Expanded Access to Diagnostic Imaging for Staging of Recurrent Prostate Cancer

Expanded Access to 11C Choline PET/CT and 11C Choline PET/MR for Staging of Recurrent Prostate Cancer With Comparison Study of CT and MR Modalities

This Phase 3 study will target approximately 100 men over age 18 who have a biochemical relapse or other evidence of relapse of prostate cancer after primary treatment. The purpose of this study is to: A. Provide expanded access the drug 11C-choline. B. Determine the performance characteristics (sensitivity, specificity, positive predictive value, negative predictive value) of 11C-choline PET/Computed Tomography (CT) and PET/Magnetic Resonance Imaging (MRI) in the detection of metastatic prostate cancer in patients with biochemical relapse of prostate cancer after primary treatment in a prospective manner. C. Determine the optimal Prostate-Specific Antigen (PSA) trigger value in 11C-choline PET/CT and PET/MRI positive patients through a prospective study. D. Determine factors that predict a confirmed positive 11C-choline PET/CT and PET/MRI using a multivariable analysis of clinical and pathologic data collected prospectively. E. Compare the individual performance characteristics of 11C-choline PET/CT and 11C-choline PET/MRI and the combination of 11C-choline PET/CT and PET/MRI Study Protocol: Patients entered into the study will undergo a 11C-choline PET CT scan and MRI scan. The CT and MRI images will be evaluated for evidence of metastatic prostate cancer. The 11C-choline PET CT and MRI images will be evaluated for evidence of metastatic prostate cancer. Evidence of metastasis on conventional imaging or 11C-choline PET will be confirmed with biopsy or surgical pathology when possible, or by response to treatment on subsequent imaging. Rates of confirmed metastasis between conventional CT and MRI images will be compared with the 11C-choline PET CT and MRI images. Upon conclusion of each imaging protocol, the referring physician will receive written documentation of the results. At this time, the patient will be considered off study and no further follow up is required.

The first arm of this study serves to provide expanded access to 11C-choline injection as currently defined under the reference listed drug label as an investigational drug in geographical service areas where 11C-choline is not available. The second arm expands access as well but also attempts to determine the more effective imaging modality and conditions between PET/CT and PET/MR. The study will consist of patients who have a biochemical relapse or other evidence of relapse after primary treatment. The first arm of the study is open to as many patients who elect to participate in the study that are over the age of 18 and have experienced a biochemical relapse of prostate cancer after primary treatment. The second arm will consist of patients who have been treated with radiation therapy, or androgen suppression and radiation therapy who have a PSA > 2 ng/mL higher than the nadir level. The nadir level in patients who have been treated with androgen suppression and radiation therapy is determined after the serum testosterone level has normalized. This study group will also consist of patients who have been treated with radical prostatectomy and who have a biochemical relapse defined as a PSA of 0.2 ng/mL confirmed at that level or higher on a subsequent PSA test 3 months later. This group may consist of men who have other clinical evidence of relapse such as a suspicious bone scan or CT scan regardless of PSA kinetics. Patients identified as potential subjects will be screened against the eligibility criteria as defined above in Section 5.1. Informed consent will be obtained from all participants before any study related procedures are conducted. Each participant will be informed about the nature of the study, its purpose, and possible risks. Informed consent will be documented by using the written informed consent document approved by the local IRB at the Decatur Memorial Hospital. At the time of referral, patients will be asked to bring their prior records as it pertains to their prostate cancer history. Data collected from outside records, such as radiographic studies, previous imaging studies and biopsies will be incorporated into the study record. Abstracted data for the study record will include: Patient demographics such as age, race, and family history of prostate cancer Risk factors such as finasteride or dutasteride use, and environmental exposure (eg. Agent orange) Prostate exam results, most recent within last 90 days PSA test results, most current and past Past medical and surgical history Current medications Allergies Pathology reports Imaging reports Date of diagnosis Date(s) of biochemical relapse and coordinating PSA results. Once all records have been assessed for eligibility, an order for the 11C-choline PET CT scan and MRI scan will be requested from the referring physician and patient will be scheduled and given the appropriate prep instructions. Both arms of the study will undergo a 11C-choline PET CT scan and MRI scan. The CT scan will be performed with intravenous contrast unless deemed unsafe by lab values. The CT and MRI images will be evaluated for evidence of metastatic prostate cancer. The 11C-choline PET CT and MRI images will be evaluated for evidence of metastatic prostate cancer. Unequivocal evidence of metastasis on both conventional imaging and 11C-choline PET will be considered a true positive. Evidence of metastasis on conventional imaging or 11C-choline PET will be confirmed with biopsy or surgical pathology when possible, or by response to treatment on subsequent imaging. If confirmation of metastasis is not achievable by biopsy or surgical pathology, then confirmation will be achieved with 11C-choline PET CT and MRI images obtained 3 months after treatment conclusion. Rates of confirmed metastasis between conventional CT and MRI images will be compared with the 11C-choline PET CT and MRI images. Upon conclusion of each imaging protocol, the referring physician will receive written documentation of the results. At this time, the patient will be considered off study and no further follow up is required.

The key objective of this study is to provide expanded access to this drug product as currently defined under the reference listed drug as an investigational drug in geographical service areas where 11C-choline injection is not available. Patients entered into the study will undergo a 11C-choline PET CT scan and MRI scan. The 11C-choline PET CT and MRI images will be evaluated for evidence of metastatic prostate cancer. Patient data obtained in this arm of the study will not be further analyzed beyond that need for clinical diagnosis.

11C-choline injection is approved for use in conjunction with both CT and MR imaging modalities. This arm will attempt to determine which modality is most efficacious and under which conditions. Patients entered into the study will undergo imaging using GE's Trimodality Imaging System that combines PET, CT, and MR techniques to provide PET/CT and PET/MR fused images

Choline C11 Injection for PET/CT Imaging Protocol: 15 - millicuries (mCi) 11C-choline IV Injection PET images skull base to mid thigh with 3 min per bed position Use of IV contrast based on American College of Radiology (ACR) IV contrast guidelines for a renal function screening protocol Fusion of PET and CT images Choline C11 Injection for PET/MRI Whole Body Imaging Protocol: No IV contrast High resolution axial T2 prostate bed, axial Diffusion Weighted Image (DWI) pelvis, coronal T2 skull base to mid thighs Fusion of coronal and PET images

The CT and MRI images will be evaluated for evidence of metastatic prostate cancer. This Outcome is only measured for Arm 2 of this study. True Positive: True positives will consist of evidence of metastatic prostate cancer on conventional CT or MRI images or on 11C-choline PET/CT or MRI images confirmed with biopsy, surgical pathology, or by response to treatment with androgen suppression or other medical or radiation therapy. True Negative: True negatives will consist of negative images. False Positive: False positive will consist of evidence of metastatic prostate cancer on conventional CT or MRI images or on 11C-choline PET/CT or MRI images, but without corresponding confirmation from biopsy, surgical pathology or response to treatment. False Negative: False negative will consist of negative images, but with positive biopsy, surgical pathology or a response to treatment.

After 11C-choline PET CT scan and MRI scans, approximately 1 day. If surgery or response to treatment required to evaluate, approximately 1 to 3 months.

The results of the population's 11C-choline PET CT scans and MRI scans will be evaluated for imaging sensitivity. Sensitivity of 11C-choline PET/CT and MRI will be calculated as True Positive / (True Positive + False Negative). This Outcome is only measured for Arm 2 of this study.

The results of the population's 11C-choline PET CT scans and MRI scans will be evaluated for imaging specificity. Specificity of 11C-choline PET/CT and MRI will be calculated as True Negative / (True Negative + False Positive). This Outcome is only measured and reported for Arm 2.

The results of the population's 11C-choline PET CT scans and MRI scans will be evaluated for the images' positive predictive value. Positive Predictive Value of 11C-choline PET/CT and MRI will be calculated as True Positive / (True Positive + False Positive). This Outcome is only measured for Arm 2.

The results of the population's 11C-choline PET CT scans and MRI scans will be evaluated for the images' negative predictive value. Negative Predictive Value of 11C-choline PET/CT and MRI will be calculated as True Negative / (True Negative + False Negative). This Outcome is only measured for Arm 2.

Count of Participants With Positive or Negative PET, CT, or MRI Modalities Resulting in Prostate Cancer (PCa) Confirmation

Comparison of the results of participants' imaging modalities and whether those imaging modalities resulted in confirmation of Prostate Cancer (PCa). This Outcome is only measured for Arm 2.

The participants' age at primary treatment was collected upon study enrollment (approximately 1 week into study)

The Prostate-Specific Antigen (PSA) measurement of participants at their original prostate cancer diagnosis was collected at entry to this trial. It is reported as nanograms of PSA per milliliter (ng/mL) of blood. The Median of all reported PSAs is reported here.

The participants' primary PSA at diagnosis was collected upon study enrollment (approximately 1 week into study)

An accounting of the approximate clinical (pre-treatment) stage for the Arm 2 participants. Clinical staging is based on the results of tests done before surgery. T1: PC is too small to be seen on a scan or felt during prostate examination T1a: PC is in < 5% of removed tissue T1b: PC is in > 5% or more of removed tissue T1c: PC is found by biopsy T2: PC is completely inside prostate T2a: PC is in only half of one side of prostate T2b: PC is in more than half of one side of prostate, but not both sides T2c: PC is in both sides but is still inside prostate T3: PC has broken through the capsule of prostate T3a: PC has broken through the capsule of prostate T3b: PC has spread into seminal vesicles T4: PC has spread into other nearby body organs

The participants' clinical stage data was collected upon study enrollment (approximately 1 week into study)

The median primary Biopsy Gleason Score for the Arm 2 participants' will be reported. The Gleason Score is the grading system used to determine the aggressiveness of prostate cancer. Typical Gleason Scores range from 6-10. The higher the Gleason Score, the more likely that the cancer will grow and spread quickly. Gleason scores 2-4 are typically found in smaller tumors located in the transitional zone (around the urethra). The majority of treatable/treated cancers are of Gleason scores 5 - 7 and are detected due to biopsy after abnormal digital rectal exam or prostate specific antigen evaluation. The cancer is typically located in the peripheral zone usually the posterior portion. Tumors with Gleason scores 8-10 tend to be advanced neoplasms that are unlikely to be cured.

The participants' primary Biopsy Gleason Score data was collected upon study enrollment (approximately 1 week into study)

An accounting of the primary treatment modalities undergone by the participants in Arm 2 prior to their involvement in the trial will be reported. Modalities reported below are: Androgen Deprivation Therapy (ADT) External Beam Radiation Therapy (EBRT) Brachytherapy Cryoablation Cystoprostatectomy Intensity-Modulated Radiation Therapy (IMRT) Radical Prostatectomy (RP)

The participants' primary treatment data was collected upon study enrollment (approximately 1 week into study)

The pathological stage of PC at primary diagnosis for Arm 2 participants was collected. pT is based on how different from normal the cells in samples of tissue recovered from surgery look under a microscope. T1: PC is too small to be seen on a scan or felt during prostate examination T1a: PC is in < 5% of removed tissue T1b: PC is in > 5% or more of removed tissue T1c: PC is found by biopsy T2: PC is completely inside prostate T2a: PC is in only half of one side of prostate T2b: PC is in more than half of one side of prostate, but not both sides T2c: PC is in both sides but is still inside prostate T3: PC has broken through the capsule of prostate T3a: PC has broken through the capsule of prostate T3b: PC has spread into seminal vesicles T4: PC has spread into other nearby body organs

The participants' primary pathological staging data was collected upon study enrollment (approximately 1 week into study)

A census of the primary surgical margins of participants in Arm 2 will reported. The surgical margins are the set of surfaces that were cut by the surgeon in order to remove the specimen from the body. Positive Margin: surgical margins with disease present. Negative Margin: surgical margins with no disease present.

The participants' primary surgical margins data was collected upon study enrollment (approximately 1 week into study)

A census of the positive lymph node ratio, defined as ratio of positive lymph nodes to all lymph nodes removed, for the participants of Arm 2 will be reported. The N refers to the the number of nearby lymph nodes that have cancer. NX: Cancer in nearby lymph nodes cannot be measured. N0: There is no cancer in nearby lymph nodes. N1, N2, N3: Refers to the number and location of lymph nodes that contain cancer. The higher the number after the N, the more lymph nodes that contain cancer.

The participants' primary positive lymph note ratio was collected upon study enrollment (approximately 1 week into study)

A census of the additional treatments undergone by participants prior to enrollment in the study, if undergone, for the participants of Arm 2 will be reported. None Androgen Deprivation Therapy (ADT) Radiation Therapy (RT) Electron Beam Radiation Therapy (EBRT) Lycopene (herbal treatment) Salvage Radiation Therapy (RT) Salvage Radical Prostatectomy (RP) Adjuvant Radiation Therapy (RT) Bilateral Pelvis Lymph Node Dissection

The participants' additional primary treatment data was collected upon study enrollment (approximately 1 week into study)

The median of the Arm 2 participants' data between initial treatment and biochemical relapse, occurring prior to study enrollment, measured in months, will be reported.

The participants' biochemical relapse data was collected upon study enrollment (approximately 1 week into study)

The participants' age at study entry was collected upon study enrollment (approximately 1 week into study)

The median of the PSA of Arm 2 participants at study entry will be reported as nanograms of PSA per milliliter (ng/mL) of blood

The median of the time, measured in months that an Arm 2 participant's PSA has doubled from initial diagnosis to PSA measured at study enrollment.

The participants' PSA doubling time was collected upon study enrollment (approximately 1 week into study)

An accounting of whether the participants of Arm 2 have undergone androgen deprivation therapy (ADT).

The participants' participation in ADT was collected upon study enrollment (approximately 1 week into study)

Inclusion Criteria: For biochemical relapse after primary treatment PSA > 0.2 ng/ml after radical prostatectomy confirmed at that level or higher on a subsequent test 3 months later PSA increase >2 ng/ml from nadir following radiation therapy PSA increase >2 ng/ml from nadir following radiation therapy plus androgen deprivation therapy with nadir defined with normalized testosterone level Two consecutive PSA increases from nadir level after androgen blockade or androgen suppression therapy Kidney function with GFR > 60 mL/sec/1.73m2 and Creatinine < 1.7mg, collected within 90 days of planned scan if GFR is > or equal to 60 mL/sec/1.73m2, PET/CT will be completed with contrast if GFR is < 60 mL/sec/1.73m2, PET/CT will be completed without contrast if Creatinine is > than 1.7 mg, Radiology will follow ACR recommendations as outlined in department policy. No known allergy to iodinated radiologic contrast media Able to have MRI based on screening evaluation. If patient is found to be MRI incompatible, the 11C-choline PET/MRI portion of the study will not be completed. Please see the provided contact numbers for further options. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 Exclusion Criteria: ECOG Performance Status > 2. Concurrent malignancy, i.e. colon cancer. Treatment for another malignancy except superficial skin cancer within 5 years