Evaluation of Gallium-68-HBED-CC-PSMA Imaging in Prostate Cancer Patients

Study Overview
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Brief Summary
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The investigators are imaging patients with prostate cancer using a new PET imaging agent (Ga-68 HBED-CC PSMA) in order to evaluate it's ability to detection prostate cancer in patients with high risk disease prior to prostatectomy, patients with biochemical recurrence and patients with castrate resistant prostate cancer.

Detailed Description
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Imaging and staging of prostate cancer is critical for surgical and treatment planning. Patients with suspected metastatic prostate cancer will be imaged using Gallium-68 labeled HBED-CC PSMA in order to demonstrate its utility. The investigators plan to utilize this data to obtain further approvals of the HBED-CC PSMA compound, so that this agent will become available for clinical imaging in prostate cancer patients. This compound has been shown to be superior to choline based PET agents for the staging of prostate cancer, both Carbon-11 and Fluorine-18 compounds. But this compound was not patented and therefore no company or private entity will make the investment required to bring HBED-CC PSMA to market. In the vacuum of availability, academic groups must take the lead in order to collect the necessary data for future FDA approval. This study focuses on three patients populations that are imaged. In the pre-prostatectomy population, the primary objective is to determine the sensitivity and specificity for detection on nodal metastasis. In the biochemical recurrence population, the primary objective is to determine the sensitivity of recurrence location. In the castrate resistant prostate cancer population the primary objective is to determine if PSMA PET detects more metastatic lesions than conventional imaging.

Official Title
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Evaluation of Gallium-68 HBED-CC-PSMA Imaging in Prostate Cancer Patients

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Ga-68 labeled HBED-CC PSMA
* Device: Positron Emission Tomography (PET) image combined with Computed Tomography (CT) (PET/CT)
* Device: Positron Emission Tomography (PET) image combined with Magnetic Resonance Imaging (MRI) (PET/MRI)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Known prostate cancer with a clinical concern for the presence of metastatic disease as delineated below: Treatment naïve patients with one of the following risk factors: CAPRA (Cancer of the Prostate Risk Assessment) score ≥ 5, Prostate-specific antigen (PSA) ≥ 15 ng/mL and/or Gleason score ≥ 4+4. Patients with biochemical recurrence after prostatectomy or radiation therapy with a PSA doubling time less than 12 months. i. These patients may have received androgen deprivation therapy prior to imaging. Patients with castrate resistant prostate cancer with progressive disease as defined by Prostate Cancer Clinical Trials Working Group (PCWG2) criteria (27). i. Patients with castrate resistant prostate cancer can be either on treatment or off treatment Age > 18. Karnofsky performance status of > 50 (or Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) equivalent). Ability to understand a written informed consent document, and the willingness to sign it. Exclusion Criteria: Patients exceeding the weight limitations of the scanner or are not able to enter the bore of the PET scanner due to BMI. Inability to lie still for the entire imaging time (e.g. cough, severe arthritis, etc.). Inability to complete the needed investigational due to other reasons (severe claustrophobia, radiation phobia, etc.).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High-risk prostate cancer pre-prostatectomy (preRP) population<br>Patients with high-risk prostate cancer pre-prostatectomy. Patients receive Ga-68-HBED-CC-PSMA and then undergo PET/CT or PET/MRI approximately 55-70 minutes later. | Drug: Ga-68 labeled HBED-CC PSMA<br>* The imaging agent (Ga-68 HBED-CC PSMA) will be administered on an outpatient basis. It will be administered a single time intravenously prior to the PET/CT imaging. The one-time nominal injected dose will be 3 to 7 millicurie (mCi) containing 10 - 25 μg Ga-68 HBED-CC PSMA.<br>* Other names: Ga-68 labeled Glu-urea-Lys(Ahx)-HBED-CC;Device: Positron Emission Tomography (PET) image combined with Computed Tomography (CT) (PET/CT)<br>* Patient shall begin imaging between 55 and 70 minutes after the injection of the radiopharmaceutical. A PET/CT scan includes two parts: a PET scan and a CT scan. The CT portion of the scan produces a 3-D image that shows a patient's anatomy. The PET scan demonstrates function and what's occurring on a cellular level. The PET scan is unique because it images the radiation emitted from the patient while the CT records anatomical x-rays, showing the same area from another perspective<br>* Other names: PET/CT;Device: Positron Emission Tomography (PET) image combined with Magnetic Resonance Imaging (MRI) (PET/MRI)<br>* Patient shall begin imaging between 55 and 70 minutes after the injection of the radiopharmaceutical. A PET/MRI scan is a two-in-one test that combines images from a positron emission tomography (PET) scan and a magnetic resonance imaging (MRI) scan. Coverage for the scan will extend from the patients vertex through the mid thighs. We will use 4 minute acquisitions per bed position for PET imaging.<br>* Other names: PET/MRI;|
| Experimental: Biochemical Recurrence (BCR)<br>Patients with prostate cancer with biochemical recurrence Patients receive Ga-68-HBED-CC-PSMA and then undergo PET/CT or PET/MRI approximately 55-70 minutes later. | Drug: Ga-68 labeled HBED-CC PSMA<br>* The imaging agent (Ga-68 HBED-CC PSMA) will be administered on an outpatient basis. It will be administered a single time intravenously prior to the PET/CT imaging. The one-time nominal injected dose will be 3 to 7 millicurie (mCi) containing 10 - 25 μg Ga-68 HBED-CC PSMA.<br>* Other names: Ga-68 labeled Glu-urea-Lys(Ahx)-HBED-CC;Device: Positron Emission Tomography (PET) image combined with Computed Tomography (CT) (PET/CT)<br>* Patient shall begin imaging between 55 and 70 minutes after the injection of the radiopharmaceutical. A PET/CT scan includes two parts: a PET scan and a CT scan. The CT portion of the scan produces a 3-D image that shows a patient's anatomy. The PET scan demonstrates function and what's occurring on a cellular level. The PET scan is unique because it images the radiation emitted from the patient while the CT records anatomical x-rays, showing the same area from another perspective<br>* Other names: PET/CT;Device: Positron Emission Tomography (PET) image combined with Magnetic Resonance Imaging (MRI) (PET/MRI)<br>* Patient shall begin imaging between 55 and 70 minutes after the injection of the radiopharmaceutical. A PET/MRI scan is a two-in-one test that combines images from a positron emission tomography (PET) scan and a magnetic resonance imaging (MRI) scan. Coverage for the scan will extend from the patients vertex through the mid thighs. We will use 4 minute acquisitions per bed position for PET imaging.<br>* Other names: PET/MRI;|
| Experimental: Castrate Resistant Prostate cancer (CRCP) population<br>Patients with castrate resistant prostate cancer. Patients receive Ga-68-HBED-CC-PSMA and then undergo PET/CT or PET/MRI approximately 55-70 minutes later. | Drug: Ga-68 labeled HBED-CC PSMA<br>* The imaging agent (Ga-68 HBED-CC PSMA) will be administered on an outpatient basis. It will be administered a single time intravenously prior to the PET/CT imaging. The one-time nominal injected dose will be 3 to 7 millicurie (mCi) containing 10 - 25 μg Ga-68 HBED-CC PSMA.<br>* Other names: Ga-68 labeled Glu-urea-Lys(Ahx)-HBED-CC;Device: Positron Emission Tomography (PET) image combined with Computed Tomography (CT) (PET/CT)<br>* Patient shall begin imaging between 55 and 70 minutes after the injection of the radiopharmaceutical. A PET/CT scan includes two parts: a PET scan and a CT scan. The CT portion of the scan produces a 3-D image that shows a patient's anatomy. The PET scan demonstrates function and what's occurring on a cellular level. The PET scan is unique because it images the radiation emitted from the patient while the CT records anatomical x-rays, showing the same area from another perspective<br>* Other names: PET/CT;Device: Positron Emission Tomography (PET) image combined with Magnetic Resonance Imaging (MRI) (PET/MRI)<br>* Patient shall begin imaging between 55 and 70 minutes after the injection of the radiopharmaceutical. A PET/MRI scan is a two-in-one test that combines images from a positron emission tomography (PET) scan and a magnetic resonance imaging (MRI) scan. Coverage for the scan will extend from the patients vertex through the mid thighs. We will use 4 minute acquisitions per bed position for PET imaging.<br>* Other names: PET/MRI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of Ga-68 HBED-CC PSMA for Detection of Nodal Metastases | Patients who have a positive node on imaging and on pathology will be considered a true-positive. Patients who have no nodes on imaging and pathology will be considered true- negatives. Patients with positive nodes on imaging and negative on pathology will be considered false positives and those with positive nodes on pathology but negative on imaging will be considered false negatives. Point estimate of the true positive rate will be calculated with the corresponding 95% confidence interval. | 1 day | 
| Specificity of Ga-68 HBED-CC PSMA for Detection of Nodal Metastasis | Patients who have a positive node on imaging and on pathology will be considered a true-positive. Patients who have no nodes on imaging and pathology will be considered true- negatives. Patients with positive nodes on imaging and negative on pathology will be considered false positives and those with positive nodes on pathology but negative on imaging will be considered false negatives. Point estimate of the true negative rate will be calculated with the corresponding 95% confidence interval. | 1 day | 
| Positive Predictive Value (PPV) of Ga-68 HBED-CC PSMA for Detection of Nodal Metastasis | Patients who have a positive node on imaging and on pathology will be considered a true-positive. Patients who have no nodes on imaging and pathology will be considered true- negatives. Patients with positive nodes on imaging and negative on pathology will be considered false positives and those with positive nodes on pathology but negative on imaging will be considered false negatives. Point estimate of the true negative rate will be calculated with the corresponding 95% confidence interval. | 1 day | 
| Negative Predictive Value (NPV) of Ga-68 HBED-CC PSMA for Detection of Nodal Metastasis | Patients who have a positive node on imaging and on pathology will be considered a true-positive. Patients who have no nodes on imaging and pathology will be considered true- negatives. Patients with positive nodes on imaging and negative on pathology will be considered false positives and those with positive nodes on pathology but negative on imaging will be considered false negatives. Point estimate of the true negative rate will be calculated with the corresponding 95% confidence interval. | one month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Detection Rates of Ga68-PSMA-11 by PSA Levels for the BCR Group | 68Ga-labeled prostate-specific membrane antigen 11 (Ga68-PSMA-11) PET positivity rate by prostate-specific antigen (PSA) level is calculated by the number of positive reads divided by the total number of patients in the BCR Group per PSA value quintile (Detection rate (d) = total number of positive reads (t)/ total number of participants (N)). | Up to 1 year | 
| Number of Patients in Biochemical Recurrence (BCR) Group Who Had a Reported Change in Medical Management | Change in participant medical management was determined based on the results of surveys given to each participant's treating physician. Results of the survey were categorized as a major change in participant's medical management, a minor change in participant's medical management, no change to participant's medical management, or change to participant's medical management is unknown. These categories were developed based on a predetermined categorization schema. | Up to 1 year |