Gallium-68 PSMA-11 PET in Intermediate to High-risk Preprostatectomy Patients (PSMA PreRP)

• ClinicalTrials.gov Identifier: NCT02919111
• Recruitment Status: Completed
• First Posted: September 29, 2016
• Results First Posted: December 10, 2020
• Last Update Posted: December 10, 2020
• Sponsor: University of California, San Francisco
• Information provided by (Responsible Party): Thomas Hope, University of California, San Francisco

Study Description

Brief Summary:

The investigators are imaging patients with prostate cancer using a new PET imaging agent (Ga-68-PSMA-11) in order to evaluate it's ability to detection prostate cancer in patients with high risk disease prior to prostatectomy.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Drug: Ga-68 labeled PSMA-11 PET	Phase 2; Phase 3

Detailed Description:

Imaging and staging of prostate cancer is critical for surgical and treatment planning. Patients with suspected metastatic prostate cancer will be imaged using Gallium-68 labeled PSMA-11 in order to demonstrate its utility. The investigators plan to utilize this data to obtain further approvals of the Ga-68-PSMA-11 compound, so that this agent will become available for clinical imaging in prostate cancer patients. In the pre-prostatectomy population, the primary objective is to determine the sensitivity and specificity for detection on nodal metastasis.

This compound has been shown to be superior to choline based PET agents for the staging of prostate cancer, both Carbon-11 and Fluorine-18 compounds. But this compound was not patented and therefore no company or private entity will make the investment required to bring Ga-68-PSMA-11 to market. In the vacuum of availability, academic groups must take the lead in order to collect the necessary data for future FDA approval.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 299 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Gallium-68 PSMA-11 PET in Intermediate to High-risk Preprostatectomy Patients
• Actual Study Start Date: September 23, 2016
• Actual Primary Completion Date: December 31, 2019
• Actual Study Completion Date: December 31, 2019

Arms and Interventions

Arm

Intervention/treatment

Experimental: Ga-68 labeled PSMA-11 PET; PSMA PET imaging: Patients will receive Ga-68 labeled PSMA-11 PET and then undergo PET/CT or PET/MRI approximately 55-70 minutes later.

Drug: Ga-68 labeled PSMA-11 PET; Patients will be imaged using Ga-68 labeled PSMA-11 PET to determine if the presence of metastatic disease. Prostate Specific Membrane Antigen (PSMA) is a protein expressed on prostate cancer cells that can be imaged using small molecules that target this protocol.; Other Names: Ga-68 labeled DKFZ-PSMA-11; Ga-68 labeled Glu-NH-CO-NH- Lys(Ahx)-HBED-CC; Ga-68 labeled Glu-urea- Lys(Ahx)-HBED-CC; Ga-68 labeled HBED-CC PSMA

Outcome Measures

Primary Outcome Measures :

1. Sensitivity of PSMA PET for the Detection of Regional Nodal Metastases Compared to Pathology at Radical Prostatectomy [ Time Frame: Up to 1 year ]
   Sensitivity is defined as the ratio of the proportion of the patients who have the condition of interest and whose test results are positive over the number who have the disease. Patients who have a positive node on imaging and on pathology will be considered a true-positive. Patients who have no nodes on imaging and pathology will be considered true-negatives. Patients with positive nodes on imaging and negative on pathology will be considered false positives and those with positive nodes on pathology but negative on imaging will be considered false negatives. Follow-up scans for up to one year can be used in analysis
2. Specificity of of PSMA PET for the Detection of Regional Nodal Metastases Compared to Pathology at Radical Prostatectomy [ Time Frame: Up to 1 year ]
   Specificity is defined as the number of non-diseased participants correctly classified divided by all non-diseased individuals. Patients who have a positive node on imaging and on pathology will be considered a true-positive. Patients who have no nodes on imaging and pathology will be considered true-negatives. Patients with positive nodes on imaging and negative on pathology will be considered false positives and those with positive nodes on pathology but negative on imaging will be considered false negatives. Follow-up scans for up to one year can be used in analysis
3. Positive Predictive Value (PPV) of of PSMA PET for the Detection of Regional Nodal Metastases Compared to Pathology at Radical Prostatectomy [ Time Frame: Up to 1 year ]
   PPV is the proportion of patients with positive test who actually have the disease. Patients who have a positive node on imaging and on pathology will be considered a true-positive. Patients who have no nodes on imaging and pathology will be considered true-negatives. Patients with positive nodes on imaging and negative on pathology will be considered false positives and those with positive nodes on pathology but negative on imaging will be considered false negatives. Follow-up scans for up to one year can be used in analysis
4. Negative Predictive Value (NPV) of PSMA PET for the Detection of Regional Nodal Metastases Compared to Pathology at Radical Prostatectomy [ Time Frame: Up to 1 year ]
   NPV is the ratio of participants truly diagnosed as negative to all those who had negative test results. Patients who have a positive node on imaging and on pathology will be considered a true-positive. Patients who have no nodes on imaging and pathology will be considered true- negatives. Patients with positive nodes on imaging and negative on pathology will be considered false positives and those with positive nodes on pathology but negative on imaging will be considered false negatives. Follow-up scans for obtained up to one year after study scan be used in analysis.

Secondary Outcome Measures :

1. Number of Participants With Grade 3 Treatment-related Adverse Events [ Time Frame: Up to 3 days ]
   All grade 3 and above adverse events were recorded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. The Investigator assigns grade, attribution of the possible association of the event with use of the investigational drug. The safety parameters include spontaneous reports of adverse events reported to the investigator by patients
2. Sensitivity of PSMA PET for the Detection of Extra-pelvic Nodal Metastases [ Time Frame: Up to 1 year ]
   Gallium 68 labeled PSMA-11 (68Ga-PSMA-11) positive lymph nodes will be considered for detection of extra-pelvic nodal metastases and assessed by change in size. Participants who if on follow-up imaging within 3-12 months, have lymph nodes which decrease by more than 30% or increase by more than 20% in short axis diameter (with a minimum of 3 mm in change in size) or with solitary lymph node regions show a decrease of Prostate-specific antigen (PSA) by >50% after targeted treatment and the lymph nodes do not change in size (less than 30% decrease or less than 20% increase in short axis diameter) will be counted as true positives. If on follow-up imaging, sites of initial 68Ga-PSMA-11 positive lymph node lesions < 30% without systemic therapy or focal therapy at this site or if 68Ga-PSMA-11 positive lymph node lesions that do not meet criteria for above false positive or true positive will be counted as false positives.
3. Specificity of PSMA PET for the Detection of Extra-pelvic Nodal Metastases [ Time Frame: Up to 1 year ]
   68Ga-PSMA-11 positive lymph nodes will be considered for detection of extra-pelvic nodal metastases and assessed by change in size. Participants who if on follow-up imaging within 3-12 months, have lymph nodes which decrease by more than 30% or increase by more than 20% in short axis diameter (with a minimum of 3 mm in change in size) or with solitary lymph node regions show a decrease of PSA by >50% after targeted treatment and the lymph nodes do not change in size (less than 30% decrease or less than 20% increase in short axis diameter) will be counted as true positives. If on follow-up imaging, sites of initial 68Ga-PSMA-11 positive lymph node lesions < 30% without systemic therapy or focal therapy at this site or if 68Ga-PSMA-11 positive lymph node lesions that do not meet criteria for above false positive or true positive will be counted as false positives.
4. Positive Predictive Value of PSMA PET for the Detection of Extra-pelvic Nodal Metastases [ Time Frame: Up to 1 year ]
   68Ga-PSMA-11 positive lymph nodes will be considered for detection of extra-pelvic nodal metastases and assessed by change in size. Participants who if on follow-up imaging within 3-12 months, have lymph nodes which decrease by more than 30% or increase by more than 20% in short axis diameter (with a minimum of 3 mm in change in size) or with solitary lymph node regions show a decrease of PSA by >50% after targeted treatment and the lymph nodes do not change in size (less than 30% decrease or less than 20% increase in short axis diameter) will be counted as true positives. If on follow-up imaging, sites of initial 68Ga-PSMA-11 positive lymph node lesions < 30% without systemic therapy or focal therapy at this site or if 68Ga-PSMA-11 positive lymph node lesions that do not meet criteria for above false positive or true positive will be counted as false positives.
5. Negative Predictive Value of PSMA PET for the Detection of Extra-pelvic Nodal Metastases [ Time Frame: Up to 1 year ]
   68Ga-PSMA-11 positive lymph nodes will be considered for detection of extra-pelvic nodal metastases and assessed by change in size. Participants who if on follow-up imaging within 3-12 months, have lymph nodes which decrease by more than 30% or increase by more than 20% in short axis diameter (with a minimum of 3 mm in change in size) or with solitary lymph node regions show a decrease of PSA by >50% after targeted treatment and the lymph nodes do not change in size (less than 30% decrease or less than 20% increase in short axis diameter) will be counted as true positives. If on follow-up imaging, sites of initial 68Ga-PSMA-11 positive lymph node lesions < 30% without systemic therapy or focal therapy at this site or if 68Ga-PSMA-11 positive lymph node lesions that do not meet criteria for above false positive or true positive will be counted as false positives.
6. Sensitivity of PSMA PET for the Detection of Visceral Metastases [ Time Frame: Up to 1 year ]
   Visceral lesions (non-lymph node soft tissue or organ) will be assessed by change in size. 68Ga-PSMA-11 positive visceral lesions will be considered True positive if on follow-up imaging within 3-12 months, visceral lesions seen on imaging decrease by 30% (for patients undergoing systemic treatment of focal therapy at this site) or increase by 20% in largest diameter or if participants with solitary visceral metastasis show a decrease of PSA by greater than 50% after targeted treatment and lesions do not change in size (less than 30% decrease or 20% increase in largest diameter) and False positive if on follow-up imaging within 3-12 months, sites of initial 68Ga-PSMA-11 positive visceral lesions seen on CT or MRI decrease by more than 30% without systemic therapy or focal therapy at this site or if 68Ga-PSMA-11 positive visceral lesions do not meet the criteria for above false positive or true positive findings.
7. Specificity of PSMA PET for the Detection of Visceral Metastases [ Time Frame: Up to 1 year ]
   Visceral lesions (non-lymph node soft tissue or organ) will be assessed by change in size. 68Ga-PSMA-11 positive visceral lesions will be considered True positive if on follow-up imaging within 3-12 months, visceral lesions seen on imaging decrease by 30% (for patients undergoing systemic treatment of focal therapy at this site) or increase by 20% in largest diameter or if participants with solitary visceral metastasis show a decrease of PSA by greater than 50% after targeted treatment and lesions do not change in size (less than 30% decrease or 20% increase in largest diameter) and False positive if on follow-up imaging within 3-12 months, sites of initial 68Ga-PSMA-11 positive visceral lesions seen on CT or MRI decrease by more than 30% without systemic therapy or focal therapy at this site or if 68Ga-PSMA-11 positive visceral lesions do not meet the criteria for above false positive or true positive findings.
8. Positive Predictive Value of PSMA PET Visceral Metastases [ Time Frame: Up to 1 year ]
   Visceral lesions (non-lymph node soft tissue or organ) will be assessed by change in size. 68Ga-PSMA-11 positive visceral lesions will be considered True positive if on follow-up imaging within 3-12 months, visceral lesions seen on imaging decrease by 30% (for patients undergoing systemic treatment of focal therapy at this site) or increase by 20% in largest diameter or if participants with solitary visceral metastasis show a decrease of PSA by greater than 50% after targeted treatment and lesions do not change in size (less than 30% decrease or 20% increase in largest diameter) and False positive if on follow-up imaging within 3-12 months, sites of initial 68Ga-PSMA-11 positive visceral lesions seen on CT or MRI decrease by more than 30% without systemic therapy or focal therapy at this site or if 68Ga-PSMA-11 positive visceral lesions do not meet the criteria for above false positive or true positive findings.
9. Negative Predictive Value of PSMA PET for the Detection of Visceral Metastases [ Time Frame: Up to 1 year ]
   Visceral lesions (non-lymph node soft tissue or organ) will be assessed by change in size. 68Ga-PSMA-11 positive visceral lesions will be considered True positive if on follow-up imaging within 3-12 months, visceral lesions seen on imaging decrease by 30% (for patients undergoing systemic treatment of focal therapy at this site) or increase by 20% in largest diameter or if participants with solitary visceral metastasis show a decrease of PSA by greater than 50% after targeted treatment and lesions do not change in size (less than 30% decrease or 20% increase in largest diameter) and False positive if on follow-up imaging within 3-12 months, sites of initial 68Ga-PSMA-11 positive visceral lesions seen on CT or MRI decrease by more than 30% without systemic therapy or focal therapy at this site or if 68Ga-PSMA-11 positive visceral lesions do not meet the criteria for above false positive or true positive findings.
10. Sensitivity of PSMA PET for the Detection of Osseous Metastases [ Time Frame: Up to 1 year ]
    68Ga-PSMA-11 positive bone lesions will be considered a True positive if there was a corresponding positive sclerotic lesion on the CT portion of the 68Ga-PSMA-11 PET in the same location as the PSMA uptake, If there is focal uptake seen in the same location as the PSMA uptake on the baseline bone scan performed within one month of 68Ga-PSMA-11 PET, if there is a lesion noted in the same location as the PSMA uptake on the initial MRI performed within one month of 68Ga-PSMA-11 PET, if within 12 months follow-up CT demonstrates development of sclerosis in the same location as the PSMA uptake, if within 12 months follow-up MRI demonstrates a new bone lesion in the same location as the PSMA uptake, if within 12 months follow-up bone scan demonstrates new focal uptake in the same location as the PSMA uptake and a False positive if 68Ga-PSMA-11 positive bone lesions do not meet the criteria for true positive findings.
11. Specificity of PSMA PET for the Detection of Osseous Metastases [ Time Frame: Up to 1 year ]
    68Ga-PSMA-11 positive bone lesions will be considered a True positive if there was a corresponding positive sclerotic lesion on the CT portion of the 68Ga-PSMA-11 PET in the same location as the PSMA uptake, If there is focal uptake seen in the same location as the PSMA uptake on the baseline bone scan performed within one month of 68Ga-PSMA-11 PET, if there is a lesion noted in the same location as the PSMA uptake on the initial MRI performed within one month of 68Ga-PSMA-11 PET, if within 12 months follow-up CT demonstrates development of sclerosis in the same location as the PSMA uptake, if within 12 months follow-up MRI demonstrates a new bone lesion in the same location as the PSMA uptake, if within 12 months follow-up bone scan demonstrates new focal uptake in the same location as the PSMA uptake and a False positive if 68Ga-PSMA-11 positive bone lesions do not meet the criteria for true positive findings.
12. Positive Predictive Value of PSMA PET for the Detection of Osseous Metastases [ Time Frame: Up to 1 year ]
    68Ga-PSMA-11 positive bone lesions will be considered a True positive if there was a corresponding positive sclerotic lesion on the CT portion of the 68Ga-PSMA-11 PET in the same location as the PSMA uptake, If there is focal uptake seen in the same location as the PSMA uptake on the baseline bone scan performed within one month of 68Ga-PSMA-11 PET, if there is a lesion noted in the same location as the PSMA uptake on the initial MRI performed within one month of 68Ga-PSMA-11 PET, if within 12 months follow-up CT demonstrates development of sclerosis in the same location as the PSMA uptake, if within 12 months follow-up MRI demonstrates a new bone lesion in the same location as the PSMA uptake, if within 12 months follow-up bone scan demonstrates new focal uptake in the same location as the PSMA uptake and a False positive if 68Ga-PSMA-11 positive bone lesions do not meet the criteria for true positive findings.
13. Negative Predictive Value of PSMA PET for the Detection of Osseous Metastases [ Time Frame: Up to 1 year ]
    68Ga-PSMA-11 positive bone lesions will be considered a True positive if there was a corresponding positive sclerotic lesion on the CT portion of the 68Ga-PSMA-11 PET in the same location as the PSMA uptake, If there is focal uptake seen in the same location as the PSMA uptake on the baseline bone scan performed within one month of 68Ga-PSMA-11 PET, if there is a lesion noted in the same location as the PSMA uptake on the initial MRI performed within one month of 68Ga-PSMA-11 PET, if within 12 months follow-up CT demonstrates development of sclerosis in the same location as the PSMA uptake, if within 12 months follow-up MRI demonstrates a new bone lesion in the same location as the PSMA uptake, if within 12 months follow-up bone scan demonstrates new focal uptake in the same location as the PSMA uptake and a False positive if 68Ga-PSMA-11 positive bone lesions do not meet the criteria for true positive findings.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Biopsy proven prostate adenocarcinoma.
• Planned prostatectomy with lymph node dissection.
• Intermediate to high-risk disease (as determined by elevated Prostate-specific antigen (PSA) [PSA>10], T-stage [T2b or greater], Gleason score [Gleason score > 6] or other risk factors).
• Diagnostic CT or MRI as part of the PET study or performed within one month of PSMA PET.
• Karnofsky performance status of greater than 50 (or Eastern Cooperative Oncology Group (ECOG) /World Health Organization (WHO) equivalent).
• Age > 18.
• Ability to understand a written informed consent document, and the willingness to sign it.

Exclusion Criteria:

• Patients not capable of getting PET study due to weight, claustrophobia, or inability to lay still for the duration of the exam.
• Neoadjuvant chemotherapy or radiation therapy prior to prostatectomy.
• Including focal ablation techniques (HiFu).
• Androgen deprivation therapy or other neoadjuvant treatments prior to PET imaging and surgery.

Contacts and Locations

Locations

United States, California

University of California, San Francisco

San Francisco, California, United States, 94107

Sponsors and Collaborators

University of California, San Francisco

Investigators

• Principal Investigator: Thomas Hope, MD; University of California, San Francisco

  Study Documents (Full-Text)

Documents provided by Thomas Hope, University of California, San Francisco:

Study Protocol and Statistical Analysis Plan  [PDF] June 8, 2018

Informed Consent Form  [PDF] October 18, 2017

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Hope TA, Eiber M, Armstrong WR, Juarez R, Murthy V, Lawhn-Heath C, Behr SC, Zhang L, Barbato F, Ceci F, Farolfi A, Schwarzenböck SM, Unterrainer M, Zacho HD, Nguyen HG, Cooperberg MR, Carroll PR, Reiter RE, Holden S, Herrmann K, Zhu S, Fendler WP, Czernin J, Calais J. Diagnostic Accuracy of 68Ga-PSMA-11 PET for Pelvic Nodal Metastasis Detection Prior to Radical Prostatectomy and Pelvic Lymph Node Dissection: A Multicenter Prospective Phase 3 Imaging Trial. JAMA Oncol. 2021 Nov 1;7(11):1635-1642. doi: 10.1001/jamaoncol.2021.3771.

• Responsible Party: Thomas Hope, Assistant Professor of Radiology and Biomedical Imaging, University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT02919111
• Other Study ID Numbers: 16559; NCI-2018-00038 ( Registry Identifier: NCI Clinical Trials Reporting Program (CTRP) )
• First Posted: September 29, 2016
• Results First Posted: December 10, 2020
• Last Update Posted: December 10, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases; Edetic Acid; Chelating Agents; Sequestering Agents; Molecular Mechanisms of Pharmacological Action; Anticoagulants; Calcium Chelating Agents