18F-DCFBC PET/CT in Prostate Cancer

Early Phase 1

Completed

Conditions: Prostatic Neoplasms
Prostate Cancer

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

Registration Number: NCT02190279

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 116

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Known Metastatic Disease	Sodium (Na)18F positron emission tomography (PET)/computed tomography (CT)	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.
Known Metastatic Disease	18F DCFBC	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.
Suspected Localized Prostate Cancer	18F DCFBC	Patients with known localized prostate cancer with a soft tissue lesion at least 6mm or greater.
Biochemical Recurrence	18F DCFBC	Patients with biochemical prostate cancer relapse after definitive treatment

Primary Outcome Measures

Name	Time	Method
Number of Lesions Detected by N-[N-[(S)-1,3-dicarboxypropyl]Carbamoyl]-4-(18)F-fluorobenzyl-L-cysteine ((18)F-DCFBC)	1 hour and 2 hour timepoints at baseline	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.
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	1 hour and 2 hour timepoints at baseline	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.

Secondary Outcome Measures

Name	Time	Method
Median Tumor Foci Size in Suspected Localized Prostate Cancer Patients Undergoing Prostatectomy	1 month	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.
Detectability of Suspicious Prostate Cancer Lesions in Suspected Localized Prostate Cancer Patients With Prostate Gland	3 months	Visualizing positive lesions with DCFBC and mpMRI.
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	3 months	18F-DFBC and conventional imaging was used to identify positive lesions in bone.
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)	Date treatment consent signed to date off study, approximately 42 months and 21 days	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.
Average Standardized Uptake Value (SUVmax) for Primary Prostate Cancer Patients Compared to Benign Prostatic Hyperplasia (BPH)	1 hour and 2 hour post injection (p.i.)	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.
Detectability of Suspicious Tumors Based on Prostate Specific-Antigen (PSA) Levels in the Biochemical Recurrence Group	3 months	Visualizing positive lesions as a function of PSA value. Undetectable PSA is normal in this population.