Study to Evaluate 99mTc-MIP-1404 SPECT/CT Imaging in Men With Biopsy Proven Low-Grade Prostate Cancer

Study Overview
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Brief Summary
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99mTc-MIP-1404 is a radioactive diagnostic imaging agent indicated for imaging men with newly diagnosed prostate cancer whose biopsy indicates a histopathologic Gleason Score of ≤ 3+4 severity who are candidates for active surveillance and are undergoing voluntary radical prostatectomy (RP) [Cohort A] or routine prostate biopsy [Cohort B]. This Phase 3 study is designed to evaluate the specificity and sensitivity of 99mTc-MIP-1404 SPECT/CT imaging to correctly identify subjects with previously unknown clinically significant prostate cancer.

Detailed Description
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This is a multi-center, multi-reader, open-label trial, comparing 99mTc-MIP-1404 SPECT/CT imaging in men who have had a diagnostic trans-rectal ultrasound (TRUS) guided biopsy with a histopathologic finding of Gleason score ≤3+4 who are candidates for active surveillance and are undergoing routine biopsy or voluntary RP with or without a pelvic lymph node dissection (PLND). This study will evaluate the sensitivity and specificity of 99mTc-MIP-1404 SPECT/CT image assessments to correctly identify subjects with previously unknown clinically significant prostate cancer in two cohorts: (1) Low grade prostate cancer who have elected to undergo RP [Cohort A]; and (2) very low risk (VLR) prostate cancer per 2016 NCCN Guidelines who are scheduled to undergo routine prostate biopsy [Cohort B]. Subjects will receive a single dose of 99mTc-MIP-1404 Injection (study drug) followed by whole body planar and SPECT/CT (pelvic) imaging 3-6 hours after injection. In accordance with standard of care procedures, subjects will undergo either voluntary RP [Cohort A] or prostate biopsy [Cohort B] within 42 days after study drug dosing. 99mTc-MIP-1404 image data will be collected by a central imaging core laboratory and evaluated for visible uptake within the prostate gland. These findings will then be compared against central histopathology as the truth standard. The central imaging core lab independent readers for the SPECT/CT scans will be blinded to all clinical data, including pathology results. Likewise, central pathologists are to remain blinded to all clinical data, including imaging results.

Official Title
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A Phase 3 Study to Evaluate the Safety and Efficacy of 99mTc-MIP-1404 SPECT/CT Imaging to Detect Clinically Significant Prostate Cancer in Men With Biopsy Proven Low-Grade Prostate Cancer Who Are Candidates for Active Surveillance (proSPECT-AS)

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: 99mTc-MIP-1404 Injection
* Diagnostic Test: Whole-Body Planar and pelvic SPECT/CT scan


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Ability to provide informed consent and willingness to comply with protocol requirements Life expectancy ≥ 6 months Cohort A only: A diagnostic trans-rectal ultrasound (TRUS)-guided biopsy within 12 months of enrollment showing adenocarcinoma of the prostate gland Within 90 days of consent, serum PSA ≤ 15.0 ng/mL or ≤ 7.5 ng/mL if on 5 α-reductase inhibitors. Candidates for active surveillance and/or a Gleason score ≤3+4 Scheduled to undergo radical prostatectomy (RP) with or without pelvic lymph node dissection (PLND) Cohort B only: Very low risk (VLR) prostate cancer defined by 2016 NCCN Guideline criteria: T1c stage, and PSA < 10 ng/mL, and Gleason score ≤ 6 with < 3 biopsy cores cancer positive and ≤ 50% cancer in any core based on prior prostate biopsy within 24 months of enrollment, and PSA density < 0.15 mg/mL/g Scheduled to undergo a reassessment of prostate cancer staging that includes prostate biopsy as part of routine follow-up EXCLUSION CRITERIA: Subjects administered a radioisotope within 5 physical half-lives prior to study drug injection. Previous treatment with hormonal therapy, surgery (except biopsy), radiation therapy, LHRH analogs, and non-steroidal anti-androgens, for the treatment of prostate cancer or benign prostatic hyperplasia (BPH) Planned androgen or anti-androgen therapy prior to RP surgery or biopsy Subjects with any medical condition or other circumstances that, in the opinion of the investigator, would significantly interfere with obtaining reliable data, achieving study objectives, or completing the study Malignancy (not including curatively treated basal or squamous cell carcinoma of the skin) within the previous 5 years. (Ta stage transitional cell carcinoma bladder cancer with negative surveillance cystoscopy within the past 2 years may be included).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 99mTc-MIP-1404 Injection<br>20 ± 3 millicurie (mCi) intravenous (IV) injection of 99mTc-MIP-1404 | Drug: 99mTc-MIP-1404 Injection<br>* A single dose of 20 (±3) mCi intravenous (IV) injection of 99mTc-MIP-1404.<br>* Other names: 1404;Diagnostic Test: Whole-Body Planar and pelvic SPECT/CT scan<br>* A whole-body planar and pelvic SPECT/CT scan will be obtained 3-6 hours after injection of 99mTc-MIP-1404.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Specificity of 99mTc-MIP-1404 to detect clinically significant prostate cancer when compared to histopathology following either RP [Cohort A] or prostate biopsy [Cohort B] | Tissue distribution of 99mTc-MIP-1404 SPECT/CT imaging in tumor and non-tumorous regions of the prostate and pelvic lymph nodes, if applicable, (as determined by histopathology) in patients undergoing RP (with or without extended pelvic lymph node dissection) or routine prostate biopsy. Pathology results will be used as the truth standard for all imaging analyses. | Within 3-6 hours of dosing, SPECT/CT and whole body planar images will be taken | 
| Sensitivity of 99mTc-MIP-1404 to detect clinically significant prostate cancer when compared to histopathology following either RP [Cohort A] or prostate biopsy [Cohort B] | Tissue distribution of 99mTc-MIP-1404 SPECT/CT imaging in tumor and non-tumorous regions of the prostate and pelvic lymph nodes (as determined by histopathology) in patients undergoing standard of care prostatectomy with or without extended pelvic lymph node dissection. Pathology results will be used as the truth standard for all imaging analyses. | Within 3-6 hours of dosing, SPECT/CT and whole body planar images will be taken | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of 99mTc-MIP-1404 in prostate segments as compared to histopathology following RP [Cohort A only] | Tissue distribution of 99mTc-MIP-1404 SPECT/CT imaging in tumor and non-tumorous regions of the prostate (as determined by histopathology) | Within 3-6 hours of dosing, SPECT/CT and whole body planar images will be taken | 
| Specificity of 99mTc-MIP-1404 in prostate segments as compared to histopathology following RP [Cohort A only] | Tissue distribution of 99mTc-MIP-1404 SPECT/CT imaging in tumor and non-tumorous regions of the prostate (as determined by histopathology) | Within 3-6 hours of dosing, SPECT/CT and whole body planar images will be taken | 
| Clinical safety of 99mTc-MIP-1404 | Clinical laboratory tests will include hematology and clinical chemistry. Vital signs will include heart rate, blood pressure, temperature and respiration rate. | Changes in vital signs and clinical laboratory test results from time of screening until pre-surgery (Day 0 - 42). Treatment-emergent adverse events from study drug injection until pre-surgery or pre-biopsy (within 42 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diagnostic, Active surveillance, Very low risk, Imaging, PSMA, SPECT/CT, 99mTc, Newly Diagnosed, Prostatectomy, Biopsy