PSMA Imaging of Localized Prostate Cancer

Study Overview
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Brief Summary
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The present study is a phase II, open label, single-center, non-randomized, single-dose study. Twenty subjects in total will be enrolled at Weill Cornell Medical College (WCMC)/ NYPH. The primary objective is to evaluate the ability of 89Zr-Df-IAB2M to detect localized, clinically significant (defined as: ≥ 0.5 cm3 with Gleason pattern ≥ 4) prostate cancer (PCa). After the screening period (up to 28 days), each subject will be scheduled to receive 10 mg infusion of IAB2M conjugated with 2.5 mCi 89Zr-Df. 2 - 4 days post-infusion, subjects will undergo a 89Zr-Df-IAB2M PET/CT scan. Images read by a Nuc Med MD reporting: location, SUV and, if possible, size of all areas with abnormal uptake. (they will also undergo a pelvic MRI if they have not obtained an MR image during the screening period or on day of infusion) Optional but recommended 68Ga-PSMA-HBED-CC (5±2mCi) injection and PET/CT scan (1 to 3 hours after the injection) will also be performed prior to radical prostatectomy depending on subject's availability and compliance. Patient will undergo radical prostatectomy after completion of above imaging procedures.

Detailed Description
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The primary endpoint of this study is the proportion of subjects with PSMA-positive (identified by H&E staining and immunohistochemistry) dominant PC lesion(s) greater than 5mm in diameter, whose lesion(s) have been successfully identified by 89Zr-Df-IAB2M imaging. Because this is an exploratory pilot study, no formal sample size/power calculation is required. However, with a sample size of 20 patients in the study, a two-sided 95% confidence interval for the proportion of patients successfully imaged by 89Zr-Df-IAB2M can be constructed to be within ± 19.0% of the observed proportion of patients with successful imaging by 89Zr-Df-IAB2M. This calculation assumes an 89Zr-Df-IAB2M imaging-success proportion of 75%. All estimates from the study will serve as preliminary data (i.e., hypothesis-generating) for future studies.

Official Title
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PSMA Imaging of Localized Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: 89ZR-DF-IAB2M
* Drug: 68Ga-PSMA-HBED-CC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically or cytologically confirmed localized prostate cancer that are scheduled to undergo radical prostatectomy. Age >18 years. Patients must have laboratory values consistent with eligibility to undergo a radical prostatectomy: creatinine less than or equal to 1.5 X upper limit of normal creatinine clearance > 60 mL/min The effects of 89Zr-Df-IAB2M on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while her male partner is participating in this study, she should inform her treating physician immediately. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Treatment or plans for treatment with radiation therapy, surgery, chemotherapy, or investigational therapy between the time of conventional imaging, 89Zr-Df-IAB2M PET/CT and the surgical resection used for the study evaluation. Transrectal prostate biopsy performed less than four weeks prior to 89Zr-Df-IAB2M administration. Uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

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: Interventional<br>Injection of study drug followed by PET/CT imaging. Optional but recommended 68Ga-PSMA-HBED-CC (5±2mCi) injection and PET/CT scan (1 to 3 hours after the injection) will also be performed prior to radical prostatectomy depending on subject's availability and compliance. Followed by prostatectomy | Drug: 89ZR-DF-IAB2M<br>* injection of 10 milligrams of radioactive 89Zr-Df-IAB2M followed by PET/CT scan<br>Drug: 68Ga-PSMA-HBED-CC<br>* Optional but recommended 68Ga-PSMA-HBED-CC (5±2mCi) injection and PET/CT scan (1 to 3 hours after the injection) will also be performed prior to radical prostatectomy depending on subject's availability and compliance.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Subjects With PSMA-positive (Prostate-specific Membrane Antigen) Dominant PC Lesion(s) Greater Than 5mm in Diameter, Whose Lesion(s) Have Been Successfully Identified by 89Zr-df-IAB2M PET/CT | The number of subjects whose lesions have been successfully identified through 89Zr-df-IAB2M PET/CT will be ascertained using a combination of the descriptive statistics and lesion-based analysis, which both utilize multiple measurements | Up to 30 days pre-prostatectomy | 
| The Number of Subjects With PSMA-positive Dominant PC Lesion(s) Greater Than 5mm in Diameter, Whose Lesion(s) Have Been Successfully Identified by 68Ga-PSMA-HBED-CC PET/CT | The number of subjects with PSMA-positive (prostate-specific membrane antigen) dominant PC lesion(s) greater than 5mm in diameter, whose lesion(s) have been successfully identified by 68Ga-PSMA-HBED-CC PET/CT | Up to 30 days pre-prostatectomy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Clinically-significant Lesions Detected by 89Zr-df-IAb2M PET/CT |  | Up to 30 days pre-prostatectomy | 
| The Number of Clinically Significant Lesions Detected by 68Ga-PSMA-HBED-CC PET/CT | Participants underwent 68Ga-PSMA-HBED-CC injection and PET/CT scan (1 to 3 hours after the injection),e performed prior to radical prostatectomy. | Up to 30 days pre-prostatectomy | 
| The Number of Clinically Significant Lesions Detected by mpMRI | pre-prostatectomy standard of care mpMRI used to determine the number of clinically significant lesions | Up to 30 days pre-prostatectomy | 
| The Number of Clinically Significant Lesions Detected by mpMRI in the Subset of Subjects Who Underwent 68Ga-PSMA-HBED-CC PET/CT | The Number of Clinically Significant Lesions Detected by mpMRI in subjects who underwent 68Ga-PSMA-HBED-CC injection and PET/CT | Up to 30 days pre-prostatectomy | 
| The Number of Clinically Significant Lesions Detected by 89Zr-df-IAB2M PET/CT in the Subset of Subjects Who Underwent 68Ga-PSMA-HBED-CC PET/CT | The Number of clinically significant lesions detected by 89Zr-df-IAB2M PET/CT in the subset of subjects who underwent 68Ga-PSMA-HBED-CC Injection and PET/CT | Up to 30 days pre-prostatectomy | 
| The Number of Lesions Involved in Extra-prostatic Extension Identified Through in Vivo 89Zr-df-IAB2M PET/CT |  | Up to 30 days pre-prostatectomy | 
| The Number of Lesions Involved in Extra-prostatic Extension Identified Through 68Ga-PSMA-HBED-CC PET/CT |  | Up to 30 days pre-prostatectomy | 
| The Number of Occult Lymph Nodes Identified by in Vivo 89Zr-df-IAB2M PET/CT |  | Up to 30 days pre-prostatectomy | 
| The Number of Occult Lymph Nodes Identified by in Vivo 68Ga-PSMA-11 PET/CT |  | Up to 30 days pre-prostatectomy | 
| The Number of Observed or Reported Treatment-Emergent Adverse Events Following 89ZR-DF-IAB2M PET/CT (Positron Emission Tomography-Computed Tomography) | All AEs, including unrelated AEs, expected, and unexpected AEs were included in the counts of adverse events | Up to 30 days pre-prostatectomy | 
| The Number of Observed or Reported Treatment-Emergent Adverse Events Following 68Ga-PSMA-HBED-CC PET/CT | All AEs, including unrelated AEs, expected, and unexpected AEs were included in the counts of adverse events | Up to 30 days pre-prostatectomy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PET/CT, Imaging, Nuclear Medicine