Gallium-68 PSMA-11 Positron Emission Tomography (PET) Imaging in Patients With Biochemical Recurrence

Gallium-68 PSMA-11 PET Imaging in Patients With Biochemical Recurrence

The investigators are imaging patients with prostate cancer using a new PET imaging agent (Ga-68-PSMA-11) in order to evaluate its ability to detection prostate cancer in patients with biochemical recurrence after prostatectomy and radiation therapy.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Ga-68 labeled PSMA-11 PET

• Study Type: Interventional
• Enrollment (Actual): 346
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria

• Histopathologically proven prostate adenocarcinoma.

• Rising prostate-specific antigen (PSA) (at least two consecutive rising PSAs) after definitive therapy with prostatectomy or radiation therapy (external beam or brachytherapy).

  • Post radical prostatectomy (RP) - American Urological Association (AUA) recommendation for biochemical recurrence after radical prostatectomy

    • PSA greater than or equal to 0.2 ng/mL measured more than 6 weeks after RP.

  • Post-radiation therapy -ASTRO-Phoenix consensus definition of biochemical recurrence after radiation therapy

    • Nadir + greater than or equal to 2 ng/mL rise in PSA
• Karnofsky performance status of > 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

• Unable to lie flat, still or tolerate a PET scan.
• Concomitant investigational therapy.
• Patient undergoing active treatment for non-prostate malignancy, other than skin basal cell or cutaneous superficial squamous cell carcinoma that has not metastasized and superficial bladder cancer.
• Contraindication to furosemide administration including prior allergy or adverse reaction to furosemide or sulfa drugs. (Note: This exclusion criteria can be removed if Furosemide is omitted as part of the PET imaging protocol if a second-generation scatter correction is available for the used PET device).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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-urea- Lys(Ahx)-HBED-CC; Ga-68 labeled HBED-CC PSMA; Ga-68 labeled Glu-NH-CO-NH- Lys(Ahx)-HBED-CC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
True Positive Rate for Detection of Tumor Location in Lymph Nodes Confirmed by Histopathology/Biopsy, Clinical and Conventional Imaging Follow-up	The true positive rate or detection rate (sensitivity) is defined as the proportion of all participants who have prostate cancer detected in the lymph nodes using Ga68-PSMA-11, where disease location is also confirmed by histopathology/biopsy, clinical and conventional imaging follow-up. Corresponding two-sided 95% confidence intervals will be constructed using the Wilson score method.	1 Day
True Positive Rate for Detection of Tumor Location in Visceral Tissue Confirmed by Histopathology/Biopsy, Clinical and Conventional Imaging Follow-up	The true positive rate or detection rate (sensitivity) is defined as the proportion of all participants who have prostate cancer detected in the visceral tissue using Ga68-PSMA-11, where disease location is also confirmed by histopathology/biopsy, clinical and conventional imaging follow-up. Corresponding two-sided 95% confidence intervals will be constructed using the Wilson score method.	1 Day
True Positive Rate for Detection of Tumor Location in Bone Tissue Confirmed by Histopathology/Biopsy, Clinical and Conventional Imaging Follow-up	The true positive rate or detection rate (sensitivity) is defined as the proportion of all participants who have prostate cancer detected in the bone tissue using Ga68-PSMA-11, where disease location is also confirmed by histopathology/biopsy, clinical and conventional imaging follow-up. Corresponding two-sided 95% confidence intervals will be constructed using the Wilson score method.	1 Day
True Positive Rate for Detection of Tumor Location in Prostate Bed Confirmed by Histopathology/Biopsy, Clinical and Conventional Imaging Follow-up	The true positive rate or detection rate (sensitivity) is defined as the proportion of all participants who have prostate cancer detected in the prostate bed using Ga68-PSMA-11, where disease location is also confirmed by histopathology/biopsy, clinical and conventional imaging follow-up. Corresponding two-sided 95% confidence intervals will be constructed using the Wilson score method.	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive Predictive Value (PPV) for Detection of Tumor Location in Lymph Nodes Confirmed by Histopathology/Biopsy, Clinical and Conventional Imaging Follow-up.	Positive predictive value is the probability that participants with a positive reading truly have prostate cancer in the lymph nodes as confirmed by by histopathology/biopsy, clinical and conventional imaging follow-up.	1 Day
PPV for Detection of Tumor Location in Visceral Lesions Confirmed by Histopathology/Biopsy, Clinical and Conventional Imaging Follow-up.	Positive predictive value is the probability that participants with a positive reading truly have prostate cancer in visceral tissue as confirmed by by histopathology/biopsy, clinical and conventional imaging follow-up.	1 Day
PPV for Detection of Tumor Location in Bone Metastasis Lesions Confirmed by Histopathology/Biopsy, Clinical and Conventional Imaging Follow-up.	Positive predictive value is the probability that participants with a positive reading truly have prostate cancer metastasized in the bone as confirmed by by histopathology/biopsy, clinical and conventional imaging follow-up.	1 Day
PPV for Detection of Tumor Location in Prostate Bed Confirmed by Histopathology/Biopsy, Clinical and Conventional Imaging Follow-up.	Positive predictive value is the probability that participants with a positive reading truly have prostate cancer in the prostate bed as confirmed by by histopathology/biopsy, clinical and conventional imaging follow-up.	1 Day
True Positive Rate for Detection of Tumor Location in Lymph Nodes Confirmed by Histology/Pathology Only	The true positive rate or detection rate (sensitivity) is defined as the proportion of all participants who have prostate cancer detected in the lymph nodes using Ga68-PSMA-11, where disease location is also confirmed by histopathology/biopsy only.	1 Day
True Positive Rate for Detection of Tumor Location in Visceral Tissue Confirmed by Histology/Pathology Only	The true positive rate or detection rate (sensitivity) is defined as the proportion of all participants who have prostate cancer detected in the visceral tissue using Ga68-PSMA-11, where disease location is also confirmed by histopathology/biopsy only.	1 Day
True Positive Rate for Detection of Tumor Location in Bone Tissue Confirmed by Histology/Pathology Only	The true positive rate or detection rate (sensitivity) is defined as the proportion of all participants who have prostate cancer detected in the bone tissue using Ga68-PSMA-11, where disease location is also confirmed by histopathology/biopsy only.	1 Day
True Positive Rate for Detection of Tumor Location in Prostate Bed Confirmed by Histology/Pathology Only	The true positive rate or detection rate is defined as the proportion of all participants who have prostate cancer detected in the prostate bed using Ga68-PSMA-11, where disease location is also confirmed by histopathology/biopsy only.	1 Day
PPV for Detection of Tumor Location in Lymph Nodes Confirmed by Histopathology/Biopsy Only	Positive predictive value is the probability that participants with a positive reading truly have prostate cancer in the lymph nodes as confirmed by by histopathology/biopsy	1 Day
PPV for Detection of Tumor Location in Visceral Tissue Confirmed by Histopathology/Biopsy Only	Positive predictive value is the probability that participants with a positive reading truly have prostate cancer in the visceral tissue as confirmed by by histopathology/biopsy	1 Day
PPV for Detection of Tumor Location in Bone Tissue Confirmed by Histopathology/Biopsy Only	Positive predictive value is the probability that participants with a positive reading truly have prostate cancer in the bone tissue as confirmed by by histopathology/biopsy	1 Day
PPV for Detection of Tumor Location in Prostate Bed Confirmed by Histopathology/Biopsy Only	Positive predictive value is the probability that participants with a positive reading truly have prostate cancer in the prostate bed as confirmed by by histopathology/biopsy	1 Day
Detection Rate of 68Ga-PSMA-11 PET Stratified by Prostate-specific Antigen (PSA) Value	Detection rate (sensitivity) on a per-patient basis of 68Ga-PSMA-11 PET stratified by PSA value (0.2- <0.5, 0.5 - <1.0, 1.0 - <2.0, 2.0 - <5.0, >=5.0) will be summarized in tabular format for participants with PSMA positive disease, independent of pathology, imaging or clinical follow-up.	1 Day
Detection Rate of 68Ga-PSMA-11 PET Stratified by Prior Cancer Treatment	Detection rates (sensitivity) on a per-patient basis of 68Ga-PSMA-11 PET stratified by prior cancer treatment (Prostatectomy, Radiation, or Prostatectomy plus Radiation) will be summarized in tabular format.	1 Day
Detection Rate of 68Ga-PSMA-11 PET Stratified by Prior Use of Androgen Deprivation Therapy (ADT)	Detection rate (sensitivity) on a per-patient basis of 68Ga-PSMA-11 PET stratified by prior use of ADT as a cancer treatment (Prior treatment with ADT, No prior treatment with ADT) will be summarized in tabular format.	1 Day
Percent of Participants With a Change in Clinical Management	Impact of 68Ga-PSMA-11 PET on clinical management in patients with biochemical recurrence (BCR) was measured using Pre-PET (Q1), post-PET (Q2), and post-treatment (Q3) questionnaires sent to referring physicians recording site of recurrence and intended (Q1 to Q2 change) and implemented (Q3) therapeutic and diagnostic management. Percentage of participants with a change in clinical management will be reported using descriptive statistics based on qualitative physician responses from the change in management surveys.	Up to 6 months
Rate of Inter-reader Reproducibility for Positivity	Inter-reader reproducibility for positivity at the patient level will be reported using the Fleiss' Kappa test for multiple readers	1 Day
Number of Participants With Grade 3 or Higher, Treatment-related Adverse Events	All grade 3 and above adverse events will be recorded using the NCI CTCAE v4.0. The Investigator will assign attribution of the possible association of the event with use of the investigational drug.	Up to 30 days

Collaborators and Investigators

• Sponsor: Thomas Hope

Publications and helpful links

General Publications

• Fendler WP, Calais J, Eiber M, Simko JP, Kurhanewicz J, Santos RD, Feng FY, Reiter RE, Rettig MB, Nickols NG, Kishan AU; PSMA PET Reader Group, Slavik R, Carroll PR, Lawhn-Heath C, Herrmann K, Czernin J, Hope TA. False positive PSMA PET for tumor remnants in the irradiated prostate and other interpretation pitfalls in a prospective multi-center trial. Eur J Nucl Med Mol Imaging. 2021 Feb;48(2):501-508. doi: 10.1007/s00259-020-04945-1. Epub 2020 Aug 17.
• Fendler WP, Calais J, Eiber M, Flavell RR, Mishoe A, Feng FY, Nguyen HG, Reiter RE, Rettig MB, Okamoto S, Emmett L, Zacho HD, Ilhan H, Wetter A, Rischpler C, Schoder H, Burger IA, Gartmann J, Smith R, Small EJ, Slavik R, Carroll PR, Herrmann K, Czernin J, Hope TA. Assessment of 68Ga-PSMA-11 PET Accuracy in Localizing Recurrent Prostate Cancer: A Prospective Single-Arm Clinical Trial. JAMA Oncol. 2019 Jun 1;5(6):856-863. doi: 10.1001/jamaoncol.2019.0096.

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2017
• Primary Completion (Actual): September 1, 2020
• Study Completion (Actual): September 1, 2020

Study Registration Dates

• First Submitted: November 21, 2017
• First Submitted That Met QC Criteria: November 21, 2017
• First Posted (Actual): November 27, 2017

Study Record Updates

• Last Update Posted (Actual): October 21, 2021
• Last Update Submitted That Met QC Criteria: September 22, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Recurrence; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Anticoagulants; Chelating Agents; Sequestering Agents; Calcium Chelating Agents; Edetic Acid; Gallium 68 PSMA-11
• Other Study ID Numbers: 175518; NCI-2018-00040 (Registry Identifier: NCI Clinical Trials Reporting Program)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified datasets were made available to collaborating researchers
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No