Prostate Specific Membrane Antigen (PSMA)-Based PET Imaging of High Risk Prostate Cancer
Prostate Specific Membrane Antigen (PSMA)-Based PET Imaging of High Risk Prostate Cancer
Background:

 People with prostate cancer usually have their cancer imaged with a CT scan and bone scan.
 They then have their prostate gland removed. Researchers want to test a scan that might
 predict if prostate cancer will return after this surgery.

 Objective:

 To test if a PET/CT scan before the prostate gland is removed can predict if prostate cancer
 will return. Also, to test if this approach is better or worse than the usual approach for
 prostate cancer.

 Eligibility:

 Men ages 18 and older with prostate cancer that appears to be contained within the prostate
 but is at risk of having spread

 Design:

 Participants will be screened with:

 -  Medical history

 -  Blood tests

 -  CT and MRI scans: Participants will lie in a machine. The machine will take pictures of
 the body.

 -  Bone scan

 Participants will have a radiotracer injected into a vein. They will have a PET/CT scan of
 their whole body 60 90 minutes later. During the scan, they will lie on their back and stay
 still.

 Within 60 days after the scan, participants will have surgery. This will remove the prostate
 gland and lymph nodes around it. Some tissue will be used for genetic testing.

 If the PET/CT scan suggests the cancer has spread, participants may need to have another
 biopsy within 60 days after the scan.

 After surgery, participants will have follow-up visits for 5 years. They will have 5 visits
 the first year and 2 the second. Then they will have visits once a year.

 If participants cancer returns, they will have repeat PET/CT scans.
Background:

 -  About 30,000 men will die from prostate cancer in the US in 2018. The majority of these
 men originally presented with localized cancer.

 -  Treatment options for patients with high risk, localized disease typically involve
 radical prostatectomy (RP) or radiation therapy (RT) in combination with androgen
 deprivation therapy (ADT). Following RP, 70% of patients with high-risk disease will
 experience a biochemical recurrence at 5 years, and approximately 20% will die of their
 disease in 10-15 years, likely due to metastatic disease that was not detectable using
 conventional imaging (99mTc-methylene diphosphonate bone scan and X-ray computed
 tomography) at

 the time of prostatectomy.

 -  Prostate-specific membrane antigen (PSMA) is commonly expressed in prostate cancers and
 is associated with biologic aggressiveness.

 -  The second generation, PET tracer 18F-DCFPyl binds to the enzymatic portion of PSMA. It
 exhibits high uptake in tumor and rapid washout in normal tissues leading to high tumor
 to background ratios and the possibility of detecting metastases when conventional
 imaging is negative.

 Objective:

 -To determine if patients with a preoperative 18F-DCFPyL PET/CT that is negative for
 metastases experience 5 year progression free survival (PFS) which is improved (40%) over
 that of historical data (30%) based on a general population of similar patients who have not
 undergone imaging with 18F-DCFPyL PET/CT

 Eligibility:

 -  Men greater than or equal to 18 years of age at the time of providing informed consent.

 -  Patients must have histologically proven prostate adenocarcinoma confirmed by a CLIA
 certified laboratory

 -  Eastern Cooperative Oncology Group (ECOG) performance status: less than or equal to 2.

 -  Must have prostate cancer with high risk features defined as:

 -  Gleason 8 and higher OR

 -  PSA > 20 ng/mL OR

 -  Clinical stage T3a (i.e. likely extraprostatic extension on MRI) or T3b

 -  Laboratory parameters:

 -  Hemoglobin >= 9 g/dL

 -  Leukocytes >=3,000/mcL

 -  Platelets >=100,000/mcL

 -  Total bilirubin <2 X normal institutional limits

 -  AST(SGOT)/ALT(SGPT) less than or equal to 3 X normal institutional limits

 -  Creatinine <2 X normal institutional limits OR

 -  eGFR >=50 mL/min/1.73 m2 for patients with creatinine levels above institutional
 normal (calculated via the MDRD equation)

 -  Patients must be planning to undergo radical prostatectomy and lymphadenectomy
 regardless of findings on 18F-DCFPyL PET/CT.

 -  Willingness and ability to undergo multiparametric prostate MRI and 18F-DCFPyL PET/CT

 Design:

 -  This is an open-label, non-randomized, multi-center trial designed to evaluate the
 impact of 18F-DCFPyL PET/CT imaging on Progression-Free Survival at 5 years in patients
 with high risk localized prostate cancer.

 -  All subjects meeting eligibility criteria will undergo baseline assessments to include
 multiparametric MRI of the prostate, 99mTc-methylene diphosphonate bone scan and
 contrast-enhanced CT of the abdomen and pelvis.

 -  All subjects meeting eligibility criteria will undergo 18F-DCFPyL PET/CT.

 -  The study will enroll up to 200 patients from 7 centers. Up to 40 patients will be
 enrolled at NCI.

 -  All subjects will undergo radical prostatectomy and lymphadenectomy within 60 days
 following PET/CT imaging.

 -  Subjects will be evaluated at 6 weeks, at 3, 6, 9, 12, and 18 months, at 2, 3, 4, and 5
 years post-prostatectomy to determine if there has been progression and to record
 details of subsequent treatment and response.

 -  18F-DCFPyL PET/CT imaging will be repeated at the time of progression.
-  INCLUSION CRITERIA:

 2.1.1.1 Patients must have histologically proven prostate adenocarcinoma confirmed by a
 CLIA certified laboratory.

 2.1.1.2 Must have prostate cancer with high risk features defined as:

 -  Gleason 8 and higher OR

 -  PSA > 20 ng/mL OR

 -  Clinical stage T3a (i.e. likely extraprostatic extension on MRI) or T3b

 2.1.1.3 Patients must be eligible for and must be planning to undergo radical prostatectomy
 and lymphadenectomy regardless of findings on 18F-DCFPyL PET/CT

 2.1.1.4 Men age greater than or equal to 18 years.

 2.1.1.5 ECOG performance status <2

 2.1.1.6 Patients must have adequate organ and marrow function as defined below:

 -  Hemoglobin greater than or equal to 9 g/dL

 -  leukocytes greater than or equal to 3,000/mcL

 -  platelets greater than or equal to 100,000/mcL

 -  total bilirubin <2 X normal institutional limits

 -  AST(SGOT)/ALT(SGPT) less than or equal to 3 X normal institutional limits

 -  creatinine <2 X normal institutional limits

 OR

 eGFR greater than or equal to 50 mL/min/1.73 m2 for patients with creatinine levels above
 institutional normal.

 2.1.1.7 Ability of subject to understand and the willingness to sign a written informed
 consent document.

 2.1.1.8 Willingness and ability to undergo biopsy of radiotracer-avid lesion if feasible.

 2.1.1.9 Willingness and ability to undergo multiparametric prostate MRI and 18F-DCFPyL
 PET/CT

 EXCLUSION CRITERIA

 2.1.2.1 Any investigational agents in the past 28 days prior to enrollment.

 2.1.2.2 Clinical stage T4 (tumor invades adjacent structures except seminal vesicles).

 2.1.2.3 Distant metastatic disease on conventional imaging studies (computed tomography
 (CT) of the abdomen and pelvis and 99mTc-methylene diphosphonate bone scan (bone scan)).
 NaF PET/CT scan cannot substitute for a bone scan. Given lack of specificity of CT for
 lymph node metastases at lower thresholds (34, 35), pelvic lymph nodes below 2 cm in the
 short axis are allowed.

 2.1.2.4 Any prior hormone therapy used to treat prostate cancer, except limited androgen
 receptor antagonist therapy, defined as less than or equal to 3 days of treatment. The
 medication must be discontinued within 5 half-lives of the compound prior to study entry.

 2.1.2.5 Any prior therapy for prostate cancer with surgery, radiation, and/or chemotherapy.

 2.1.2.6 Contraindication to MRI or PET:

 -  Patients weighing more than weight limit for the scanner tables or unable to fit
 within the imaging gantry

 -  Prior reaction to 18F-DCFPyL

 -  Patients with pacemakers, cerebral aneurysm clips, shrapnel injury or implantable
 electronic device that are not MRI compatible at 3 T

 -  Severe claustrophobia unresponsive to oral anxiolytics

 2.1.2.7 Uncontrolled intercurrent 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.

 2.1.2.8 Other medical conditions deemed by the principal investigator (or associates) to
 make the subject unsafe/ineligible for the protocol procedures or for radical
 prostatectomy.

 2.1.2.9 A malignancy within the past 3 years for which prostatectomy is a contraindication.

 2.1.2.10 Radiotracer administered within 5 half-lives prior to the date of 18F-DCFPyL
 PET/CT imaging.

 2.1.2.11 PSMA-targeted imaging within 6 months prior to the date of 18F-DCFPyL PET/CT
 imaging.

 2.1.2.12 Unable to refrain from fathering a child or donating sperm for 10 days after each
 18FDCFPyL injection.

 2.1.3 Recruitment Strategies