judgment of the Principal Investigator, could compromise subject safety, limit the subject's ability to complete the study, and/or compromise the objectives of the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: 68Ga-PSMA-11 PET will be performed and we will study how the knowledge of the results helps inform treatment decisions.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prostate cancer- men being treated with radical prostatectomy<br>Men being treated for prostate cancer with radical prostatectromy were enrolled in this arm. | Diagnostic Test: 68Ga-PSMA-11 PET-MRI<br>* Patients will undergo injection of 68Ga-PSMA-11 at the time of pre-treatment MRI scan and followed until biopsy and/or surgical resection.<br>|
| Experimental: Prostate cancer- men undergoing cancer screening or active surveillance<br>Men undergoing cancer screening or active surveillance were enrolled in this arm. | Diagnostic Test: 68Ga-PSMA-11 PET-MRI<br>* Patients will undergo injection of 68Ga-PSMA-11 at the time of pre-treatment MRI scan and followed until biopsy and/or surgical resection.<br>|
| Experimental: Prostate cancer- focal therapy<br>Men undergoing focal therapy with high intensity focused ultrasound are in this group. | Diagnostic Test: 68Ga-PSMA-11 PET-MRI<br>* Patients will undergo injection of 68Ga-PSMA-11 at the time of pre-treatment MRI scan and followed until biopsy and/or surgical resection.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic Accuracy of PSMA PET | Sensitivity and specificity for EPE using whole-mount analysis or biopsy pathology. EPE is extra-prostatic extension which means the cancer extends beyond the boundary of the prostate into adjacent muscle or fatty tissue. | 60 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of PSMA PET-CT on Treatment Plan for Surgery or Biopsy | Does the PSMA-PET change the treatment or biopsy decision. The surgeon will look at imaging prior to a procedure (prostatectomy, HIFU, or biopsy) to see if it informs the procedure steps. Does the imaging add new information about the cancer that could alter the biopsy or treatment? PSMA-PET scans were obtained in 3 different contexts as listed below (prior to prostate removal, screening for cancer or on active surveillance, and prior to focal therapy). We calculate the percentage of cases that had the treatment or followup plan altered by the investigational imaging agent. For example, if the PET imaging showed cancer was organ confined, then the surgeon may elect to increase the nerve sparing. For the active surveillance group, if this PET imaging showed a new lesion in the prostate, when compared to ultrasound or MRI, then the biopsy may have been altered to target this new lesion. For focal therapy, the treatment could be expanded to ensure any new PET lesions are covered. | 60 days |