Prostate Specific Membrane Antigen (PMSA)-Based PET Imaging of High Risk Prostate Cancer

• ClinicalTrials.gov Identifier: NCT03976843
• Recruitment Status: Recruiting
• First Posted: June 6, 2019
• Last Update Posted: May 6, 2024
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Tracking Information

• First Submitted Date: June 5, 2019
• First Posted Date: June 6, 2019
• Last Update Posted Date: May 6, 2024
• Actual Study Start Date: December 4, 2019
• Estimated Primary Completion Date: August 31, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 5, 2019)

progression free survival [ Time Frame: 6 weeks, 3,6,9,12, and 18 months, 2,3, and 4 years ]

progression-free survival which is improved over that of historical data from a general population

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 8, 2020)

progression free survival [ Time Frame: 6 weeks, 3,6,9,12, and 18 months, 2,3, and 4 years ]

progression-free survival of patients with an 18F-DCFPyL PET/CT that is positive for metastases

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Prostate Specific Membrane Antigen (PMSA)-Based PET Imaging of High Risk Prostate Cancer
• Official Title: A Phase II Multi-Institutional Trial to Evaluate Prostate Specific Membrane Antigen (PMSA)-Based PET Imaging of High Risk Prostate Cancer

Brief Summary

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.

Detailed Description

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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic
• Condition: Prostate Cancer

Intervention

Drug: 18F-DCFPyL

18F-labeled agent that is a high affinity small molecule inhibitor of PSMA to detect prostate cancer via PET imaging

Study Arms

Experimental: 1/18F-DCFPyL PET/CT + radical prostatectomy

18F-DCFPyL PET/CT with radical prostatectomy and lymphadenectomy

Intervention: Drug: 18F-DCFPyL

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 19, 2023): 201
• Original Estimated Enrollment (submitted: June 5, 2019): 200
• Estimated Study Completion Date: August 31, 2025
• Estimated Primary Completion Date: August 31, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

• INCLUSION CRITERIA:
• Patients must have histologically proven prostate adenocarcinoma confirmed by a CLIA certified laboratory.

• 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
• Patients must be eligible for and must be planning to undergo radical prostatectomy and lymphadenectomy regardless of findings on 18F-DCFPyL PET/CT
• Men age greater than or equal to 18 years.
• ECOG performance status <2

• 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.

• Ability of subject to understand and the willingness to sign a written informed consent document.
• Willingness and ability to undergo biopsy of radiotracer-avid lesion if feasible.
• Willingness and ability to undergo multiparametric prostate MRI and 18F-DCFPyL PET/CT

EXCLUSION CRITERIA:

• Any investigational agents in the past 28 days prior to enrollment.
• Clinical stage T4 (tumor invades adjacent structures except seminal vesicles).
• Distant metastatic disease on conventional imaging studies (computed tomography (CT)) of the abdomen and pelvis and 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, pelvic lymph nodes below 2 cm in the short axis are allowed.
• 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.
• Any prior therapy for prostate cancer with surgery, radiation, and/or chemotherapy.

• 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
• 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.
• Other medical conditions deemed by the principal investigator (or associates) to make the subject unsafe/ineligible for the protocol procedures or for radical prostatectomy.
• A malignancy within the past 3 years for which prostatectomy is a contraindication.
• Radiotracer administered within 5 half-lives prior to the date of 18F-DCFPyL PET/CT imaging.
• PSMA-targeted imaging within 6 months with 18F-DCFPyL tracer prior to the date of 18F-DCFPyL PET/CT imaging. Participants can have PSMA targeted imaging with Gallium.
• Unable to refrain from fathering a child or donating sperm for 10 days after each 18FDCFPyL injection.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Michele L Reed, R.N.; (240) 760-6121; michele.reed@nih.gov

Contact: Fatima H Karzai, M.D.; (301) 480-7174; fatima.karzai@nih.gov

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03976843
• Other Study ID Numbers: 190104; 19-C-0104
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: .All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Time Frame: Clinical data available during the study and indefinitely.@@@@@@Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.@@@@@@Genomic data are made available via dbGaP through requests to the data custodians.@@@@@@Requests for all collected IPD data from clinical trials, conducted under a binding collaborative agreement between NCI/DCTD and a pharmaceutical/biotechnology company, that are not under DSMB monitoring must be in compliance with the terms of the binding collaborative agreement and must be approved by NCI/DCTD and the Pharmaceutical Collaborator (i.e., the NCI ETCTN Director in conjunction with the NCI/DCTD Regulatory Affairs Branch).

• Current Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
• Original Responsible Party: Same as current
• Current Study Sponsor: National Cancer Institute (NCI)
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Fatima H Karzai, M.D.; National Cancer Institute (NCI)

• PRS Account: National Institutes of Health Clinical Center (CC)
• Verification Date: April 30, 2024