PSMA-PET Registry for Recurrent Prostate Cancer (PREP)

• ClinicalTrials.gov Identifier: NCT03718260
• Recruitment Status: Recruiting
• First Posted: October 24, 2018
• Last Update Posted: October 5, 2020
• Sponsor: Lawson Health Research Institute
• Collaborators: Cancer Care Ontario; Centre for Probe Development and Commercialization
• Information provided by (Responsible Party): Lawson Health Research Institute

Study Description

Brief Summary:

This study aims to institute a province-wide registry leveraging the availability of a new Positron Emission Tomography tracer, [18F]-DCFPyL and PET expertise across Ontario centers to improve our ability to characterize patterns of recurrence and personalize therapies in men with recurrent prostate cancer after primary treatment.

Condition or disease	Intervention/treatment	Phase
Recurrent Prostate Cancer	Diagnostic Test: [18F]-DCFPyL PET/ CT scan (PSMA PET)	Not Applicable

Detailed Description:

This registry study will provide Ontario centres access to a new Positron Emission Tomography (PET) tracer, [18F]-DCFPyL, to improve our ability to identify areas of prostate cancer recurrence in men who have undergone surgical removal of their prostate gland (radical prostatectomy) or radiation of their prostate (external beam radiation, brachytherapy or a combination of both) and there is a suspicion of recurrence of the cancer. Men with suspected persistent or recurrent disease can be identified on the basis of a rising Prostate Specific Antigen (PSA) blood test, or the presence of node positive disease at the time of their surgery, or a PSA blood test continues to be detectable within 3 months after their surgery. It is the aim of this study to determine if [18F]-DCFPyL PET/CT can potentially identify areas of prostate cancer recurrence not seen with usual imaging (bone scan/CT scans) and impact the management of the disease. A report of the results of the [18F]-DCFPyL PET/CT will be provided to the participating physicians to determine a treatment plan. As part of the patient eligibility for [18F]-DCFPyL PET/CT participating physicians will complete a questionnaire after the [18F]-DCFPyL PET/CT information is provided to report how the results impact patient management. Actual interventions following completion of the [18F]-DCFPyL PET/CT will be tracked by linkage to provincial registries. Six centres across Ontario will participate in the registry study which is expected to take 4 years to complete with an additional one year of follow-up to capture patient outcomes.

PREP Phase 2 was initiated to investigate the hypothesis that conventional imaging is not adding to the information provided by PSMA PET/CT alone. PREP Phase 2 will retain the same study design as Phase I but will remove bone scan and computed tomography as criteria for entry into the study except for those patients with higher PSA (>10 ng/ml).

Identical cohort sizes will be accrued in Phase 2 to permit comparison of detection rates with similar confidence intervals with and without conventional imaging. Transition to PREP Phase 2 occurred when overall accrual to PREP exceeded 80% of target.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 3070 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: PSMA-PET Registry for Recurrent Prostate Cancer
• Actual Study Start Date: September 27, 2018
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: December 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1; Men who are node positive or who have persistently detectable PSA after initial radical prostatectomy will be restaged with [18F]-DCFPyL PET/ CT scan (PSMA PET)	Diagnostic Test: [18F]-DCFPyL PET/ CT scan (PSMA PET); Participants will undergo re-staging with [18F]-DCFPyL PET/CT Scan (PSMA PET).
Experimental: Cohort 2; Men with biochemical failure after initial prostatectomy will be restaged with [18F]-DCFPyL PET/ CT scan (PSMA PET)	Diagnostic Test: [18F]-DCFPyL PET/ CT scan (PSMA PET); Participants will undergo re-staging with [18F]-DCFPyL PET/CT Scan (PSMA PET).
Experimental: Cohort 3; Men with biochemical failure after initial radical prostatectomy and salvage radiotherapy will be restaged with [18F]-DCFPyL PET/ CT scan (PSMA PET)	Diagnostic Test: [18F]-DCFPyL PET/ CT scan (PSMA PET); Participants will undergo re-staging with [18F]-DCFPyL PET/CT Scan (PSMA PET).
Experimental: Cohort 4; Men with biochemical failure after initial radical prostatectomy with or without adjuvant/ salvage radiotherapy who are currently on salvage hormone therapy will be restaged with [18F]-DCFPyL PET/ CT scan (PSMA PET)	Diagnostic Test: [18F]-DCFPyL PET/ CT scan (PSMA PET); Participants will undergo re-staging with [18F]-DCFPyL PET/CT Scan (PSMA PET).
Experimental: Cohort 5; Men who have prior PSMA directed treatment for oligometastatic disease, such as lesion directed therapy (e.g. stereotactic radiosurgery) or systemic therapy (e.g. hormone therapy or chemotherapy) with subsequent biochemical failure will be restaged with [18F]-DCFPyL PET/ CT scan (PSMA PET)	Diagnostic Test: [18F]-DCFPyL PET/ CT scan (PSMA PET); Participants will undergo re-staging with [18F]-DCFPyL PET/CT Scan (PSMA PET).
Experimental: Cohort 6; Men with biochemical failure after primary radiation therapy (external beam, brachytherapy or combinations together with or without hormone therapy) will be restaged with [18F]-DCFPyL PET/ CT scan (PSMA PET)	Diagnostic Test: [18F]-DCFPyL PET/ CT scan (PSMA PET); Participants will undergo re-staging with [18F]-DCFPyL PET/CT Scan (PSMA PET).
Experimental: Cohort 7; [18F]-DCFPyL as a problem-solving tool in patients with prostate cancer when confirmation of the site of disease and/or disease extent may impact clinical management. Patients in this cohort require approval from an independent adjudication by Cancer Care Ontario.	Diagnostic Test: [18F]-DCFPyL PET/ CT scan (PSMA PET); Participants will undergo re-staging with [18F]-DCFPyL PET/CT Scan (PSMA PET).

Outcome Measures

Primary Outcome Measures :

1. Frequency of disease detection on PSMA PET [ Time Frame: 5 years ]

   Phase 1: The number of men with detectable lesions on PSMA PET who have suspected recurrent or persistent disease post radical prostatectomy with or without adjuvant or salvage pelvic radiotherapy or hormone therapy as well as men treated with primary radiotherapy will be measured

   Phase 2: The number of men with detectable lesions on PSMA PET who have suspected recurrent or persistent disease post radical prostatectomy with or without adjuvant or salvage pelvic radiotherapy or hormone therapy as well as men treated with primary radiotherapy will be measured when PSMA PET/CT is used without routine pre-screening with conventional imaging.

Secondary Outcome Measures :

1. To determine correlations between PSA levels at time of imaging and presence of disease detected on PSMA PET. [ Time Frame: 5 years ]
   The likelihood of disease detected on PSMA PET will be correlated with absolute PSA level at the time of PSMA PET as supplied on the eligibility form.
2. Proportion of men with oligometastatic recurrence (four or fewer sites including the prostate bed if positive) confirmed on PSMA PET/CT [ Time Frame: 5 years ]
   Number of men with four or fewer sites of disease detected on PSMA PET
3. Number of men who have their management plan changed because of PSMA PET results [ Time Frame: 5 years ]
   The number of men who have a change in management as indicated by responses from referring physicians on an impact questionnaire completed after PSMA PET scans are reported.
4. To determine the actual management delivered within 6 months of PSMA PET [ Time Frame: 5 years ]

   Actual management within 6 months will be determined through linkage to existing health information registries and will include:

   1. Delivery of radiotherapy (anatomic site, dose and fractionation) - Cancer Care Ontario
   2. Biopsy of suspected recurrences (anatomic site, histology) - Provincial pathology database
   3. Use of salvage lymph node dissections - CIHI
   4. Use of salvage hormonal therapy/androgen deprivation
5. Compare PSA response at 6 months against PSA at the time of PSMA PET [ Time Frame: 5 years ]
   PSA response will be examined by comparing 6 month PSA against PSA at the time of PSMA PET through the Ontario Laboratory Information Services and correlated with actual management as determined in Outcome 5.
6. Compare the detection rates of PSMA PET/CT when conventional imaging is used as part of the eligibility criteria (PREP) versus when conventional imaging is omitted (PREP Phase 2) [ Time Frame: 5 years ]
   Number of men with detectable lesions as determined in the primary objective for PREP will be compared to the number of men with detectable lesions as determined in primary objective for PREP Phase 2.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Participants must be male (prostate cancer)
• Accepts Healthy Volunteers: No

Criteria

Phase 2

Inclusion Criteria:

1. Written informed consent obtained
2. Male, Age ≥ 18 years
3. Prior primary treatment for prostate cancer with curative intent such as radical prostatectomy or radiotherapy for localized prostate cancer. Unless PET/CT requested as part of Cohort 7.

4. Suspected persistent or recurrent disease defined as one of the following (unless PET/CT requested as part of Cohort 7):

   1. High risk disease at the time of radical prostatectomy characterized by pathologically involved node(s) or persistently detectable PSA (>0.1ng/ml) within 3 months post-surgery
   2. Primary treatment for prostate cancer and biochemical failure (BF) with current management according to the following:

   i. Following primary radical prostatectomy, BF is defined as rising PSA on at least 2 occasions measured at least 1 month apart and with the most recent PSA measured at >0.1 ng/ml

   ii. Following primary radiotherapy for localized disease, BF is defined according to the Phoenix Definition, which is rising PSA on at least 2 occasions measured at least 1 month apart and with the most recent PSA measured greater than the nadir PSA + 2.0 ng/ml

5. Patient scenario falls into one of the 7 pre-defined cohorts. When patient scenario falls outside cohorts 1-6 participation in the Registry must be approved through the established CCO adjudication process for Cohort 7.
6. Karnofsky performance status 70 or better (ECOG 0, 1).
7. If PSA >10 mg/mL, conventional imaging consisting of bone scan and abdo-pelvic CT scan within 3 months of registration that is either equivocal, negative (no lesions) or positive for oligometastatic disease (4 or fewer unequivocal lesions identified).

Exclusion Criteria:

1. Prostate cancer with significant sarcomatoid or spindle cell or neuroendocrine small cell components.
2. Prior PSMA PET scan within 6 months of enrollment.
3. Patient cannot lie still for at least 60 minutes or comply with imaging.
4. Patients falling outside of Cohorts 1-6 where independent adjudication by CCO does not support participation in the Registry.

Contacts and Locations

Contacts

Contact: Catherine Hildebrand, PhD, Project Coordinator; 519-685-8500 ext 53535; catherine.hildebrand@lhsc.on.ca

Locations

Canada, Ontario

St. Joseph's Healthcare Hamilton; Recruiting

Hamilton, Ontario, Canada, L8N 4A6

Contact: Research Coordinator- Camilla Tajzler 905-522-1155 ext 35876 tajzlec@mcmaster.ca

Principal Investigator: Anil Kapoor, MD, FRCSC

Sub-Investigator: Bobby Shayegan, MD, FRCSC

London Health Sciences Centre; Recruiting

London, Ontario, Canada, N6A 5W9

Contact: Clinical Research Associate- Stephanie Horst 519-685-8500 ext 56601 stephanie.horst@lhsc.on.ca

Principal Investigator: Joseph Chin, MD, FRCSC

Sub-Investigator: Glenn Bauman, MD, FRCPC

The Ottawa Hospital, General Campus; Recruiting

Ottawa, Ontario, Canada, K1H 8L6

Contact: Clinical Research Assistant- David Yachnin 613-798-5555 ext 74639 dyachnin@ohri.ca

Principal Investigator: Luke Lavallee, MDCM, FRCSC

Sub-Investigator: Eugene Leung, MD, FRCPC

Sub-Investigator: Chris Morash, MD, FRCSC

Thunder Bay Regional Health Sciences Centre; Recruiting

Thunder Bay, Ontario, Canada, P7B 6V4

Contact: Clinical Research Coordinator- Lori Moon, RN 807-684-7226 moonl@tbh.net

Principal Investigator: Marlon Hagerty, MD

Sub-Investigator: Walid Shahrour, MD, RCPSC

Sub-Investigator: Jonathan Boekhoud, MD, FRCPC

Toronto Sunnybrook Cancer Centre; Recruiting

Toronto, Ontario, Canada, M4N 3M5

Contact: Clinical Trial Coordinator- Marlene Kebabdjian 416-480-6100 ext 2890 Marlene.Kebabdjian@sunnybrook.ca

Principal Investigator: Laurence Klotz, MD, FRCSC

Sub-Investigator: Robert Wolfson, MD

Princess Margaret Cancer Centre, University Health Network; Recruiting

Toronto, Ontario, Canada, M5G 2M9

Contact: Clinical Research Coordinator- Linda Chan 416-946-4501 ext 5734 Linda.Chan@uhn.ca

Principal Investigator: Antonio Finelli, MD, FRCSC

Sub-Investigator: Ur Metser, MD, FRCPC

Sponsors and Collaborators

Lawson Health Research Institute

Cancer Care Ontario

Centre for Probe Development and Commercialization

Investigators

• Principal Investigator: Glenn Bauman, MD, FRCPC; Lawson Health Research Institute
• Principal Investigator: Ur Metser, MD, FRCPC; University Health Network, Toronto

More Information

Additional Information:

• Responsible Party: Lawson Health Research Institute
• ClinicalTrials.gov Identifier: NCT03718260
• Other Study ID Numbers: 4826
• First Posted: October 24, 2018
• Last Update Posted: October 5, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

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

Keywords provided by Lawson Health Research Institute:

Prostate Cancer; Biochemical Failure; Node positive; PSMA-PET; [18F]DCFPyL PET/CT imaging; Radical Prostatectomy; Radiation Therapy

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases