A Pilot Study of [Ga-68]PSMA PET/MRI for the Assessment of PSMA-positive Tumors

The purpose of this study is to see if positron emission tomography/ magnetic resonance imaging (PET/MRI) can be used to monitor the effectiveness of cancer treatment using an investigational radioactive drug called [Ga-68]PSMA.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Lung Cancer; Prostate Cancer; Prostate-specific Membrane Antigen Positive Tumors
• Intervention / Treatment: Device: [Ga-68]PSMA PET/MR

Detailed Description

Primary Objective

The primary objective of this pilot imaging study is to determine the feasibility of using positron emission tomography/ magnetic resonance (PET/MR) with [Ga-68] prostate-specific membrane antigen (PSMA) for staging and treatment monitoring of PSMA expressing tumors. [Ga-68]PSMA PET/MR findings will be compared with standard of care imaging, patient follow up, and histopathology if available. [Ga-68]PSMA PET/MR will not be used to change the patients' treatment plan. Investigators will assess PET/MR test-retest reproducibility and compare baseline [Ga-68]PSMA PET/MR with PET/MR after initiation (within 2-6 weeks) of therapy and evaluate if [Ga-68]PSMA is a suitable biomarker for treatment monitoring and assessment of early treatment response.

Secondary Objectives

• To compare early changes in PET biomarker ([Ga-68]PSMA) tumor uptake with treatment response assessed at completion of therapy (prediction of treatment response).
• To compare changes in MRI signal intensities (multi-parametric MRI) with treatment response assessed at completion of therapy.
• To compare results from multi-parametric MR imaging with [Ga-68]PSMA uptake.
• To assess combinations of quantitative PET and MRI metrics.

Study Design Patients, who enroll in this study, will undergo a baseline [Ga-68]PSMA PET/MR to assess the level of [Ga-68]PSMA tumor uptake. Patients with positive [Ga-68]PSMA tumor uptake (defined as [Ga-68]PSMA uptake twice the background activity) who are receiving systemic therapy will undergo a further [Ga-68]PSMA PET/MR 2-6 weeks after start of treatment. Patients with positive [Ga-68]PSMA tumor uptake will also be offered to participate in a test- retest study with a 2nd [Ga-68]PSMA PET/MR prior to treatment. Patients will therefore undergo a maximum of three [Ga-68]PSMA PET/MR imaging procedures. The first two test-retest Ga-PSMA-PET/MRI will be performed on separate days to allow for radioactive decay. There will be no other (e.g. clinically indicated) PET scan performed on the same day of [Ga-68]PSMA-PET/MRI.

• Study Type: Observational
• Enrollment (Actual): 8

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106-5065
      • University Hospitals, Case Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients diagnosed with tumors expressing PSMA including prostate cancer, breast cancer, lung cancer, renal cancer and other tumor types [Ga-68]PSMA PET/MRI known to express PSMA

Description

Inclusion Criteria:

• Patients with PSMA-positive tumors including prostate cancer, breast cancer, lung cancer, and other tumor types know to express PSMA
• Patients able to tolerate PET/MRI scans
• Informed consent must be given and signed

Exclusion Criteria:

• Subjects who do not meet the above mentioned inclusion criteria
• Subjects who refuse to give and/or sign the informed consent
• Patients who have a history of serious adverse events related to a previous MRI or PET/CT
• Patients who are unable to undergo MRI scanning due to exclusion by institutional MRI restriction policies as mentioned in the standard institutional MRI informed consent form
• Patients who are currently pregnant or breast feeding. A pregnancy test within 72 hours of the first PET/MRI will be performed.
• Anti-cancer treatment (chemotherapy and/or radiation therapy) within the last 2 weeks.
• Renal insufficiency: elevated Creatinine and/or Glomerular Filtration Rate (GFR)<40ml/min/1.7sqm (exclusion criterion only for contrast enhanced MRI)
• Patients with a known allergy against any component of the contrast enhancing MR agent will not receive MR contrast agents. (exclusion criterion only for contrast enhanced MRI)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
[Ga-68]PSMA PET/MR; Up to 3 experimental PET/MRI scans will be performed to determine the level of [Ga-68]PSMA tumor uptake	Device: [Ga-68]PSMA PET/MR; All participants will undergo at least 1 baseline [Ga-68]PSMA PET/MR. If participants test positive for [Ga-68]PSMA tumor uptake, they will under up to 2 additional scans; Other Names: PET/MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Test-retest reproducibility of PET biomarker ([Ga68]-PSMA) uptake using PET/MRI	The outcome measure for the statistical analysis of the test-retest reproducibility will be concordance analysis of standard uptake values (SUVs) between the 2 baseline scans	Up to 6 weeks after beginning treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Test-retest reproducibility of quantification of MRI sequences (multi-parametric MRI)	Morphologic imaging will be performed based on standard of care imaging protocols for anatomic detail and localization. Quantitative analysis will include Diffusion weighted imaging (DWI) and Dynamic contrast enhanced MRI (DCE-MRI)	Up to 6 weeks after beginning treatment
Ability of PET/MRI to measure changes in PET biomarker [Ga-68]PSMA) tumor uptake after initiation of therapy	A region of interest (ROI) will be placed in tumor lesions on the digital PET images in order to obtain Standardized Uptake Values (SUV) and/or time activity curves (TACs). Relative and absolute differences in tumor SUVs between pre-treatment PET vs. PET after initiation of therapy will be calculated. These differences in [Ga-68]PSMA tumor uptake will be compared with treatment response at completion of therapy (prediction of treatment response).	Up to 6 weeks after beginning treatment
Changes in MR signal intensities after initiation of therapy	Standard morphologic imaging will be obtained in a target area harboring tumor tissue before and after treatment. Quantitative parameters will be obtained in the respective techniques by drawing a region of interest (ROI) in the tumor lesions using dedicated post processing software and interactive workstations. Relative and absolute differences in tumor signal intensities and quantitative parameters will be calculated between pre-treatment PET vs. PET after initiation of therapy. These differences will be compared with treatment response at completion of therapy (prediction of treatment response) as assessed by standard of care imaging	Up to 6 weeks after beginning treatment
Comparison of early changes in PET biomarker ([Ga68]PSMA) tumor uptake with treatment response assessed at completion of therapy	Relative and absolute differences in tumor SUVs between pre-treatment PET vs. PET after initiation of therapy will be compared with treatment response at completion of therapy.	Up to 6 weeks after beginning treatment
Comparison of changes in MRI signal intensities (multi-parametric MRI) with treatment response assessed at completion of therapy	Relative and absolute differences in tumor MRI signal intensities and quantitative parameters as described above between pre-treatment PET vs. PET after initiation of therapy will be compared with treatment response at completion of therapy.	Up to 6 weeks after beginning treatment
Comparison of results from multi-parametric MR imaging with [Ga-68]PSMA tumor uptake	Changes of tumor Ga68-PSMA uptake between baseline and during treatment will be compared with changes in MR multiparametric imaging (e.g. apparent diffusion coefficient (ADC) maps, MR perfusion parameters, changes in T2* maps, etc.). The ability of each PET and MR parameter will be assessed for the ability to predict treatment response.	Up to 6 weeks after beginning treatment
Assessment of combinations of quantitative PET and MRI metrics	Investigators will assess combinations of quantitative PET and MRI metrics regarding their ability to characterize tumors and predict treatment response. Advanced feature extraction and pattern recognition methods will be used to find a combination of fused MRI and PET features that are correlated with disease signature.	Up to 6 weeks after beginning treatment

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Investigators: Principal Investigator: Norbert Avril, MD, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 14, 2018
• Primary Completion (ACTUAL): October 25, 2019
• Study Completion (ACTUAL): October 25, 2019

Study Registration Dates

• First Submitted: November 22, 2016
• First Submitted That Met QC Criteria: November 28, 2016
• First Posted (ESTIMATE): December 1, 2016

Study Record Updates

• Last Update Posted (ACTUAL): May 7, 2021
• Last Update Submitted That Met QC Criteria: May 5, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: PSMA; PET/MRI
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: CASE7Y16

Drug and device information, study documents

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