Prostate Cancer
Conditions
Keywords
prostate cancer
Brief summary
This is a study primarily comparing Magnetic Resonance Imaging (MRI) alone to Positron Emission Tomography (PET)/MRI using an experimental tracer, 68Ga-PSMA-HBED-CC, among men with prostate cancer or prostatic cancer recurrence/metastasis. It is hypothesized that this comparison will demonstrate that PET using the tracer, 68Ga-PSMA-HBED-CC, is more sensitive than MRI alone. Potential subjects who cannot undergo MRI may undergo PET/CT instead.
Detailed description
This is a multi-reader methodological study comparing the diagnostic value of 68Ga-PSMA-HBED-CC PET/CT or 68Ga-PSMA-HBED-CC PET/MRI over MRI alone, using histologic confirmation or serial follow-up for up to 2 years as the gold standard for determination of primary prostate cancer or prostatic cancer recurrence/metastasis. It is hypothesized that this will demonstrate the superiority of 68Ga-PSMA-HBED-CC PET to MRI for sensitivity, and the non-inferiority of 68Ga-PSMA-HBED-CC PET to MRI for specificity.This is a paired, case-control design that is appropriate to statistically evaluate the difference in sensitivity and specificity between the two imaging modalities. Therefore, the estimation of population prevalence is not a study objective, and estimation of clinical utility through calculation of positive and negative predictive values is not appropriate. Imaging studies and follow up subject scans will be organized so that a panel of independent readers will evaluate the MRI and PET studies to assess the level of suspicion for prostate cancer.
Interventions
DRUGPET/MRI with Gallium-68 labeled PSMA-HBED-CC
Subjects have one visit, during which they will undergo one PET/MRI with the study drug, Gallium-68 labeled PSMA-HBED-CC, a radiopharmaceutical
DRUGMultiple PET/MRI with Gallium-68 labeled PSMA-HBED-CC
Subjects have two visits (the second visit being optional) within two years. During each visit, they will undergo one PET/MRI with the study drug, Gallium-68 labeled PSMA-HBED-CC, a radiopharmaceutical
DRUGPET/CT with Gallium-68 labeled PSMA-HBED-CC
Subjects have one visit, during which they will undergo one PET/CT with the study drug, Gallium-68 labeled PSMA-HBED-CC, a radiopharmaceutical
Sponsors
Cancer Research & Treatment Fund, Inc.
Weill Medical College of Cornell University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
NONE
Intervention model description
Subjects may be assigned to one of three groups, each with a different intervention in terms of either mode or frequency
Eligibility
Sex/Gender
MALE
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male aged 21 years or older. 2. Ability to provide signed informed consent and willingness to comply with protocol requirements. 3. Pathologic confirmation of adenocarcinoma of the prostate gland or high clinical suspicion (PSA \> 4 ng/mL, or PSA density \> 0.15 ng/mL2, or PSA doubling time \< 2 years). 4. Meet one of the following 5 criteria 1. Planned for surgical extirpation, which may or may not include lymph node dissection (high risk primary disease) 2. Planned for targeted biopsy of primary lesion 3. Conventional imaging equivocal or suggestive of prostate cancer metastasis/es 4. Planned focal therapy (with or without radiation therapy) with serial follow-up 5. Elevated PSA with no conventional imaging suggestive of metastatic or recurrent disease 5. a. If part of PET/MRI cohort, subject will undergo clinically indicated MRI imaging prior to treatment. Or b. If part of PET/CT cohort, subject will have had clinically indicated MRI within 3 months prior to treatment. 6. Participants must agree to use an acceptable form of birth control throughout the study period. Participants must use condoms for a period of seven days after each injection, if engaged in sexual activity.
Exclusion criteria
1. Clinical and/or technical factors that would compromise statistical analysis of the PET and/or MRI. 2. If part of PET/MRI cohort and patient cohort 3 or 5, subject does not plan to have a prescribed abdomen and pelvis MRI 3. If part of PET/MRI cohort and patient cohort 1, 2 or 4, subject does not plan to have a prescribed pelvis MRI 4. If part of PET/CT cohort and patient cohort 3 or 5, subject does not have previous MR imaging of abdomen and pelvis 5. If part of PET/CT cohort and patient cohort 1, 2 or 4, subject does not have previous MR imaging of pelvis 6. If part of PET/CT cohort, investigator review determines that previous MR images do not meet institutional quality standards 7. If part of PET/MRI cohort, contraindications to MRI 8. Contraindications to PSMA IV administration 9. Other unspecified reasons that, in the opinion of investigators, make the subject unsuitable for enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Pathologic Lesions Detected by PSMA PET and PET/CT Compared to MP MRI | At each visit, immediately after administration of the study drug, approximately 2-3 hours; with up to two visits within 2 years or less | A scan was considered positive if the clinical interpretation was suspicious based on the clinical judgement of the reader. |
| Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region Stratified by PSA Level | At each visit, immediately after administration of the study drug, approximately 2-3 hours; with up to two visits within 2 years or less | Patients were divided into subgroups based on their PSA levels and primary treatment modality. The primary treatment modality subgroups were post radical prostatectomy, post radiation therapy, and post radical prostatectomy and radiation therapy. 109 subjects out of 273 enrolled have data reported. Multiple patients sought care elsewhere and a small number of subjects had 2-year follow-up. This lead to a smaller analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region | At each visit, immediately after administration of the study drug, approximately 2-3 hours; with up to two visits within 2 years or less | True positive rates for detecting lesions between PSMA PET/MRI and MP MRI in various anatomical locations were compared, including prostate/prostatic bed, N1 lymph nodes, N2 lymph nodes, and osseous lesions. Other anatomical sites are other than bone, node, and prostate. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Biochemical Recurrence These are males who were referred because of a rising PSA after definitive treatment for prostate cancer. All subjects underwent PSMA PET and MRI from skull base to upper thighs as per convention. Participants received a single IV dose of 4 mCi (148 MBq) +/- 10% of 68Ga-PSMA-HBED-CC (study drug) followed by a PET/MRI scan, 90 min after injection. | 114 |
| Total | 114 |
Baseline characteristics
| Characteristic | Biochemical Recurrence | — |
|---|---|---|
| Age, Continuous | 69 years | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 114 participants | — |
| Sex: Female, Male Female | 0 Participants | — |
| Sex: Female, Male Male | 114 Participants | — |
| Stratification Based on PSA Levels 0 - <0.2 ng/ml | 23 Participants | — |
| Stratification Based on PSA Levels 0.2 <0.5 ng/ml | 33 Participants | — |
| Stratification Based on PSA Levels 0.5 - 2.0 ng/ml | 28 Participants | — |
| Stratification Based on PSA Levels >2.0 ng/ml | 28 Participants | — |
| Stratification Based on PSA Levels PSA Levels Unavailable | 2 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 273 | 0 / 273 | 0 / 1 | 0 / 0 |
| other Total, other adverse events | 0 / 273 | 0 / 273 | 0 / 1 | 0 / 0 |
| serious Total, serious adverse events | 0 / 273 | 0 / 273 | 0 / 1 | 0 / 0 |
Outcome results
Primary
Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region Stratified by PSA Level
Patients were divided into subgroups based on their PSA levels and primary treatment modality. The primary treatment modality subgroups were post radical prostatectomy, post radiation therapy, and post radical prostatectomy and radiation therapy. 109 subjects out of 273 enrolled have data reported. Multiple patients sought care elsewhere and a small number of subjects had 2-year follow-up. This lead to a smaller analysis.
Time frame: At each visit, immediately after administration of the study drug, approximately 2-3 hours; with up to two visits within 2 years or less
Population: Overall number of participants analyzed includes all participants who underwent MRI regardless of whether a pathologic lesion was identified.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PSMA PET/MRI and PET/CT Scan | Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region Stratified by PSA Level | PSA Levels 0 to < 0.2 ng/mL | 10 lesions |
| PSMA PET/MRI and PET/CT Scan | Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region Stratified by PSA Level | PSA Levels 0.5 to 2.0 ng/mL | 25 lesions |
| PSMA PET/MRI and PET/CT Scan | Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region Stratified by PSA Level | PSA Levels 0.2 to < 0.5 ng/mL | 22 lesions |
| PSMA PET/MRI and PET/CT Scan | Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region Stratified by PSA Level | PET/MRI: PSA Levels > 2.0 ng/mL | 35 lesions |
| PSMA PET/MRI and PET/CT Scan | Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region Stratified by PSA Level | Total Number of Lesions | 92 lesions |
| MRI Scan | Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region Stratified by PSA Level | PET/MRI: PSA Levels > 2.0 ng/mL | 18 lesions |
| MRI Scan | Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region Stratified by PSA Level | Total Number of Lesions | 47 lesions |
| MRI Scan | Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region Stratified by PSA Level | PSA Levels 0 to < 0.2 ng/mL | 0 lesions |
| MRI Scan | Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region Stratified by PSA Level | PSA Levels 0.2 to < 0.5 ng/mL | 19 lesions |
| MRI Scan | Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region Stratified by PSA Level | PSA Levels 0.5 to 2.0 ng/mL | 10 lesions |
p-value: <0.000195% CI: [0.3, 0.53]McNemar
Primary
Number of Subjects With Pathologic Lesions Detected by PSMA PET and PET/CT Compared to MP MRI
A scan was considered positive if the clinical interpretation was suspicious based on the clinical judgement of the reader.
Time frame: At each visit, immediately after administration of the study drug, approximately 2-3 hours; with up to two visits within 2 years or less
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PSMA PET/MRI and PET/CT Scan | Number of Subjects With Pathologic Lesions Detected by PSMA PET and PET/CT Compared to MP MRI | 63 Participants |
| MRI Scan | Number of Subjects With Pathologic Lesions Detected by PSMA PET and PET/CT Compared to MP MRI | 37 Participants |
Secondary
Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region
True positive rates for detecting lesions between PSMA PET/MRI and MP MRI in various anatomical locations were compared, including prostate/prostatic bed, N1 lymph nodes, N2 lymph nodes, and osseous lesions. Other anatomical sites are other than bone, node, and prostate.
Time frame: At each visit, immediately after administration of the study drug, approximately 2-3 hours; with up to two visits within 2 years or less
Population: Overall number of participants analyzed includes all participants who underwent MRI regardless of whether a pathologic lesion was identified.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PSMA PET/MRI and PET/CT Scan | Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region | N2 lymph nodes | 20 lesions |
| PSMA PET/MRI and PET/CT Scan | Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region | Prostate | 3 lesions |
| PSMA PET/MRI and PET/CT Scan | Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region | N1 lymph nodes | 34 lesions |
| PSMA PET/MRI and PET/CT Scan | Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region | Prostatic Bed | 8 lesions |
| PSMA PET/MRI and PET/CT Scan | Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region | Osseous | 24 lesions |
| PSMA PET/MRI and PET/CT Scan | Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region | Other Anatomical Sites | 3 lesions |
| PSMA PET/MRI and PET/CT Scan | Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region | Total Number of Lesions | 92 lesions |
| MRI Scan | Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region | Other Anatomical Sites | 1 lesions |
| MRI Scan | Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region | Total Number of Lesions | 47 lesions |
| MRI Scan | Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region | N1 lymph nodes | 11 lesions |
| MRI Scan | Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region | N2 lymph nodes | 7 lesions |
| MRI Scan | Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region | Osseous | 14 lesions |
| MRI Scan | Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region | Prostate | 7 lesions |
| MRI Scan | Number of Pathological Lesions Detected by PSMA PET/MRI and PET/CT Compared to MP MRI in Prostate Cancer Patients With Biochemical Recurrence by Anatomical Region | Prostatic Bed | 7 lesions |