Prostate Cancer
Conditions
Keywords
Diagnostic imaging, High-Intensity Focused Ultrasound, HIFU, 18F-Fluciclovine, high resolution diffusion-weighted imaging
Brief summary
This prospective trial aims to determine if enhanced prostate imaging using two novel imaging technologies (high resolution DWI and 18F-fluciclovine PET-MRI) will detect prostate cancers not seen on standard multiparametric prostate MRI in patients considered candidates for focal HIFU.
Detailed description
This is a prospective trial to evaluate the effectiveness of 18F-fluciclovine PET-hrMRI versus standard mpMRI at identifying prostate cancer targets for HIFU therapy. Participants with clinically localized, unilateral high grade prostate cancer (Gleason score 7-10 prostate cancer localized to one lobe on prior biopsies) OR at high risk for having unrecognized high grade prostate cancer (overall Gleason score 6 with \> half of systematic biopsy cores positive and \> 50% of core involvement in at least one core), interested in HIFU would receive both a standard mpMRI and 18F-fluciclovine PET-hrMRI. Participants would then undergo a mapping biopsy using a standard sextant template plus MRI/US-fusion targeted biopsy of any lesion suspicious lesion on mpMRI or PET-hrMRI.
Interventions
DRUG18F-Fluciclovine
Imaging (comparing standard and experimental high resolution diffusion-weighted imaging \[DWI\] MRI with 18F-Fluciclovine)
Sponsors
Blue Earth Diagnostics
Timothy J. Daskivich
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Prostate biopsy consisting of ≥ 10 tissue cores sampled * PSA \</=20 ng/mL * cT1-cT2c * Either overall gleason score \>/= 7 with Gleason grade 4 or 5 component localized to one lobe (i.e. right or left) OR overall Gleason score 6 with \>/= half of systematic biopsy cores positive and \>/= 50% of core involvement in at least one core * Patient considering focal HIFU therapy
Exclusion criteria
* Previous local therapy for prostate cancer * Inability to receive PET tracer * Inability to receive MRI * Suggestion of extracapsular extension or seminal vesicle invasion on imaging * Estimated creatinine clearance \<45 mL/min (Cockcroft-Gault equation) * Any other condition which, in the investigator's option, may make the patient a poor candidate for participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Biopsy-proven Cancers (Gleason 6+) That Standard Imaging (mpMRI) Would Have Missed Compared With High Resolution Diffusion-weighted Imaging (DWI) PET-hrMRI on Mapping MRI. | At time of post-imaging biopsy | A Gleason score of 6 is low grade, 7 is intermediate grade, and a score of 8 to 10 is high grade cancer. The Prostate Imaging Reporting and Data System (PI-RADS) is used to report how likely it is that a suspicious area is a clinically significant cancer. PI-RADS scores range from 1 (most likely not cancer) to 5 (very suspicious). Difference between sensitivities to identify prostate lesions. This is analyzed by the number of biopsy-proven cancerous zones (Gleason 6+) that mpMRI missed compared to PET or hrMRI (PIRADS) compared as follows: mpMRI vs hrMRI and PET (PIRADS 3-5 & Gleason 7+) mpMRI vs hrMRI or PET (PIRADS 3-5 & Gleason 7+) mpMRI vs hrMRI and PET (PIRADS 4-5 & Gleason 7+) mpMRI vs hrMRI or PET (PIRADS 4-5 & Gleason 7+) mpMRI vs hrMRI and PET (PIRADS 3-5 & Gleason 6+) mpMRI vs hrMRI or PET (PIRADS 3-5 & Gleason 6+) mpMRI vs hrMRI and PET (PIRADS 4-5 & Gleason 6+) mpMRI vs hrMRI or PET (PIRADS 4-5 & Gleason 6+) |
| Number of Biopsy-proven Cancers (Gleason 7+) That Standard Imaging (mpMRI) Would Have Missed Compared With High Resolution Diffusion-weighted Imaging (DWI) PET-hrMRI on Mapping MRI. | At time of post-imaging biopsy | A Gleason score of 6 is low grade, 7 is intermediate grade, and a score of 8 to 10 is high grade cancer. The Prostate Imaging Reporting and Data System (PI-RADS) is used to report how likely it is that a suspicious area is a clinically significant cancer. PI-RADS scores range from 1 (most likely not cancer) to 5 (very suspicious). Difference between sensitivities to identify prostate lesions. This is analyzed by the number of biopsy-proven cancerous zones (Gleason 7+) that mpMRI missed compared to PET or hrMRI (PIRADS) compared as follows: mpMRI vs hrMRI and PET (PIRADS 3-5 & Gleason 7+) mpMRI vs hrMRI or PET (PIRADS 3-5 & Gleason 7+) mpMRI vs hrMRI and PET (PIRADS 4-5 & Gleason 7+) mpMRI vs hrMRI or PET (PIRADS 4-5 & Gleason 7+) mpMRI vs hrMRI and PET (PIRADS 3-5 & Gleason 6+) mpMRI vs hrMRI or PET (PIRADS 3-5 & Gleason 6+) mpMRI vs hrMRI and PET (PIRADS 4-5 & Gleason 6+) mpMRI vs hrMRI or PET (PIRADS 4-5 & Gleason 6+) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Negative Biopsy Rate (Number of Participants With Negative Biopsy) | 6 months following standard HIFU therapy | A Gleason score of 6 is low grade, 7 is intermediate grade, and a score of 8 to 10 is high grade cancer. The Prostate Imaging Reporting and Data System (PI-RADS) is used to report how likely it is that a suspicious area is a clinically significant cancer. PI-RADS scores range from 1 (most likely not cancer) to 5 (very suspicious). Following the tumor mapping study, patients with high grade disease (i.e. Gleason grade 4 or 5) in one lobe undergo hemigland or focal HIFU of that lobe. Patients would then undergo repeat prostate biopsy to assess the negative biopsy rate in the treated region. |
| Rate of High Grade Cancer (Number of Patients With High Grade Cancer) | 6 months following standard HIFU therapy | A Gleason score of 6 is low grade, 7 is intermediate grade, and a score of 8 to 10 is high grade cancer. The Prostate Imaging Reporting and Data System (PI-RADS) is used to report how likely it is that a suspicious area is a clinically significant cancer. PI-RADS scores range from 1 (most likely not cancer) to 5 (very suspicious). Following the tumor mapping study, patients with high grade disease (i.e. Gleason grade 4 or 5) in one lobe undergo hemigland or focal HIFU of that lobe. Patients would then undergo repeat prostate biopsy to assess the absence of Gleason grade 4 or 5 in the untreated region. |
Countries
United States
Participant flow
Recruitment details
Opened to accrual on 12/07/2017 with first subject enrolled on study 12/18/2017. A total of 21 patients consented, one withdrew consent prior to intervention and was replaced, 13 were evaluable for primary outcome measure, however 11 subjects of the total target accrual of 20 subjects completed study with the last subject off treatment/off study as of 1/8/2020.
Participants by arm
| Arm | Count |
|---|---|
| 18F-Fluciclovine 10mCi +/-20% 18F-fluciclovine injection
18F-Fluciclovine: Imaging (comparing standard and experimental high resolution diffusion-weighted imaging \[DWI\] MRI with 18F-Fluciclovine) | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Ineligible (incomplete post-HIFU) | 7 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | 18F-Fluciclovine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Age, Continuous | 67.8 years STANDARD_DEVIATION 7.54 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 13 |
| other Total, other adverse events | 0 / 13 |
| serious Total, serious adverse events | 1 / 13 |
Outcome results
Primary
Number of Biopsy-proven Cancers (Gleason 6+) That Standard Imaging (mpMRI) Would Have Missed Compared With High Resolution Diffusion-weighted Imaging (DWI) PET-hrMRI on Mapping MRI.
A Gleason score of 6 is low grade, 7 is intermediate grade, and a score of 8 to 10 is high grade cancer. The Prostate Imaging Reporting and Data System (PI-RADS) is used to report how likely it is that a suspicious area is a clinically significant cancer. PI-RADS scores range from 1 (most likely not cancer) to 5 (very suspicious). Difference between sensitivities to identify prostate lesions. This is analyzed by the number of biopsy-proven cancerous zones (Gleason 6+) that mpMRI missed compared to PET or hrMRI (PIRADS) compared as follows: mpMRI vs hrMRI and PET (PIRADS 3-5 & Gleason 7+) mpMRI vs hrMRI or PET (PIRADS 3-5 & Gleason 7+) mpMRI vs hrMRI and PET (PIRADS 4-5 & Gleason 7+) mpMRI vs hrMRI or PET (PIRADS 4-5 & Gleason 7+) mpMRI vs hrMRI and PET (PIRADS 3-5 & Gleason 6+) mpMRI vs hrMRI or PET (PIRADS 3-5 & Gleason 6+) mpMRI vs hrMRI and PET (PIRADS 4-5 & Gleason 6+) mpMRI vs hrMRI or PET (PIRADS 4-5 & Gleason 6+)
Time frame: At time of post-imaging biopsy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 18F-Fluciclovine | Number of Biopsy-proven Cancers (Gleason 6+) That Standard Imaging (mpMRI) Would Have Missed Compared With High Resolution Diffusion-weighted Imaging (DWI) PET-hrMRI on Mapping MRI. | Number of biopsy-proven cancers (Gleason 6+) that mpMRI missed compared to PET or hrMRI (PIRADS 3-5) | 5 Total biopsy-proven cancers (Gleason 6+) |
| 18F-Fluciclovine | Number of Biopsy-proven Cancers (Gleason 6+) That Standard Imaging (mpMRI) Would Have Missed Compared With High Resolution Diffusion-weighted Imaging (DWI) PET-hrMRI on Mapping MRI. | Number of biopsy-proven cancers (Gleason 6+) that mpMRI missed compared to PET & hrMRI (PIRADS 3-5) | 1 Total biopsy-proven cancers (Gleason 6+) |
| 18F-Fluciclovine | Number of Biopsy-proven Cancers (Gleason 6+) That Standard Imaging (mpMRI) Would Have Missed Compared With High Resolution Diffusion-weighted Imaging (DWI) PET-hrMRI on Mapping MRI. | Number of biopsy-proven cancers (Gleason 6+) that mpMRI missed compared to PET or hrMRI (PIRADS 4-5) | 4 Total biopsy-proven cancers (Gleason 6+) |
| 18F-Fluciclovine | Number of Biopsy-proven Cancers (Gleason 6+) That Standard Imaging (mpMRI) Would Have Missed Compared With High Resolution Diffusion-weighted Imaging (DWI) PET-hrMRI on Mapping MRI. | Number of biopsy-proven cancers (Gleason 6+) that mpMRI missed compared to PET & hrMRI (PIRADS 4-5) | 1 Total biopsy-proven cancers (Gleason 6+) |
Comparison: mpMRI vs hrMRI and PET (PIRADS 3-5 \& Gleason 6+)p-value: 0.05695% CI: [0.19, 0.46]Durkalski's Chi-square test
Comparison: mpMRI vs hrMRI or PET (PIRADS 3-5 \& Gleason 6+)p-value: 0.5695% CI: [0.44, 0.78]Durkalski's Chi-square test
Comparison: mpMRI vs hrMRI and PET (PIRADS 4-5 \& Gleason 6+)p-value: 0.0695% CI: [0.17, 0.47]Durkalski's Chi-square test
Comparison: mpMRI vs hrMRI or PET (PIRADS 4-5 \& Gleason 6+)p-value: 0.08395% CI: [0.39, 0.74]Durkalski's Chi-square test
Primary
Number of Biopsy-proven Cancers (Gleason 7+) That Standard Imaging (mpMRI) Would Have Missed Compared With High Resolution Diffusion-weighted Imaging (DWI) PET-hrMRI on Mapping MRI.
A Gleason score of 6 is low grade, 7 is intermediate grade, and a score of 8 to 10 is high grade cancer. The Prostate Imaging Reporting and Data System (PI-RADS) is used to report how likely it is that a suspicious area is a clinically significant cancer. PI-RADS scores range from 1 (most likely not cancer) to 5 (very suspicious). Difference between sensitivities to identify prostate lesions. This is analyzed by the number of biopsy-proven cancerous zones (Gleason 7+) that mpMRI missed compared to PET or hrMRI (PIRADS) compared as follows: mpMRI vs hrMRI and PET (PIRADS 3-5 & Gleason 7+) mpMRI vs hrMRI or PET (PIRADS 3-5 & Gleason 7+) mpMRI vs hrMRI and PET (PIRADS 4-5 & Gleason 7+) mpMRI vs hrMRI or PET (PIRADS 4-5 & Gleason 7+) mpMRI vs hrMRI and PET (PIRADS 3-5 & Gleason 6+) mpMRI vs hrMRI or PET (PIRADS 3-5 & Gleason 6+) mpMRI vs hrMRI and PET (PIRADS 4-5 & Gleason 6+) mpMRI vs hrMRI or PET (PIRADS 4-5 & Gleason 6+)
Time frame: At time of post-imaging biopsy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 18F-Fluciclovine | Number of Biopsy-proven Cancers (Gleason 7+) That Standard Imaging (mpMRI) Would Have Missed Compared With High Resolution Diffusion-weighted Imaging (DWI) PET-hrMRI on Mapping MRI. | Number of biopsy-proven cancers (Gleason 7+) that mpMRI missed compared to PET or hrMRI (PIRADS 3-5) | 1 Total biopsy-proven cancers (Gleason 7+) |
| 18F-Fluciclovine | Number of Biopsy-proven Cancers (Gleason 7+) That Standard Imaging (mpMRI) Would Have Missed Compared With High Resolution Diffusion-weighted Imaging (DWI) PET-hrMRI on Mapping MRI. | Number of biopsy-proven cancers (Gleason 7+) that mpMRI missed compared to PET & hrMRI (PIRADS 3-5) | 1 Total biopsy-proven cancers (Gleason 7+) |
| 18F-Fluciclovine | Number of Biopsy-proven Cancers (Gleason 7+) That Standard Imaging (mpMRI) Would Have Missed Compared With High Resolution Diffusion-weighted Imaging (DWI) PET-hrMRI on Mapping MRI. | Number of biopsy-proven cancers (Gleason 7+) that mpMRI missed compared to PET or hrMRI (PIRADS 4-5) | 1 Total biopsy-proven cancers (Gleason 7+) |
| 18F-Fluciclovine | Number of Biopsy-proven Cancers (Gleason 7+) That Standard Imaging (mpMRI) Would Have Missed Compared With High Resolution Diffusion-weighted Imaging (DWI) PET-hrMRI on Mapping MRI. | Number of biopsy-proven cancers (Gleason 7+) that mpMRI missed compared to PET & hrMRI (PIRADS 4-5) | 1 Total biopsy-proven cancers (Gleason 7+) |
Comparison: mpMRI vs hrMRI and PET (PIRADS 3-5 \& Gleason 7+)p-value: 0.09695% CI: [0.26, 0.65]Durkalski's Chi-square test
Comparison: mpMRI vs hrMRI or PET (PIRADS 3-5 \& Gleason 7+)p-value: 0.31795% CI: [0.46, 0.9]Durkalski's Chi-square test
Comparison: mpMRI vs hrMRI and PET (PIRADS 4-5 \& Gleason 7+)p-value: 0.06395% CI: [0.23, 0.66]Durkalski's Chi-square test
Comparison: mpMRI vs hrMRI or PET (PIRADS 4-5 \& Gleason 7+)p-value: 0.31795% CI: [0.46, 0.9]Durkalski's Chi-square test
Secondary
Negative Biopsy Rate (Number of Participants With Negative Biopsy)
A Gleason score of 6 is low grade, 7 is intermediate grade, and a score of 8 to 10 is high grade cancer. The Prostate Imaging Reporting and Data System (PI-RADS) is used to report how likely it is that a suspicious area is a clinically significant cancer. PI-RADS scores range from 1 (most likely not cancer) to 5 (very suspicious). Following the tumor mapping study, patients with high grade disease (i.e. Gleason grade 4 or 5) in one lobe undergo hemigland or focal HIFU of that lobe. Patients would then undergo repeat prostate biopsy to assess the negative biopsy rate in the treated region.
Time frame: 6 months following standard HIFU therapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 18F-Fluciclovine | Negative Biopsy Rate (Number of Participants With Negative Biopsy) | 11 Participants |
Secondary
Rate of High Grade Cancer (Number of Patients With High Grade Cancer)
A Gleason score of 6 is low grade, 7 is intermediate grade, and a score of 8 to 10 is high grade cancer. The Prostate Imaging Reporting and Data System (PI-RADS) is used to report how likely it is that a suspicious area is a clinically significant cancer. PI-RADS scores range from 1 (most likely not cancer) to 5 (very suspicious). Following the tumor mapping study, patients with high grade disease (i.e. Gleason grade 4 or 5) in one lobe undergo hemigland or focal HIFU of that lobe. Patients would then undergo repeat prostate biopsy to assess the absence of Gleason grade 4 or 5 in the untreated region.
Time frame: 6 months following standard HIFU therapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 18F-Fluciclovine | Rate of High Grade Cancer (Number of Patients With High Grade Cancer) | 1 Participants |