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

Phase 2

Completed

• Conditions: Prostate Cancer
• Interventions: 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)

• Registration Number: NCT02611882
• Lead Sponsor: Thomas Hope

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2015-09-29
• Study First Submitted QC: 2015-11-19
• Study First Posted: 2015-11-23
• Study Start: 2015-12-18
• Primary Completion: 2016-10-24
• Study Completion: 2016-10-24
• Disposition First Submitted: 2018-04-06
• Disposition First Submitted QC: 2018-04-06
• Disposition First Posted: 2018-04-10
• Status Verified: 2020-11
• Results First Submitted: 2020-11-03
• Results First Submitted QC: 2020-11-26
• Last Update Submitted: 2020-11-26
• Results First Posted: 2020-12-22
• Last Update Posted: 2020-12-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 225

Inclusion Criteria

1. 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

2. Age > 18.

3. Karnofsky performance status of > 50 (or Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) equivalent).

4. Ability to understand a written informed consent document, and the willingness to sign it.

Exclusion Criteria

1. Patients exceeding the weight limitations of the scanner or are not able to enter the bore of the PET scanner due to BMI.
2. Inability to lie still for the entire imaging time (e.g. cough, severe arthritis, etc.).
3. Inability to complete the needed investigational due to other reasons (severe claustrophobia, radiation phobia, etc.).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Biochemical Recurrence (BCR)	Positron Emission Tomography (PET) image combined with Magnetic Resonance Imaging (MRI) (PET/MRI)	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.
Castrate Resistant Prostate cancer (CRCP) population	Ga-68 labeled HBED-CC PSMA	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.
Biochemical Recurrence (BCR)	Positron Emission Tomography (PET) image combined with Computed Tomography (CT) (PET/CT)	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.
High-risk prostate cancer pre-prostatectomy (preRP) population	Positron Emission Tomography (PET) image combined with Magnetic Resonance Imaging (MRI) (PET/MRI)	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.
High-risk prostate cancer pre-prostatectomy (preRP) population	Ga-68 labeled HBED-CC PSMA	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.
High-risk prostate cancer pre-prostatectomy (preRP) population	Positron Emission Tomography (PET) image combined with Computed Tomography (CT) (PET/CT)	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.
Biochemical Recurrence (BCR)	Ga-68 labeled HBED-CC PSMA	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.
Castrate Resistant Prostate cancer (CRCP) population	Positron Emission Tomography (PET) image combined with Computed Tomography (CT) (PET/CT)	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.
Castrate Resistant Prostate cancer (CRCP) population	Positron Emission Tomography (PET) image combined with Magnetic Resonance Imaging (MRI) (PET/MRI)	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.

Primary Outcome Measures

Name	Time	Method
Specificity of Ga-68 HBED-CC PSMA for Detection of Nodal Metastasis	1 day	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.
Sensitivity of Ga-68 HBED-CC PSMA for Detection of Nodal Metastases	1 day	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.
Positive Predictive Value (PPV) of Ga-68 HBED-CC PSMA for Detection of Nodal Metastasis	1 day	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.
Negative Predictive Value (NPV) of Ga-68 HBED-CC PSMA for Detection of Nodal Metastasis	one month	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.

Secondary Outcome Measures

Name	Time	Method
Overall Detection Rates of Ga68-PSMA-11 by PSA Levels for the BCR Group	Up to 1 year	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)).
Number of Patients in Biochemical Recurrence (BCR) Group Who Had a Reported Change in Medical Management	Up to 1 year	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.

Trial Locations

Locations (1)

University of California, San Francisco; 🇺🇸 San Francisco, California, United States