Genital Diseases, Male, Genital Neoplasms, Male, Neoplasms, Neoplasms by Site, Prostatic Disease, Prostatic Neoplasms, Urogenital Neoplasms
Conditions
Keywords
Diagnostic imaging, High-Intensity Focused Ultrasound, HIFU, 18F-PSMA, 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-PSMA 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-PSMA 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-PSMA 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-PSMA
Imaging (comparing standard and experimental high resolution diffusion-weighted imaging \[DWI\] MRI with 18F-PSMA) Other Names: 18F-DCFPyL Injection prostate-cancer-specific radiotracer
Sponsors
Alessandro D'Agnolo
Progenics Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Patients are identified by investigator and enrolled in Arm 1 (HIFU) or Arm 2 (RP)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Biopsy consisting of ≥ 10 tissue cores sampled 2. PSA \<20 ng/mL (for HIFU arm only) 3. cT1-cT2c 4. 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 (for HIFU arm only) 5. Patient considering focal HIFU therapy or robotic radical prostatectomy
Exclusion criteria
1. Previous local therapy for prostate cancer 2. Inability to receive PET tracer 3. Inability to receive MRI 4. Estimated glomerular filtration rate (GFR) \<15 mL/min/1.73 m2 5. 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 |
|---|---|---|
| Primary Endpoint (HIFU): Identification of New Cancers | At time of pre-HIFU biopsy | The grade of the cancer is assessed by biopsy prior to HIFU. Systematic and targeted prostate biopsies assess presence or absence of cancer in each zone of the prostate, including both systematic and targeted zones. Each zone with cancer is graded using the Gleason score (range 6-10, with higher scores associated with more aggressive disease). The primary outcome is for detection of any additional cancer with advanced imaging techniques of hrMRI or PSMA-PET MRI over standard multiparametric MRI. Any cancer is defined as "Gleason 6 or higher." We also did an exploratory analysis looking at detection of additional cancers with Gleason scores of 7 or higher. |
| Primary Endpoint (HIFU): | preoperative PET-hrMRI prior to prostatectomy, less than 3 weeks before surgery | The primary endpoint of the Phase II study is to assess the number of participants with biopsy-proven cancers that mpMRI would have missed compared with hrMRI and/or F18-PSMA PET. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Endpoint (HIFU): | 6 months following standard HIFU therapy | Negative biopsy rate on systematic and targeted biopsy 6 months following HIFU therapy. Data presented are from both systematic + targeted biopsy as a single unit. For example, a positive biopsy from a given area of the prostate could have come from either systematic or targeted cores. |
| Secondary Endpoint (Prostatectomy): | 6 months following standard HIFU therapy | Specificity of hrMRI, F18-PSMA PET and mpMRI for detecting all tumors and metastasis at 6 months follow up. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAlessandro D'Agnolo, MD
Cedars-Sinai Medical Center
Participant flow
Recruitment details
The trial opened to accrual on 04/06/2021 with first subject enrolled on study 04/06/2021. Recruitment occurred at Cedars-Sinai Medical Center.
Participants by arm
| Arm | Count |
|---|---|
| ARM 1 (HIFU) - 18F-PSMA 10 mCi ±20% F18-PSMA injection
18F-PSMA: Imaging (comparing standard and experimental high resolution diffusion-weighted imaging \[DWI\] MRI with 18F-PSMA)
Other Names:
18F-DCFPyL Injection prostate-cancer-specific radiotracer | 24 |
| ARM 2 (RP) - 18F-PSMA 10 mCi ±20% F18-PSMA injection
18F-PSMA: Imaging (comparing standard and experimental high resolution diffusion-weighted imaging \[DWI\] MRI with 18F-PSMA)
Other Names:
18F-DCFPyL Injection prostate-cancer-specific radiotracer | 32 |
| Total | 56 |
Baseline characteristics
| Characteristic | ARM 1 (HIFU) - 18F-PSMA | ARM 2 (RP) - 18F-PSMA | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 14 Participants | 15 Participants | 29 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 17 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 28 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 7 Participants | 12 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 15 Participants | 23 Participants | 38 Participants |
| Region of Enrollment United States | 24 participants | 32 participants | 56 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 24 Participants | 32 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 32 |
| other Total, other adverse events | 3 / 24 | 5 / 32 |
| serious Total, serious adverse events | 1 / 24 | 4 / 32 |
Outcome results
Primary
Primary Endpoint (HIFU): Identification of New Cancers
The grade of the cancer is assessed by biopsy prior to HIFU. Systematic and targeted prostate biopsies assess presence or absence of cancer in each zone of the prostate, including both systematic and targeted zones. Each zone with cancer is graded using the Gleason score (range 6-10, with higher scores associated with more aggressive disease). The primary outcome is for detection of any additional cancer with advanced imaging techniques of hrMRI or PSMA-PET MRI over standard multiparametric MRI. Any cancer is defined as Gleason 6 or higher. We also did an exploratory analysis looking at detection of additional cancers with Gleason scores of 7 or higher.
Time frame: At time of pre-HIFU biopsy
Population: The number of participants analyzed is 32 and not 29, because some participants switched over to the RP arm after already completing study intervention (imaging).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ARM 1 (HIFU) - 18F-PSMA | Primary Endpoint (HIFU): Identification of New Cancers | Gleason 6+ | 85 biopsy-proven cancerous zones |
| ARM 1 (HIFU) - 18F-PSMA | Primary Endpoint (HIFU): Identification of New Cancers | Gleason 7+ | 49 biopsy-proven cancerous zones |
Primary
Primary Endpoint (Prostatectomy):
To determine the sensitivity in detection of prostatic carcinoma of novel imaging modalities of hrMRI and/or F18-PSMA PET compared to reference standard mpMRI in patients scheduled to undergo radical prostatectomy.
Time frame: preoperative PET-hrMRI prior to prostatectomy, less than 3 weeks before surgery
Secondary
Secondary Endpoint (HIFU):
Negative biopsy rate on systematic and targeted biopsy 6 months following HIFU therapy. Data presented are from both systematic + targeted biopsy as a single unit. For example, a positive biopsy from a given area of the prostate could have come from either systematic or targeted cores.
Time frame: 6 months following standard HIFU therapy
Population: Negative for any cancer in treated area, including high and low grade cancer 17/22 (77.3%) Negative for high-grade cancer in treated area 18/22 (81.8%)~There were 4/22 patients who had high grade cancer in the treated area, and one patient who had low grade cancer in the treated area. Hence, 18/22 were negative for high grade cancer in the treated area while 17/22 were negative for both high grade or low grade cancer.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ARM 1 (HIFU) - 18F-PSMA | Secondary Endpoint (HIFU): | Negative for any cancer in treated area, including high and low grade cancer | 17 Participants |
| ARM 1 (HIFU) - 18F-PSMA | Secondary Endpoint (HIFU): | Negative for high-grade cancer in treated area | 18 Participants |
Secondary
Secondary Endpoint (Prostatectomy):
Specificity of hrMRI, F18-PSMA PET and mpMRI for detecting all tumors and metastasis at 6 months follow up.
Time frame: 6 months following standard HIFU therapy
Other Pre-specified
Exploratory Endpoint:
RNAseq transcriptome analysis of lesions that are positive on mapping biopsy. Sensitivity and specificity of PET-hrMRI for detecting all tumors detected on prostatectomy pathology.
Time frame: After study completion, an average of 6 months