GE-148-002: A Phase 2, Open-label, Single-Center Study to Assess GE-148 (18F) Injection PET Imaging to Detect Localized Prostate Cancer

Study Overview
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Brief Summary
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Background: - GE-148 (18F) is a new drug that is designed to attach to prostate cancer cells. Researchers are interested in combining the drug with a small amount of radioactive material to allow prostate cancer lesions to appear more clearly on imaging scans. Researchers are also interested in determining whether the combination can help make cancer cells in pelvic lymph nodes easier to detect through imaging studies. GE-148 (18F) will be used to examine individuals who are scheduled to have surgery on their prostate cancer. Objectives: - To evaluate the effectiveness of GE-148 (18F) in detecting prostate cancer and cancer cells in pelvic lymph nodes using positron emission tomography and magnetic resonance imaging scanning. Eligibility: - Men at least 18 years of age who have been diagnosed with prostate cancer and are scheduled to have prostate removal surgery. Design: Participants will be screened with a physical examination, medical history, blood tests, and imaging studies. Participants will have magnetic resonance imaging (MRI) and positron emission tomography (PET) scans with GE-148 (18F) prior to their scheduled surgery. The MRI and PET scans may be performed on the same day or on different days, depending on the schedule set by the study researchers. Tissue samples taken during prostate removal surgery, including prostate tissue and pelvic lymph nodes, will be collected for further study of the effectiveness of GE-148 (18F).

Detailed Description
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Background: Accurate imaging of prostate cancer is important for developing targeted minimally invasive therapies GE-148 (18F) Injection is a drug product formulation known as [18F]FACBC which is a synthetic leucine amino acid analogue. Preliminary studies demonstrated efficacy in primary prostate cancer and metastatic/recurrent prostate cancers. We propose to evaluate GE-148 (18F) Injection as a PET radiopharmaceutical for the detection of prostate cancer. Objectives: Primary Objective: To differentiate the magnitude of uptake and retention of GE-148 (18F) Injection between malignant prostate tumors, non-malignant prostate pathology, and regions of normal prostate tissue in subjects with prostate cancer. To assess the safety of a single dose of GE-148 (18F) Injection in subjects with prostate cancer. Secondary Objectives: To assess the relationship between the magnitude of uptake of GE-148 (18F) Injection with quantitative assessment of AAT expression in malignant prostate tumors, non-malignant prostate pathology, and regions of normal prostate tissue. To assess the relationship between the magnitude of uptake of GE-148 (18F) Injection with quantitative assessment of Ki-67 expression in malignant prostate tumors, non-malignant prostate pathology, and regions of normal prostate tissue. To assess the relationship between the magnitude of uptake of GE-148 (18F) Injection in malignant prostate tumors and their Gleason Score. To assess the ability of GE-148 (18F) Injection to detect the number of discrete malignant prostate tumors confirmed by histopathology. To assess the relationship between the magnitude of uptake of GE-148 (18F) Injection with quantitative measurement of AAT and Ki-67 expression in pelvic lymph nodes showing uptake of GE-148 (18F) Injection, where available. To compare the ability of PET/CT imaging with GE-148 (18F) Injection to predict prostate malignancy and distinguish it from other pathologies (inflammation, hyperplasia, atrophy, hemorrhage) with that of T2W MRI, DCE MRI, MR DWI, and MRSI performed at 3T. Eligibility: Subject is 18 years old, ECOG 0-2, with documented prostate cancer (minimum 1 core). Subject must be scheduled to undergo standard of care prostatectomy at NIH CC Serum creatinine within 2 weeks prior to MRI less than or equal to1.8mg/dl, estimated GFR(eGFR) must be greater than 30 ml/min/1.73m2. -Chemistry parameters: Aspartate aminotransferase (AST), Alanine transferase (ALT)2 x of the upper limits of normal; total bilirubin, of less than 2 x the upper limits of normal or less than 3.0 mg/dl in patients with Gilbert's syndrome. Design: Thirty subjects with localized prostate cancer scheduled for prostatectomy will undergo dynamic GE-148 (18F) Injection PET/CT imaging, and undergo a standard-of-care endorectal coil/pelvic multiparametric MRI . Results will be compared with pathology.

Official Title
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GE148-002: A Phase 2, Open-label, Single-Center, Study to Assess GE-148 (18F) Injection Positron Emission Tomography(PET) Imaging to Detect Localized Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: GE-148 (18F)


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Subject is male and is greater than or equal to 18 years old. Subject must be scheduled to undergo standard of care prostatectomy for presumed localized prostate cancer at the NIH Clinical Center. Recent (within 12 months of study entry but not within 8-12 weeks before start of imaging study) prostate biopsy indicating the presence of adenocarcinoma of the prostate gland in which at least sextant biopsies were obtained. Subjects must have a minimum of 1 positive-for-cancer biopsy core. Serum creatinine within 2 weeks prior to MR imaging less than or equal to 1.8 mg/dl and eGFR must be greater than 30 ml/min/1.73m(2) Chemistry parameters: AST and ALT 2 x of the upper limits of normal; total bilirubin, of less than or equal to 2 x the upper limits of normal or less than 3.0 mg/dl in patients with Gilbert's syndrome. Eastern Cooperative Oncology Group (ECOG) Performance score of 0 to 2. Ability to provide informed consent. All subjects must sign an informed consent form indicating their understanding of the investigational nature and risks of the study before any protocol-related studies are performed. The subject has a clinically acceptable medical history, physical examination and vital signs findings during the screening period (from within 21 days before administration of GE-148 (18F) Injection). EXCLUSION CRITERIA: Known allergy to gadolinium. Subjects for whom participating would significantly delay the scheduled standard of care therapy. Subjects with any coexisting medical or psychiatric condition that is likely to interfere with study procedures and/or results. Subjects with severe claustrophobia unresponsive to oral anxiolytics. Subjects with contraindications to MRI Subjects weighing more than 136 kg (weight limit for scanner table). Subjects with pacemakers, cerebral aneurysm clips, shrapnel injury, or other implanted electronic devices or metal not compatible with MRI. Subjects with contraindication to endorectal coil placement Severe hemorrhoids. Surgically absent rectum. Other medical conditions deemed by the principle investigator (or associates) or sponsor to make the subject ineligible for protocol procedures. Subjects who have previously received radiation therapy to the pelvis. Subjects who have received androgen-deprivation therapy. The subject has received, or is scheduled to receive, another IMP from 1 month before to 1 week after administration of GE-148 (18F) Injection. Subjects with chronic renal failure (eGFR less than 30 ml/min/1.73m(2)).

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GE 148-002<br> | Drug: GE-148 (18F)<br>* All subjects will receive an i.v. dose of GE-148 (18F) Injection at 10 mCi (370 MBq) to provide adequate image quality throughout the specified imaging period.<br>* Other names: GE-148 (18F) Injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Assess the Magnitude of Uptake and Retention of GE-148 (18F) Injection in Malignant Prostate Tumors, Non-malignant Prostate Pathology, and Regions of Normal Prostate Tissue in Subjects With Prostate Cancer, Using PET/CT Imaging. | Quantitative measurements of the level of uptake of GE-148 (18F) Injection into each tissue type (malignant prostate tumors, non-malignant prostate pathology, and regions of normal prostate) calculated as Standardized Uptake Values (SUVs), using histopathology as the standard of truth. | After GE-148 (18F) Injection administration. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Compare the Ability of PET/CT Imaging With GE-148 (18F) Injection to Predict Prostate Malignancy and Distinguish it From Other Pathologies (Inflammation, Hyperplasia, Atrophy, Hemorrhage) With That of T2W MRI, DCE MRI, MR DWI, and MRSI Performed at 3T. | Use of descriptive statistics to compare the ability of the PET/CT imaging and MRI to predict malignancy, based on histopathology as the standard of truth, on a subject basis and per lesion basis. | After GE-148 (18F) Injection administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate Cancer, MRI, PET, GE-148 (18F)