Prostate Cancer, Prostate Adenocarcinoma, Prostate Cancer Metastatic, Prostate Cancer Recurrent
Conditions
Brief summary
This study evaluates the value of Gallium-68 labeled PSMA (68Ga-PSMA) for PET/CT imaging of prostate cancer recurrence. 68Ga-PSMA is a radioactive molecule, which binds to prostate cancer cells. Together with a PET/CT scanner, the distribution of 68Ga-PSMA can be determined in the body. To test this new drug, participants will receive an intravenous injection of Ga-68-PSMA and then have a PET/CT scan. The scan results will be made available to study participants and treating physicians.
Detailed description
This study evaluates Gallium-68 labelled PSMA-11 (also called Gallium-68 labelled PSMA-HBED-CC, or Gallium-68 labelled PSMA N,N'-bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid), abbreviated here as 68Ga-PSMA. This molecule (or radiotracer) binds to receptors that are often present on prostate cancer cells. Using 68Ga-PSMA together with a positron emission tomography (PET) scanner (with computed tomography, called PET/CT), it is therefore possible to find prostate cancer lesions in the body. The study will test whether 68Ga-PSMA will identify prostate cancer more precisely than normal imaging methods (for example CT, MRI, or bone scan). A more precise identification of the location of the disease is important. Knowing where the disease is located will help to decide on the best course of action to treat the disease. Men who have elevated tumor markers of prostate cancer are eligible for this study. Participants undergo a 68Ga-PSMA PET/CT scan before further treatment. Based on clinical information, including any prior imaging and biopsy/surgery information and follow-up information, we will determine whether 68Ga-PSMA PET/CT imaging was more accurate than the standard imaging. The study team will collect this information for up to 1 year after the 68Ga-PSMA PET/CT scan. The results of the 68Ga-PSMA PET/CT scan will be shared with the participating patients. Also, results will be entered into the participant's medical record and shared with the treating physicians.
Interventions
DRUG68Ga-PSMA
PET/CT imaging with 68Ga-PSMA: 68Ga-PSMA is an investigational radioactive drug that binds to receptors on prostate cancer cells. The intravenously administered drug dose will be about 5 mCi (range 3-7 mCi).
Sponsors
University of Michigan
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
1. Histopathological proven prostate adenocarcinoma. 2. Rising prostate specific antigen (PSA) after definitive therapy with prostatectomy or radiation therapy (external beam or brachytherapy). 1. Post radical prostatectomy (RP) - according to American Urological Association (AUA) recommendation criteria: PSA greater than 0.2 ng/mL measured more than 6 weeks after RP and confirmatory persistent PSA greater than 0.2 ng/mL. 2. Post-radiation therapy - according to ASTRO-Phoenix consensus definition: Nadir + greater than or equal to 2 ng/mL rise in PSA. 3. Karnofsky performance status of ≥ 50. 4. Age ≥ 18. 5. Ability to understand a written informed consent document, and the willingness to sign it.
Exclusion criteria
1. Current investigational therapy for prostate cancer. 2. Unable to lie flat, still or tolerate a PET/CT scan. 3. Prior history of a malignancy within the last 2 years, except skin basal cell or cutaneous superficial squamous cell carcinoma that has not metastasized, and except superficial bladder cancer. 4. Prisoner.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Positive Predictive Value (PPV) of 68Ga PSMA PET/CT for Detecting Prostate Cancer on a Per-patient Basis Confirmed by Histopathology. | Up to 12 months after 68Ga-PSMA scan | Evaluation of the positive predictive value (PPV) (true positives / (true positives + false positives)) of 68Ga-PSMA-11 PET for presence of prostate cancer confirmed by histopathology on a per-patient basis. On a per-patient basis, the PPV of conventional imaging ranges between 30-50%. The null hypothesis is that the PPV at 50% will be tested against the alternative hypothesis that the PPV is greater than 50%. The result of a histopathological examination of a PSMA positive lesion is obtained when available. Such data are collected as a single time point up to 12 months following the scan. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity and PPV on a Per-patient and Per-region-basis of 68Ga-PSMA PET/CT for Detection of Tumor Location. | Up to 12 months after 68Ga-PSMA scan | The sensitivity and PPV of 68Ga-PSMA PET/CT is determined on a per-patient and per-region-basis for the detection of tumor location. Confirmation is obtained by conventional imaging, clinical follow-up, and/or histopathology/biopsy where available. Results of conventional imaging, clinical follow-up, and/or histopathology is collected as a single time point up to 12 months following the scan. |
| Adverse Events of 68Ga-PSMA Administration | 24 - 72 hours post administration | The number of adverse events were determined through clinical assessment and categorized by CTCAE 4.0. |
| Detection Rates on a Per-patient Basis of 68Ga-PSMA-11 PET/CT | 12 months post scan | Scan detection rates (in %) on a per-patient basis are given for specific PSA value ranges (a) 0.2\<0.5, b) 0.5\<1.0, c) 1.0\<2.0, d) 2.0\<5.0, e) \>=5.0 ng/mL. Ideally, the 68Ga-PSMA-11 PET/CT scan detection rate would be 100% at any PSA range. |
| Impact of 68Ga-PSMA-11 PET on Clinical Management in BCR Patients | 2 days to 12 months following the scan. | The results of this outcome measure were evaluated using a treatment plan questionnaire given to the treating physician or practitioner before the scan, at approximately 1 month (2-30 days) after the 68Ga-PSMA-11 PET scan, and at approximately 6 months (range 3 - 12 months) after the 68Ga-PSMA-11 PET scan. The treatment plan questionnaire was provided with 11 choice options. Responses to the questionnaire were compared to determine whether physicians changed their treatment plans following the PET scan. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 68Ga-PSMA Participants in this arm were prostate cancer patients who experienced elevated PSA after definitive therapy with prostatectomy, radiation therapy (external beam or brachytherapy), or focal therapy of the prostate. | 1,181 |
| Physicians Participants were the ordering physicians/practitioners of the patient participants in the 68Ga-PSMA study arm. | 254 |
| Total | 1,435 |
Baseline characteristics
| Characteristic | 68Ga-PSMA | Total | Physicians |
|---|---|---|---|
| Age, Continuous Age | 69.4 years STANDARD_DEVIATION 7 | 69.4 years STANDARD_DEVIATION 7 | — |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 6 Participants | — |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1175 Participants | 1175 Participants | — |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | — |
| Height | 177.5 cm STANDARD_DEVIATION 8.7 | 177.5 cm STANDARD_DEVIATION 8.7 | — |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Asian | 7 Participants | 7 Participants | — |
| Race (NIH/OMB) Black or African American | 99 Participants | 99 Participants | — |
| Race (NIH/OMB) More than one race | 14 Participants | 14 Participants | — |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | — |
| Race (NIH/OMB) White | 1060 Participants | 1060 Participants | — |
| Region of Enrollment United States | 1181 Participants | 1435 Participants | 254 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1181 Participants | 1181 Participants | 0 Participants |
| Weight | 91.2 kg STANDARD_DEVIATION 17.3 | 91.2 kg STANDARD_DEVIATION 17.3 | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1,181 |
| other Total, other adverse events | 2 / 1,181 |
| serious Total, serious adverse events | 1 / 1,181 |
Outcome results
Primary
Positive Predictive Value (PPV) of 68Ga PSMA PET/CT for Detecting Prostate Cancer on a Per-patient Basis Confirmed by Histopathology.
Evaluation of the positive predictive value (PPV) (true positives / (true positives + false positives)) of 68Ga-PSMA-11 PET for presence of prostate cancer confirmed by histopathology on a per-patient basis. On a per-patient basis, the PPV of conventional imaging ranges between 30-50%. The null hypothesis is that the PPV at 50% will be tested against the alternative hypothesis that the PPV is greater than 50%. The result of a histopathological examination of a PSMA positive lesion is obtained when available. Such data are collected as a single time point up to 12 months following the scan.
Time frame: Up to 12 months after 68Ga-PSMA scan
Population: The participants analyzed were all those who had histopathological confirmation. Participants in this arm were prostate cancer patients who experienced elevated PSA after definitive therapy with prostatectomy, radiation therapy (external beam or brachytherapy), or focal therapy of the prostate.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 68Ga-PSMA | Positive Predictive Value (PPV) of 68Ga PSMA PET/CT for Detecting Prostate Cancer on a Per-patient Basis Confirmed by Histopathology. | 87.3 percentage of times value is true |
Comparison: We determined the positive predictive value (PPV) (true positives / (true positives + false positives)) of 68Ga-PSMA-11 PET for presence or absence of prostate cancer confirmed by histopathology on a per-patient basis. On a per-patient basis, the PPV of conventional imaging ranges between 30-50%. The null hypothesis is that the PPV at 50% will be tested against the alternative hypothesis that the PPV is greater than 50%.p-value: <1e-795% CI: [81.58, 100]Exact binomial proportion test
Secondary
Adverse Events of 68Ga-PSMA Administration
The number of adverse events were determined through clinical assessment and categorized by CTCAE 4.0.
Time frame: 24 - 72 hours post administration
Population: Participants in this arm were prostate cancer patients who experienced elevated PSA after definitive therapy with prostatectomy, radiation therapy (external beam or brachytherapy), or focal therapy of the prostate and received a 68Ga-PSMA-11 PET/CT scan.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 68Ga-PSMA | Adverse Events of 68Ga-PSMA Administration | Adverse events | 2 events |
| 68Ga-PSMA | Adverse Events of 68Ga-PSMA Administration | Serious adverse events | 1 events |
Secondary
Detection Rates on a Per-patient Basis of 68Ga-PSMA-11 PET/CT
Scan detection rates (in %) on a per-patient basis are given for specific PSA value ranges (a) 0.2\<0.5, b) 0.5\<1.0, c) 1.0\<2.0, d) 2.0\<5.0, e) \>=5.0 ng/mL. Ideally, the 68Ga-PSMA-11 PET/CT scan detection rate would be 100% at any PSA range.
Time frame: 12 months post scan
Population: Participants in this arm were prostate cancer patients who experienced elevated PSA after definitive therapy with prostatectomy, radiation therapy, or focal therapy of the prostate.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 68Ga-PSMA | Detection Rates on a Per-patient Basis of 68Ga-PSMA-11 PET/CT | PSA range 0.2 - < 0.5 ng/mL. | 55.1 percentage of positive scans |
| 68Ga-PSMA | Detection Rates on a Per-patient Basis of 68Ga-PSMA-11 PET/CT | PSA range 0.5 - < 1.0 ng/mL. | 71.2 percentage of positive scans |
| 68Ga-PSMA | Detection Rates on a Per-patient Basis of 68Ga-PSMA-11 PET/CT | PSA range 1.0 - < 2.0 ng/mL. | 85.5 percentage of positive scans |
| 68Ga-PSMA | Detection Rates on a Per-patient Basis of 68Ga-PSMA-11 PET/CT | PSA range 2.0 - < 5.0 ng/mL. | 91.1 percentage of positive scans |
| 68Ga-PSMA | Detection Rates on a Per-patient Basis of 68Ga-PSMA-11 PET/CT | PSA range 5.0 and above ng/mL. | 95.4 percentage of positive scans |
Secondary
Impact of 68Ga-PSMA-11 PET on Clinical Management in BCR Patients
The results of this outcome measure were evaluated using a treatment plan questionnaire given to the treating physician or practitioner before the scan, at approximately 1 month (2-30 days) after the 68Ga-PSMA-11 PET scan, and at approximately 6 months (range 3 - 12 months) after the 68Ga-PSMA-11 PET scan. The treatment plan questionnaire was provided with 11 choice options. Responses to the questionnaire were compared to determine whether physicians changed their treatment plans following the PET scan.
Time frame: 2 days to 12 months following the scan.
Population: The intention was to count the number of prostate cancer patients and whether their treatment plans changed post scan based on physician survey responses and the participant's electronic medical record. Not all the physicians responded to surveys, and electronic records were not available for all participants, meaning data are missing for some patients.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 68Ga-PSMA | Impact of 68Ga-PSMA-11 PET on Clinical Management in BCR Patients | Change in management from time before the scan | 886 Participants |
| 68Ga-PSMA | Impact of 68Ga-PSMA-11 PET on Clinical Management in BCR Patients | No change in management from time before the scan | 294 Participants |
| 68Ga-PSMA | Impact of 68Ga-PSMA-11 PET on Clinical Management in BCR Patients | Missing Data | 1 Participants |
| Treatment Plans At The End of the Study (One Year Post Scan) | Impact of 68Ga-PSMA-11 PET on Clinical Management in BCR Patients | Change in management from time before the scan | 374 Participants |
| Treatment Plans At The End of the Study (One Year Post Scan) | Impact of 68Ga-PSMA-11 PET on Clinical Management in BCR Patients | No change in management from time before the scan | 594 Participants |
| Treatment Plans At The End of the Study (One Year Post Scan) | Impact of 68Ga-PSMA-11 PET on Clinical Management in BCR Patients | Missing Data | 213 Participants |
Secondary
Sensitivity and PPV on a Per-patient and Per-region-basis of 68Ga-PSMA PET/CT for Detection of Tumor Location.
The sensitivity and PPV of 68Ga-PSMA PET/CT is determined on a per-patient and per-region-basis for the detection of tumor location. Confirmation is obtained by conventional imaging, clinical follow-up, and/or histopathology/biopsy where available. Results of conventional imaging, clinical follow-up, and/or histopathology is collected as a single time point up to 12 months following the scan.
Time frame: Up to 12 months after 68Ga-PSMA scan
Population: Participants analyzed were all those where either conventional imaging, clinical follow-up, or histopathology was available. Participants in this arm were prostate cancer patients who experienced elevated PSA after definitive therapy with prostatectomy, radiation therapy (external beam or brachytherapy), or focal therapy of the prostate.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 68Ga-PSMA | Sensitivity and PPV on a Per-patient and Per-region-basis of 68Ga-PSMA PET/CT for Detection of Tumor Location. | PPV, Per-Participant Basis | 92.3 percentage of times value is true |
| 68Ga-PSMA | Sensitivity and PPV on a Per-patient and Per-region-basis of 68Ga-PSMA PET/CT for Detection of Tumor Location. | Sensitivity, Per-Participant Basis | 95.29 percentage of times value is true |
| 68Ga-PSMA | Sensitivity and PPV on a Per-patient and Per-region-basis of 68Ga-PSMA PET/CT for Detection of Tumor Location. | PPV, prostate or prostate bed | 91.1 percentage of times value is true |
| 68Ga-PSMA | Sensitivity and PPV on a Per-patient and Per-region-basis of 68Ga-PSMA PET/CT for Detection of Tumor Location. | Sensitivity, prostate or prostate bed | 91.72 percentage of times value is true |
| 68Ga-PSMA | Sensitivity and PPV on a Per-patient and Per-region-basis of 68Ga-PSMA PET/CT for Detection of Tumor Location. | PPV, pelvic lymph nodes | 90.78 percentage of times value is true |
| 68Ga-PSMA | Sensitivity and PPV on a Per-patient and Per-region-basis of 68Ga-PSMA PET/CT for Detection of Tumor Location. | Sensitivity, pelvic lymph nodes | 96.97 percentage of times value is true |
| 68Ga-PSMA | Sensitivity and PPV on a Per-patient and Per-region-basis of 68Ga-PSMA PET/CT for Detection of Tumor Location. | PPV, soft tissues | 91.25 percentage of times value is true |
| 68Ga-PSMA | Sensitivity and PPV on a Per-patient and Per-region-basis of 68Ga-PSMA PET/CT for Detection of Tumor Location. | Sensitivity, soft tissues | 93.59 percentage of times value is true |
| 68Ga-PSMA | Sensitivity and PPV on a Per-patient and Per-region-basis of 68Ga-PSMA PET/CT for Detection of Tumor Location. | PPV, bone | 95.17 percentage of times value is true |
| 68Ga-PSMA | Sensitivity and PPV on a Per-patient and Per-region-basis of 68Ga-PSMA PET/CT for Detection of Tumor Location. | Sensitivity, bone | 100 percentage of times value is true |
Comparison: PPV, composite standard, per-patient basis: We determined the positive predictive value (PPV) of 68Ga-PSMA-11 PET for presence of prostate cancer confirmed by conventional imaging, clinical follow-up, and histopathology/biopsy where available. On a per-patient basis, the PPV of conventional imaging ranges between 30-50%. The null hypothesis is that the PPV at 50% will be tested against the alternative hypothesis that the PPV is greater than 50%.p-value: <1e-795% CI: [90, 100]binomial proportion test
Comparison: Sensitivity, composite standard, per-patient basis: We determined the sensitivity of 68Ga-PSMA-11 PET for presence of prostate cancer confirmed by conventional imaging, clinical follow-up, and histopathology/biopsy (composite standard of truth). On a per-patient basis, the sensitivity of conventional imaging ranges between 30-50%. The null hypothesis is that the sensitivity at 50% will be tested against the alternative hypothesis that the sensitivity is greater than 50%.p-value: <1e-795% CI: [93.3, 100]Sensitivity
Comparison: PPV, composite standard, prostate or prostate bed: PPV of 68Ga-PSMA-11 PET for presence of prostate cancer confirmed by conventional imaging, clinical follow-up, and histopathology/biopsy where available (composite standard of truth). In the prostate or prostate bed, the PPV of conventional imaging ranges between 30-50%. The null hypothesis is that the PPV at 50% will be tested against the alternative hypothesis that the PPV is greater than 50%.p-value: <1e-795% CI: [86.2, 100]Exact binomial proportion test
Comparison: Sensitivity, composite standard, prostate/prostate bed: We determined the sensitivity of 68Ga-PSMA-11 PET for presence of prostate cancer confirmed by conventional imaging, clinical follow-up, and histopathology/biopsy (composite standard of truth). In the prostate or prostate bed, the sensitivity of conventional imaging ranges between 30-50%. The null hypothesis is that the sensitivity at 50% will be tested against the alternative hypothesis that the sensitivity is greater than 50%.p-value: <1e-795% CI: [86.74, 100]Exact binomial proportion test
Comparison: PPV, composite standard, pelvic lymph nodes: PPV of 68Ga-PSMA-11 PET for presence of prostate cancer confirmed by conventional imaging, clinical follow-up, and histopathology/biopsy where available (composite standard of truth). In the prostate or prostate bed, the PPV of conventional imaging ranges between 30-50%. The null hypothesis is that the PPV at 50% will be tested against the alternative hypothesis that the PPV is greater than 50%.p-value: <1e-795% CI: [85.74, 100]Exact binomial proportion test
Comparison: Sensitivity, composite standard, pelvic lymph nodes: We determined the sensitivity of 68Ga-PSMA-11 PET for presence of prostate cancer confirmed by conventional imaging, clinical follow-up, and histopathology/biopsy (composite standard of truth). In pelvic lymph nodes, the sensitivity of conventional imaging ranges between 30-50%. The null hypothesis is that the sensitivity at 50% will be tested against the alternative hypothesis that the sensitivity is greater than 50%.p-value: <1e-795% CI: [93.2, 100]Exact binomial proportion test
Comparison: PPV, composite standard, soft tissues: PPV of 68Ga-PSMA-11 PET for presence of prostate cancer confirmed by conventional imaging, clinical follow-up, and histopathology/biopsy where available (composite standard of truth). In soft tissues, the PPV of conventional imaging ranges between 30-50%. The null hypothesis is that the PPV at 50% will be tested against the alternative hypothesis that the PPV is greater than 50%.p-value: <1e-795% CI: [84.19, 100]Exact binomial proportion test
Comparison: Sensitivity, composite standard, soft tissues: We determined the sensitivity of 68Ga-PSMA-11 PET for presence of prostate cancer confirmed by conventional imaging, clinical follow-up, and histopathology/biopsy (composite standard of truth). In soft tissues, the sensitivity of conventional imaging ranges between 30-50%. The null hypothesis is that the sensitivity at 50% will be tested against the alternative hypothesis that the sensitivity is greater than 50%.p-value: <1e-795% CI: [86.99, 100]Exact binomial proportion test
Comparison: PPV, composite standard, bone: PPV of 68Ga-PSMA-11 PET for presence of prostate cancer confirmed by conventional imaging, clinical follow-up, and histopathology/biopsy where available (composite standard of truth). In bone tissues, the PPV of conventional imaging ranges between 30-50%. The null hypothesis is that the PPV at 50% will be tested against the alternative hypothesis that the PPV is greater than 50%.p-value: <1e-795% CI: [91.12, 100]Exact binomial proportion test
Comparison: Sensitivity, composite standard, bone: We determined the sensitivity of 68Ga-PSMA-11 PET for presence of prostate cancer confirmed by conventional imaging, clinical follow-up, and histopathology/biopsy (composite standard of truth). In bone, the sensitivity of conventional imaging ranges between 30-50%. The null hypothesis is that the sensitivity at 50% will be tested against the alternative hypothesis that the sensitivity is greater than 50%.p-value: <1e-795% CI: [97.85, 100]Exact binomial proportion test