Prostate Cancer
Conditions
Brief summary
The investigators are imaging patients with prostate cancer using a new PET imaging agent (Ga-68-PSMA-11) in order to evaluate it's ability to detection prostate cancer in patients with biochemical recurrence after prostatectomy and radiation therapy.
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 PSMA-11 in order to demonstrate its utility. The investigators plan to utilize this data to obtain further approvals of the Ga-68-PSMA-11 compound, so that this agent will become available for clinical imaging in prostate cancer patients. In the biochemical recurrence population, the primary objective is to determine the sensitivity and positive predictive value (PPV) on a per-patient and per-region-basis of 68Ga-PSMA-11 PET for detection of tumor location confirmed by histopathology/biopsy.
Interventions
Patients will be imaged using Ga-68 labeled PSMA-11 PET to determine if the presence of metastatic disease. Prostate Specific Membrane Antigen (PSMA) is a protein expressed on prostate cancer cells that can be imaged using small molecules that target this protocol.
Sponsors
University of California, San Francisco
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histopathological proven prostate adenocarcinoma. * Rising prostate-specific antigen (PSA) after definitive therapy with prostatectomy or radiation therapy (external beam or brachytherapy). * Post radical prostatectomy (RP) - American Urological Association (AUA) recommendation * PSA greater than 0.2 ng/mL measured more than 6 weeks after RP and, * Confirmatory persistent PSA greater than 0.2 ng/mL * Post-radiation therapy -ASTRO-Phoenix consensus definition * Nadir + greater than or equal to 2 ng/mL rise in PSA * Karnofsky performance status of greater than 50 (or Eastern Cooperative Oncology Group (ECOG) /World Health Organization (WHO) equivalent). * Age \> 18. * Ability to understand a written informed consent document, and the willingness to sign it.
Exclusion criteria
* Investigational therapy for prostate cancer. * Unable to lie flat, still or tolerate a PET scan. * Prior history of any other malignancy within the last 2 years, other than skin basal cell or cutaneous superficial squamous cell carcinoma that has not metastasized and superficial bladder cancer. * Contraindication to furosemide administration including prior allergy or adverse reaction to furosemide or sulfa drugs. (Note: This
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Positive Predictive Value (PPV) on a Per-patient Basis With Histologic Validation | 1 month | PPVs were calculated across the group on a per-patient basis on 68Ga-PSMA-11 PET for detection of tumor location confirmed by histopathology/biopsy and reported along with the corresponding two-sided 95% confidence intervals (CI). The CIs were constructed using the Wilson score method. |
| Positive Predictive Value (PPV) on a Per-region Basis With Histologic Validation | 1 month | PPVs were calculated across the group on a per-region-basis on 68Ga-PSMA-11 PET for detection of tumor location confirmed by histopathology/biopsy and reported along with the corresponding two-sided 95% CIs. The CIs were constructed using the Wilson score method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity on a Per-patient Basis | 1 month | Sensitivity, on a per-patient basis of 68Ga-PSMA-11 PET for detection of tumor location confirmed by histopathology/biopsy was calculated. The 95% CI was calculated using the Wilson score method. |
| Sensitivity on a Per-region Basis | 1 month | Sensitivity, on a per-region basis of 68Ga-PSMA-11 PET for detection of tumor location confirmed by histopathology/biopsy was calculated. The 95% CI was calculated using the Wilson score method. |
| Detection Rates of 68Ga-PSMA-11 PET Stratified by Prostate-specific Antigen (PSA) Value | 1 month | Detection rate was defined as proportion of 68Ga-PSMA-11 PET positive patients, independent of the reference standard stratified by PSA value (0.2-\<0.5; 0.5-\<1.0; 1.0-\<2.0; 2.0-\<5.0, and ≥5.0). |
| PPVs on a Per-patient of 68Ga-PSMA-11 PET With Conventional Imaging Follow-up | 1 month | PPVs on a per-patient basis of 68Ga-PSMA-11 PET for detection of tumor location confirmed by conventional imaging follow-up were calculated and reported along with the corresponding two-sided 95% CI. |
| Percentage of Participants With Change in Clinical Management | Up to 1 year | Clinical management changes were assessed using surveys of Intended Management to determine the percent change in clinical management after 68Ga-PSMA-11 PET. |
| Safety Assessment - Heart Rate | 1 day | Patient vital signs were measured before and after 68Ga-PSMA-11 injections and absolute mean change was calculated. |
| Safety Assessment - Blood Pressure | 1 day | Patient vital signs were measured before and after 68Ga-PSMA-11 injections and absolute mean change was calculated. |
| Inter-reader Agreement Per-region | 1 month | Inter-reader reproducibility for positivity at region level was reported using the Fleiss' Kappa test for multiple readers. Kappa value varies from 0 (no agreement) to 1 (perfect agreement). |
| PPVs on a Per-region of 68Ga-PSMA-11 PET With Conventional Imaging Follow-up | 1 month | PPVs on a per-region-basis of 68Ga-PSMA-11 PET for detection of tumor location confirmed by histopathology/biopsy and conventional imaging follow-up were calculated and reported along with the corresponding two-sided 95% CI. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ga-68 Labeled PSMA-11 PET PSMA PET imaging: Patients will receive Ga-68 labeled PSMA-11 PET and then undergo PET/CT or PET/MRI approximately 55-70 minutes later.
Ga-68 labeled PSMA-11 PET: Patients will be imaged using Ga-68 labeled PSMA-11 PET to determine if the presence of metastatic disease. Prostate Specific Membrane Antigen (PSMA) is a protein expressed on prostate cancer cells that can be imaged using small molecules that target this protocol. | 385 |
| Total | 385 |
Baseline characteristics
| Characteristic | Ga-68 Labeled PSMA-11 PET |
|---|---|
| Age, Customized Age | 70 years |
| Initial therapy Prostatectomy and Salvage Radiotherapy | 129 Participants |
| Initial therapy Prostatectomy only | 132 Participants |
| Initial therapy Radiotherapy only | 124 Participants |
| Race/Ethnicity, Customized Asian | 15 Participants |
| Race/Ethnicity, Customized Black or African American | 8 Participants |
| Race/Ethnicity, Customized Native American and Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian | 0 Participants |
| Race/Ethnicity, Customized Other | 14 Participants |
| Race/Ethnicity, Customized Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Unknown | 29 Participants |
| Race/Ethnicity, Customized White | 318 Participants |
| Region of Enrollment United States | 385 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 385 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 385 |
| other Total, other adverse events | 0 / 385 |
| serious Total, serious adverse events | 0 / 385 |
Outcome results
Primary
Positive Predictive Value (PPV) on a Per-patient Basis With Histologic Validation
PPVs were calculated across the group on a per-patient basis on 68Ga-PSMA-11 PET for detection of tumor location confirmed by histopathology/biopsy and reported along with the corresponding two-sided 95% confidence intervals (CI). The CIs were constructed using the Wilson score method.
Time frame: 1 month
Population: All subjects who received a 68Ga-PSMA-11 injection, had their 68Ga-PSMA-11 scan independently and blindly interpreted on a per patient basis. Per patient analyses included an evaluation of positive or negative for presence of localized prostate cancer (PCa).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pet Positive (Per Patient) | Positive Predictive Value (PPV) on a Per-patient Basis With Histologic Validation | 0.90 percentage of times value is true |
Primary
Positive Predictive Value (PPV) on a Per-region Basis With Histologic Validation
PPVs were calculated across the group on a per-region-basis on 68Ga-PSMA-11 PET for detection of tumor location confirmed by histopathology/biopsy and reported along with the corresponding two-sided 95% CIs. The CIs were constructed using the Wilson score method.
Time frame: 1 month
Population: All subjects who received a 68Ga-PSMA-11 injection, had their 68Ga-PSMA-11 scan independently and blindly interpreted on a per region basis. Per region analyses included an evaluation of positive or negative for presence of PCa. Regional analyses included prostate bed, pelvic nodes, extrapelvic non-bone, and bone.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pet Positive (Per Patient) | Positive Predictive Value (PPV) on a Per-region Basis With Histologic Validation | 0.91 percentage of times value is true |
Secondary
Detection Rates of 68Ga-PSMA-11 PET Stratified by Prostate-specific Antigen (PSA) Value
Detection rate was defined as proportion of 68Ga-PSMA-11 PET positive patients, independent of the reference standard stratified by PSA value (0.2-\<0.5; 0.5-\<1.0; 1.0-\<2.0; 2.0-\<5.0, and ≥5.0).
Time frame: 1 month
Population: Portion of patients with 68Ga-PSMA-11 PET positive findings were stratified by PSA range and disease location in accordance with Prostate Magnetic Resonance Imaging Study (PROMIS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pet Positive (Per Patient) | Detection Rates of 68Ga-PSMA-11 PET Stratified by Prostate-specific Antigen (PSA) Value | 40 percentage detected |
| PSA 0.5 - <1.0 | Detection Rates of 68Ga-PSMA-11 PET Stratified by Prostate-specific Antigen (PSA) Value | 51 percentage detected |
| PSA 1.0 - <2.0 | Detection Rates of 68Ga-PSMA-11 PET Stratified by Prostate-specific Antigen (PSA) Value | 87 percentage detected |
| PSA 2.0 - <5.0 | Detection Rates of 68Ga-PSMA-11 PET Stratified by Prostate-specific Antigen (PSA) Value | 83 percentage detected |
| PSA ≥5.0 | Detection Rates of 68Ga-PSMA-11 PET Stratified by Prostate-specific Antigen (PSA) Value | 96 percentage detected |
Secondary
Inter-reader Agreement Per-region
Inter-reader reproducibility for positivity at region level was reported using the Fleiss' Kappa test for multiple readers. Kappa value varies from 0 (no agreement) to 1 (perfect agreement).
Time frame: 1 month
Population: Patients included in the analyses were scanned to include all regions under review
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pet Positive (Per Patient) | Inter-reader Agreement Per-region | 0.65 kappa |
| PSA 0.5 - <1.0 | Inter-reader Agreement Per-region | 0.73 kappa |
| PSA 1.0 - <2.0 | Inter-reader Agreement Per-region | 0.70 kappa |
| PSA 2.0 - <5.0 | Inter-reader Agreement Per-region | 0.78 kappa |
Secondary
Percentage of Participants With Change in Clinical Management
Clinical management changes were assessed using surveys of Intended Management to determine the percent change in clinical management after 68Ga-PSMA-11 PET.
Time frame: Up to 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pet Positive (Per Patient) | Percentage of Participants With Change in Clinical Management | 72 Percentage of participants |
Secondary
PPVs on a Per-patient of 68Ga-PSMA-11 PET With Conventional Imaging Follow-up
PPVs on a per-patient basis of 68Ga-PSMA-11 PET for detection of tumor location confirmed by conventional imaging follow-up were calculated and reported along with the corresponding two-sided 95% CI.
Time frame: 1 month
Population: One hundred and twenty-five patients had confirmed imaging at follow-up for this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pet Positive (Per Patient) | PPVs on a Per-patient of 68Ga-PSMA-11 PET With Conventional Imaging Follow-up | 0.81 percentage of times value is true |
Secondary
PPVs on a Per-region of 68Ga-PSMA-11 PET With Conventional Imaging Follow-up
PPVs on a per-region-basis of 68Ga-PSMA-11 PET for detection of tumor location confirmed by histopathology/biopsy and conventional imaging follow-up were calculated and reported along with the corresponding two-sided 95% CI.
Time frame: 1 month
Population: Two-hundred and forty-nine patients had confirmed regional imaging in follow up for this sample.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pet Positive (Per Patient) | PPVs on a Per-region of 68Ga-PSMA-11 PET With Conventional Imaging Follow-up | 0.92 percentage of times value is true |
Secondary
Safety Assessment - Blood Pressure
Patient vital signs were measured before and after 68Ga-PSMA-11 injections and absolute mean change was calculated.
Time frame: 1 day
Population: Pressure exerted by a 1 millimeter vertical column of mercury (Hg) at 0 degree Celsius is defined as (mmHg)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pet Positive (Per Patient) | Safety Assessment - Blood Pressure | Systolic blood pressure | 137.8 mmHg | Standard Deviation 17.7 |
| Pet Positive (Per Patient) | Safety Assessment - Blood Pressure | Diastolic blood pressure | 80.3 mmHg | Standard Deviation 33.8 |
| PSA 0.5 - <1.0 | Safety Assessment - Blood Pressure | Diastolic blood pressure | 81.1 mmHg | Standard Deviation 10.6 |
| PSA 0.5 - <1.0 | Safety Assessment - Blood Pressure | Systolic blood pressure | 137.0 mmHg | Standard Deviation 17.4 |
| PSA 1.0 - <2.0 | Safety Assessment - Blood Pressure | Diastolic blood pressure | 0.6 mmHg | Standard Deviation 34 |
| PSA 1.0 - <2.0 | Safety Assessment - Blood Pressure | Systolic blood pressure | 1.0 mmHg | Standard Deviation 18.6 |
Secondary
Safety Assessment - Heart Rate
Patient vital signs were measured before and after 68Ga-PSMA-11 injections and absolute mean change was calculated.
Time frame: 1 day
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pet Positive (Per Patient) | Safety Assessment - Heart Rate | 67.8 beats per minute | Standard Deviation 13.3 |
| PSA 0.5 - <1.0 | Safety Assessment - Heart Rate | 66.9 beats per minute | Standard Deviation 13.6 |
| PSA 1.0 - <2.0 | Safety Assessment - Heart Rate | 0.9 beats per minute | Standard Deviation 11.2 |
Secondary
Sensitivity on a Per-patient Basis
Sensitivity, on a per-patient basis of 68Ga-PSMA-11 PET for detection of tumor location confirmed by histopathology/biopsy was calculated. The 95% CI was calculated using the Wilson score method.
Time frame: 1 month
Population: Seventy-nine patients had confirmed patient histopathology validation for this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pet Positive (Per Patient) | Sensitivity on a Per-patient Basis | 0.92 percentage of sensitivity |
Secondary
Sensitivity on a Per-region Basis
Sensitivity, on a per-region basis of 68Ga-PSMA-11 PET for detection of tumor location confirmed by histopathology/biopsy was calculated. The 95% CI was calculated using the Wilson score method.
Time frame: 1 month
Population: Eighty-four patients had confirmed histopathology region validation for this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pet Positive (Per Patient) | Sensitivity on a Per-region Basis | 0.90 percentage of sensitivity |