18F-DCFBC PET/CT in Prostate Cancer

Study Overview
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Brief Summary
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Background: - Prostate cancer is the second leading cause of cancer deaths in American men. A chemical called a radiotracer helps doctors get images of this type of cancer. Researchers want to test a radiotracer called N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-(18)F-fluorobenzyl-L-cysteine ((18)F-DCFBC) (18F-DCFBC). Objective: - To see if the radiotracer 18F-DCFBC can identify sites of prostate cancer in the body. Eligibility: - Men ages 18 and over with prostate cancer. The cancer must be newly diagnosed, have relapsed, or has spread outside the prostate. Design: Participants will be screened with physical exam and medical history. They will give a blood sample. Participants will be divided into three groups. Group 1: people with cancer only in the prostate scheduled for surgical prostate removal or biopsy at National Institutes of Health (NIH). Group 2: people who had their prostate removed or had radiation therapy and now have a rising prostate-specific antigen (PSA) without other signs of disease. Group 3: people whose cancer has spread to other areas of the body. Participants will have 18F-DCFBC injected into a vein then imaged in a positron emission tomography (PET)/computed tomography (CT) camera. During the scans, they will lie on their back on the scanner table. Group 1 will have a magnetic resonance imaging (MRI) scan. A tube will be placed in the rectum. Coils may be wrapped around the outside of the pelvis. Participants will have a contrast agent injected through an intravenous line. Group 3 will have another PET/CT scan with a different radiotracer, 18F NaF, within 21 days of the 18F-DCFBC scan to look for prostate cancer in the bone. Group 3 will repeat the two PET/CT scans 4-6 months after the initial scans. A few days after each scan, participants will be contacted for follow-up.

Detailed Description
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Background Prostate cancer is the second leading cause of cancer deaths in American men. Current methods of imaging advanced prostate cancer (computed tomography ((CT) and bone scan) are non specific and new, more specific molecular imaging probes are sought. Many prostate cancers express the prostate specific membrane antigen (PSMA) a transmembrane protein with N-acetylated alpha-linked acidic dipeptidase (NAALADase) enzymatic activity. PSMA is also expressed in angiogenesis but otherwise has limited expression in normal tissue. N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-(18)F-fluorobenzyl-L-cysteine ((18)F-DCFBC) (18F-DCFBC) is a radiolabeled positron emission tomography (PET) agent which binds with high affinity to PSMA and through whole-body non-invasive functional imaging, may provide new information on the expression of PSMA. Primary Objective - To assess the ability of 18F-DCFBC to differentiate between tumorous and nontumorous tissues in localized, recurrent (based on rising prostatic-specific antigen ((PSA) post treatment) and metastatic prostate cancer Eligibility Subject is greater than or equal to 18 years old Eastern Cooperative Oncology Group (ECOG) 0-2 with adenocarcinoma of the prostate and fits criteria for one of the following: ARM 1 -- Patients with known localized prostate cancer with a soft tissue lesion at least 6mm or greater. ---A multiparametric magnetic resonance imaging (MRI) (standard of care at the National Institutes of Health ((NIH) Clinical Center) must be performed within 4 months of18F-DCFBC injection with findings suggestive for prostate cancer and confirmed with histopathology. ARM 2 Patients with biochemical prostate cancer relapse after definitive treatment For patients status post radiation therapy for prostate cancer, a PSA increase from post radiation therapy nadir OR For patients status post prostatectomy, any PSA >/=0.2 ng/ml Nonspecific or no evidence for disease on standard imaging modality ARM 3 Patients with identifiable metastatic disease on a conventional imaging modality. If only soft tissue metastasis, one lesion must measure 6mm or greater. Patients must have confirmation of prostate cancer prior to 18F-DCFBC imaging. Design This is a single site 3-arm study enrolling a total of 110 evaluable patients: Arm 1 will include 12 patients with presumed localized prostate cancer scheduled to undergo prostatectomy or biopsy within 4 months of enrollment; Arm 2 will include 78 patients with biochemical recurrence without evidence of metastasis on conventional imaging; and Arm 3 will include 20 patients with known metastatic disease who may or may not be on or/scheduled to begin therapeutic intervention. Patients with presumed localized disease will undergo a standard of care, clinical multiparametric endorectal coil MRI in the National Cancer Institute (NCI) Molecular Imaging Clinic within 4 months of screening. Patients in Arm 3 will undergo 2 imaging sessions: baseline and 4-6 month follow-up. Clinical records (including PSA) and treatment (if any) that occurred in the imaging interval must be available. All patients in Arm 3 will also undergo Na18F PET/CT for evaluation of bone metastases as part of this protocol. In order to allow for a small number of nonevaluable patients, the accrual ceiling will be set at 125.

Official Title
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A Pilot Study of 18F-DCFBC PET/CT in Prostate Cancer

Conditions
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Prostatic Neoplasms, Prostate Cancer

Intervention / Treatment
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* Drug: 18F DCFBC
* Drug: Sodium (Na)18F positron emission tomography (PET)/computed tomography (CT)


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Subject is greater than or equal to18 years old Platelet count > 50,000/mm^3 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. Categories ARM 1 only ---For patients with presumed localized disease (any tumor (T), nodes 0 (N0), metastasized 0 (M0)), a multiparametric magnetic resonance imaging (MRI) (standard of care at the National Institutes of Health ((NIH) Clinical Center) must be performed within 4 months of the N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-(18)F-fluorobenzyl-L-cysteine ((18)F-DCFBC) (18F-DCFBC) injection with findings suggestive for prostate cancer and a prostate lesion at least 6mm or greater. Must have histopathologic confirmation of prostate cancer prior to 18F-DCFBC imaging. ARM 2 only: For patients status post radiation therapy for prostate cancer, any prostatic-specific antigen (PSA) increase from post radiation therapy nadir OR For patients status post prostatectomy, a PSA >/=0.2 ng/ml Nonspecific or no evidence for disease on standard imaging modality ARM 3 only: Patients must have identifiable metastatic disease on at least 1 clinically indicated imaging modality. If only soft tissue metastasis, one lesion must measure at least 6mm or greater. Patients must have confirmation of prostate cancer prior to 18FDCFBC imaging Note: A patient who is eligible for one arm, subsequently may cross-over into a different arm. EXCLUSION CRITERIA: 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 Other medical conditions deemed by the principal investigator (or associates) to make the subject unsafe/ineligible for protocol procedures. Subjects weighing > 350 lbs. (weight limit for scanner table), or unable to fit within the imaging gantry Serum creatinine > 2 times the upper limit of normal Total bilirubin > 2 times the upper limit of normal Liver transaminases (alanine aminotransferase (ALT), aspartate aminotransferase (AST)) greater than 3 times the upper limit of normal

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Suspected Localized Prostate Cancer<br>Patients with known localized prostate cancer with a soft tissue lesion at least 6mm or greater. | Drug: 18F DCFBC<br>* Each subject will receive a single intravenous (i.v.) dose of 18F DCFBC by bolus injection at a rate of approximately 1 ml/3-5 sec.<br>|
| Experimental: Biochemical Recurrence<br>Patients with biochemical prostate cancer relapse after definitive treatment | Drug: 18F DCFBC<br>* Each subject will receive a single intravenous (i.v.) dose of 18F DCFBC by bolus injection at a rate of approximately 1 ml/3-5 sec.<br>|
| Experimental: Known Metastatic Disease<br>Patients with identifiable metastatic disease on a conventional imaging modality. If only soft tissue metastasis, one lesion must measure 6mm or greater. Patients must have confirmation of prostate cancer prior to investigational imaging. | Drug: 18F DCFBC<br>* Each subject will receive a single intravenous (i.v.) dose of 18F DCFBC by bolus injection at a rate of approximately 1 ml/3-5 sec.<br>Drug: Sodium (Na)18F positron emission tomography (PET)/computed tomography (CT)<br> <br> * Other names: Na 18F PET/CT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Local Recurrence, Lymph Node Metastases or Distant Metastatic Sites Detected by N-[N-[(S)-1,3-dicarboxypropyl]Carbamoyl]-4-(18)F-fluorobenzyl-L-cysteine ((18)F-DCFBC) Imaging | Any abnormal focus of 18F-DCFBC uptake higher than the surrounding background and not associated with physiological uptake was considered positive for prostate cancer, and each was classified as local recurrence, lymph node metastases or distant metastatic sites. | 1 hour and 2 hour timepoints at baseline | 
| Number of Lesions Detected by N-[N-[(S)-1,3-dicarboxypropyl]Carbamoyl]-4-(18)F-fluorobenzyl-L-cysteine ((18)F-DCFBC) | Any abnormal focus of 18F-DCFBC uptake higher than the surrounding background and not associated with physiological uptake was considered a positive lesion for prostate cancer.The measure would be compared with other imaging or pathology. | 1 hour and 2 hour timepoints at baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) | Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. | Date treatment consent signed to date off study, approximately 42 months and 21 days | 
| Number of Detectable Lesions in Bone With Respect to 18F-DCFBC Imaging and/or Na18F Positron Emission Tomography (PET)/Computed Tomography (CT) in Patients With Known Metastatic Disease | 18F-DFBC and conventional imaging was used to identify positive lesions in bone. | 3 months | 
| Average Standardized Uptake Value (SUVmax) for Primary Prostate Cancer Patients Compared to Benign Prostatic Hyperplasia (BPH) | Primary prostate cancer was compared to BPH nodules and normal prostate tissue using a one-way analysis of variance (Anova). Negative uptake is defined as tumor uptake less than adjacent background soft tissue, or blood pool for lymph nodes. | 1 hour and 2 hour post injection (p.i.) | 
| Median Tumor Foci Size in Suspected Localized Prostate Cancer Patients Undergoing Prostatectomy | Tissue was obtained and stained with hematoxylin-eosin. The resulting whole mount specimens were correlated with MRI and PET/CT imaging. For each dominant/index tumor (largest tumor with highest Gleason score) was determined. | 1 month | 
| Detectability of Suspicious Prostate Cancer Lesions in Suspected Localized Prostate Cancer Patients With Prostate Gland | Visualizing positive lesions with DCFBC and mpMRI. | 3 months | 
| Detectability of Suspicious Tumors Based on Prostate Specific-Antigen (PSA) Levels in the Biochemical Recurrence Group | Visualizing positive lesions as a function of PSA value. Undetectable PSA is normal in this population. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Imaging, NaF, Prostate Specific Membrane Antigen, Radiolabeled PET Agent