Immune Checkpoint Blockade Therapy Using 18F-FLT PET/CT

Early Assessment of Response to Immune Checkpoint Blockade Therapy Using 18F-FLT PET/CT

In the current study, advanced positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance (PET/MR) imaging methods will be used to validate the hypothesis that participants receiving immune checkpoint blockade (ICB) therapy, who ultimately achieve clinical benefit, will show an increase, or "FLARE", in tumor FLT and/or FDG uptake from baseline, as seen after cycle#1 of treatment, and that after 2 cycles of treatment responders will have a decline in FLT and FDG uptake, in comparison to the participants classified as "non-responders".

Study Overview

• Status: Recruiting
• Conditions: Cancer
• Intervention / Treatment: Device: FDG PET/CT; Device: FLT PET/CT; Device: PET/MR; Drug: [F-18] flurothymidine

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Richard L Wahl, M.D.; Phone Number: 314-362-7100; Email: rwahl@wustl.edu

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Sub-Investigator: Farrokh Dehdashti, M.D.
      • Contact: Richard L Wahl, M.D.; Phone Number: 314-362-7100; Email: rwahl@wustl.edu
      • Principal Investigator: Richard L Wahl, M.D.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed diagnosis of cancer.
• Patients who are planned to receive checkpoint blockade therapy, per referring oncologist.
• Life expectancy ≥ 6 months and < 5 years.
• Disease that is measurable per RECIST 1.1.
• Age ≥18 years.
• Ability and willingness to provide informed consent
• Women of child-bearing potential must have a negative urinary or serum pregnancy test within 7 days of each imaging time point.

Exclusion Criteria:

• Patient receiving other investigational radiotracers within 14 days prior to FLT and FDG imaging time points.
• Patients receiving ICB in combination with chemotherapy.
• Immunosuppressive therapy including systemic corticosteroids except for maintenance dosing for adrenal insufficiency. Patients requiring immunosuppressive therapy during the study will no longer be eligible.
• Known additional malignancy that is progressing or requires active treatment with the exceptions of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, autoimmune diseases, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients with a pacemaker, stainless steel aneurysm clip or any other magnetic resonance (MR) contraindicated implant or foreign body would warrant exclusion from this study. Pacemakers may be reprogrammed or turned off by the strong MRI magnetic field. Radio-frequency (RF) fields in MR can also cause severe heating of pacemaker lead tips. Steel aneurysm clips are prone to torque in the strong MR field which can displace the clips and may damage the vessel, resulting in hemorrhage, and/or death.
• Pregnant women are excluded from this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• 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: PET/CT + PET/MR; -Eligible patients will have imaging assessments (as part of the study) performed at three time-points: pre-treatment, following cycle 1 of treatment, and following cycle 2 of treatment. Baseline FDG PET/CT will be a standard-of-care procedure. If possible, PET/CT imaging will be performed, followed immediately by PET/MR imaging during each imaging session. At minimum, PET/MR should be obtained at least once during each time-point (i.e. either during the FDG or FLT procedure). FDG imaging and FLT imaging should be performed at least 24 hours apart and no more than 7 days apart.

Device: FDG PET/CT; A single dose of 10 mCi FDG will be given by bolus injection approximately 60 minutes prior to the first planned imaging procedure.; Device: FLT PET/CT; . A single dose of 10 mCi FLT will be given by bolus injection approximately 80 minutes prior to the first planned imaging procedure.; Device: PET/MR; MR imaging will be performed on a Siemens Biograph mMR or an MRI scanner, if the PET/MR is unavailable.; Drug: [F-18] flurothymidine; -Radiopharmaceutical

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in FLT uptake	Participants will be designated as responders or non-responders based on follow-up RECIST 1.1 measurements; Changes in FLT uptake will be compared between the two groups	Between pre-treatment PET/CT imaging and end of cycle 1 PET/CT imaging (estimated to be 1 month)
Change in FLT uptake	Participants will be designated as responders or non-responders based on follow-up RECIST 1.1 measurements; Changes in FLT uptake will be compared between the two groups	Between pre-treatment PET/CT imaging and end of cycle 2 PET/CT imaging (estimated to be 2 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in FDG uptake	Participants will be designated as responders or non-responders based on follow-up RECIST 1.1 measurements; Changes in FDG uptake will be compared between the two groups	Between pre-treatment PET/CT imaging and end of cycle 1 PET/CT imaging (estimated to be 1 month)
Change in FDG uptake	Participants will be designated as responders or non-responders based on follow-up RECIST 1.1 measurements; Changes in FDG uptake will be compared between the two groups	Between pre-treatment PET/CT imaging and end of cycle 2 PET/CT imaging (estimated to be 2 months)
Change in apparent diffusion coefficient (ADC) on diffusion-weighted MRI (DW-MRI)		From baseline to the end of second cycle of treatment (estimated to be 2 months)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Richard L Wahl, M.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2021
• Primary Completion (Estimated): January 31, 2025
• Study Completion (Estimated): January 31, 2025

Study Registration Dates

• First Submitted: February 12, 2020
• First Submitted That Met QC Criteria: February 12, 2020
• First Posted (Actual): February 17, 2020

Study Record Updates

• Last Update Posted (Actual): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 201909060

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data may be shared with other researchers. The researchers may be doing research at Washington University, at other research centers and institutions, or industry sponsors of research. Data may also be shared with large data repositories. The researchers may be doing research in areas similar to this research or in other unrelated areas.
• IPD Sharing Time Frame: Beginning 3 months and ending 10 years following article publication.
• IPD Sharing Access Criteria: Proposals should be submitted directly to rwahl@wustl.edu.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

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