Prostate Cancer
Conditions
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.
Interventions
DRUGGa-68 labeled HBED-CC PSMA
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.
DEVICEPositron Emission Tomography (PET) image combined with Computed Tomography (CT) (PET/CT)
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
DEVICEPositron Emission Tomography (PET) image combined with Magnetic Resonance Imaging (MRI) (PET/MRI)
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.
Sponsors
Thomas Hope
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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.).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited through clinicians located at San Francisco Veteran's Affairs Medical Center and University of California, San Francisco Helen Diller Family Comprehensive Cancer Center
Participants by arm
| Arm | Count |
|---|---|
| High-risk Prostate Cancer Pre-prostatectomy (preRP) Population 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. | 75 |
| Biochemical Recurrence (BCR) Population 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. | 150 |
| Castrate Resistant Prostate Cancer (CRCP) Population 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. | 0 |
| Total | 225 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Did not complete prostatectomy per protocol stipulation | 33 | 0 | 0 |
Baseline characteristics
| Characteristic | High-risk Prostate Cancer Pre-prostatectomy (preRP) Population | Biochemical Recurrence (BCR) Population | Total |
|---|---|---|---|
| Age, Customized 40-49 years old | 1 Participants | 1 Participants | 2 Participants |
| Age, Customized 50-59 years old | 15 Participants | 14 Participants | 29 Participants |
| Age, Customized 60-69 years old | 28 Participants | 60 Participants | 88 Participants |
| Age, Customized 70-79 years old | 29 Participants | 64 Participants | 93 Participants |
| Age, Customized 80-89 years old | 2 Participants | 10 Participants | 12 Participants |
| Age, Customized 90-99 years old | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 69 Participants | 4 Participants | 73 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 130 Participants | 132 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 16 Participants | 20 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 61 Participants | 0 Participants | 61 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 5 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 10 Participants | 18 Participants | 28 Participants |
| Race (NIH/OMB) White | 0 Participants | 125 Participants | 125 Participants |
| Region of Enrollment United States | 75 participants | 150 participants | 225 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 75 Participants | 150 Participants | 225 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 75 | 0 / 150 |
| other Total, other adverse events | 0 / 75 | 0 / 150 |
| serious Total, serious adverse events | 0 / 75 | 0 / 150 |
Outcome results
Primary
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.
Time frame: one month
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High-risk Prostate Cancer Pre-prostatectomy (preRP) Population | Negative Predictive Value (NPV) of Ga-68 HBED-CC PSMA for Detection of Nodal Metastasis | .74 proportion of true negatives |
| Biochemical Recurrence (BCR) Population | Negative Predictive Value (NPV) of Ga-68 HBED-CC PSMA for Detection of Nodal Metastasis | .24 proportion of true negatives |
Primary
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.
Time frame: 1 day
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High-risk Prostate Cancer Pre-prostatectomy (preRP) Population | Positive Predictive Value (PPV) of Ga-68 HBED-CC PSMA for Detection of Nodal Metastasis | .67 proportion of true positives |
| Biochemical Recurrence (BCR) Population | Positive Predictive Value (PPV) of Ga-68 HBED-CC PSMA for Detection of Nodal Metastasis | .906 proportion of true positives |
Primary
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.
Time frame: 1 day
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High-risk Prostate Cancer Pre-prostatectomy (preRP) Population | Sensitivity of Ga-68 HBED-CC PSMA for Detection of Nodal Metastases | .59 proportion of participants |
| Biochemical Recurrence (BCR) Population | Sensitivity of Ga-68 HBED-CC PSMA for Detection of Nodal Metastases | .89 proportion of participants |
Primary
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.
Time frame: 1 day
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High-risk Prostate Cancer Pre-prostatectomy (preRP) Population | Specificity of Ga-68 HBED-CC PSMA for Detection of Nodal Metastasis | .80 proportion of participants |
| Biochemical Recurrence (BCR) Population | Specificity of Ga-68 HBED-CC PSMA for Detection of Nodal Metastasis | .31 proportion of participants |
Secondary
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.
Time frame: Up to 1 year
Population: Surveys for only 126 BCR participants were completed by their physicians
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High-risk Prostate Cancer Pre-prostatectomy (preRP) Population | Number of Patients in Biochemical Recurrence (BCR) Group Who Had a Reported Change in Medical Management | Major Change | 67 Participants |
| High-risk Prostate Cancer Pre-prostatectomy (preRP) Population | Number of Patients in Biochemical Recurrence (BCR) Group Who Had a Reported Change in Medical Management | Minor Change | 8 Participants |
Secondary
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)).
Time frame: Up to 1 year
Population: Six patients did not have an evaluable PSA value pre-imaging for this analysis
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High-risk Prostate Cancer Pre-prostatectomy (preRP) Population | Overall Detection Rates of Ga68-PSMA-11 by PSA Levels for the BCR Group | <0.5 ng/dl | .55 proportion of participants |
| High-risk Prostate Cancer Pre-prostatectomy (preRP) Population | Overall Detection Rates of Ga68-PSMA-11 by PSA Levels for the BCR Group | 0.5 to < 1.0 ng/dl | .62 proportion of participants |
| High-risk Prostate Cancer Pre-prostatectomy (preRP) Population | Overall Detection Rates of Ga68-PSMA-11 by PSA Levels for the BCR Group | 1.0 to < 2.0 ng/dl | .80 proportion of participants |
| High-risk Prostate Cancer Pre-prostatectomy (preRP) Population | Overall Detection Rates of Ga68-PSMA-11 by PSA Levels for the BCR Group | 2.0 to < 5.0 ng/dl | .88 proportion of participants |
| High-risk Prostate Cancer Pre-prostatectomy (preRP) Population | Overall Detection Rates of Ga68-PSMA-11 by PSA Levels for the BCR Group | >=5.0 ng/dl | .96 proportion of participants |