FAPI-74 PET/CT in Adults With Fibrosis

Fibroblast Activating Protein (FAP) PET/CT in Adults With Fibrotic Conditions

This protocol is intended as a basket protocol designed to evaluate the use of Fibroblast Activating Protein (FAP) PET/CT in imaging the presence of fibrosis caused by a variety of medical conditions where fibrosis is believed to lead to pathological effects and poor prognosis.

Study Overview

• Status: Not yet recruiting
• Conditions: Fibrosis (Morphologic Abnormality)
• Intervention / Treatment: Drug: [F-18]-FAPI-74

Detailed Description

A study to evaluate subjects with fibrosis-inducing medical conditions that are known or suspected to cause tissue fibrosis (e.g. cancer-associated, post-infection, post-radiation, pre or post-transplant, cardiac, liver, kidney or pulmonary fibrosis). This protocol is intended to expand as needed with imaging arms designed to evaluate the use of Fibroblast Activating Protein (FAP) PET/ CT in imaging the presence fibrosis caused by medical conditions where fibrosis is believed to lead to pathological effects and poor prognosis.

[18F]-FAPI-74 is a positron emitting radiolabeled FAP inhibitor that will be used with a positron emission tomography/computed tomography (PET/CT) scan that will be completed in each subject who has a clinical suspicion of fibrotic disease.

PET/CT imaging will be used to evaluate the distribution of fibroblast activating protein (FAP) in major organs and other tissues affected with fibrotic diseases or conditions. This is an observational study in that [F-18]-FAPI-74 PET/CT will not be used to direct treatment decisions. While patients and referring physicians will not be blinded to the [F-18]-FAPI-74 PET/CT results, any medical or treatment decisions related to their underlying clinical diagnosis will be made by the treating physicians based upon clinical criteria.

After injection of [F-18]-FAPI-74, patients will undergo a vertex to mid-thigh scan, starting at approximately 60 minutes post injection. PET/CT imaging sessions will include an injection of approximately 8.0 mCi (expected range of doses is expected to be 6.0-8.0 mCi) of [F-18]-FAPI-74 intravenously. Data will be collected to evaluate uptake of [F-18]-FAPI-74 in sites of suspected fibrosis and in major organs.

An optional second PET/CT using [F-18]-FAPI-74 can be considered at the request of the investigators at any clinically relevant time point. This second scan may be used to quantify the changes in fibrosis over time as part of the natural progression of the fibrotic condition, or to observe changes in [F-18]- FAPI-74 uptake in response to therapeutic interventions.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Erin Schubert; Phone Number: 215-573-6569; Email: erinschu@pennmedicine.upenn.edu
• Study Contact Backup: Name: Mary Hansbury; Phone Number: 215-746-8192; Email: mary.hansbury@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
      • Contact: Erin Schubert; Phone Number: 215-573-6569; Email: erinshu@pennmedicine.upenn.edu
      • Contact: Mark A Sellymer, MD, PhD; Email: mark.sellymer@pennmedicine.upenn.edu
      • Principal Investigator: Mark A Sellmyer, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Head and Neck Cancer Cohort:

1. Participants will be ≥ 21 years of age
2. Diagnosis of oropharyngeal squamous cell carcinoma (OPSCC)
3. Determined to be surgical candidates

PTLD Cohort:

1. Participants will be ≥ 21 years of age
2. Diagnosed with microbiologically confirmed DS-pTB (culture positive)
3. Completed DS-pTB treatment according to IDSA guidelines in the past 3 months to 2 years
4. Negative test for sputum Mtb culture at least two consecutive times during TB treatment without a subsequent positive Mtb culture (indicating cure as per CDC guidelines)

All Cohorts:

1. History of known or suspected fibrosis-inducing medical condition
2. Participants must be informed of the investigational nature of this study and be willing to provide written informed consent and participate in this study in accordance with institutional and federal guidelines prior to study-specific procedures.

Exclusion Criteria:

Head and Neck Cancer Cohort:

1. Participant is not eligible for tissue resection

PTLD Cohort:

1. Diagnosed with TB that is resistant to rifampin
2. History of alternative pulmonary disease
3. Have been administered corticosteroids or any other systemic investigational agents within 3 months of screening
4. Have symptoms or signs suggestive of active TB at the time of screening

All Cohorts:

1. Women of childbearing potential may not be pregnant or breastfeeding. A negative pregnancy test will be required before [F-18]- FAPI-74injection.
2. Inability to tolerate imaging procedures in the opinion of an investigator or treating physician
3. Any current medical condition, illness, or disorder as assessed by medical record review and/or self-reported that is considered by a physician investigator to be a condition that could compromise participant safety or successful participation in the study
4. Treatment with a therapeutic agent targeting fibroblast activation protein (FAP) within 1 month prior to study enrollment.

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: FAPI-74 PET/CT Scan; Head and neck cancer (up to 5 subjects), post tubercular lung disease (PTLD, up to 10 subjects) and exploratory (up to 10 subjects) with fibrosis-inducing medical conditions that are known or suspected to cause tissue fibrosis (e.g. cancer-associated, postinfection, post-radiation, pre/post-transplant, cardiac, liver, kidney or pulmonary fibrosis).

Drug: [F-18]-FAPI-74; A positron-emitting radiopharmaceutical that has been studied in animals for selective measurement of the in vivo expression of FAP with positron emission tomography (PET/CT).; Other Names: [18F] aluminium fluorine ((S)-2,2'(7- (2-(4-(3-(4-(2-(2- cyanopyrrolidin-1-yl)-2 oxoethylcarbamoyl)quinolin-6-yloxy) propyl)piperazin-1-yl)-2-oxoethyl)-1,4,7- triazonane-1,4-diyl)diacetic acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall FAPI-74 PET/CT Image Analysis	The overall quality of the generated images will be evaluated. Initial imaging of the vertex to mid-thigh will be used to investigate regional tracer uptake in suspected sites of fibrosis and normal tissues for this novel radiotracer. Uptake and retention of [F-18]-FAPI-74 in known or suspected sites of fibrotic disease will be evaluated visually by trained radiology readers, the principal investigator, or designee. A number of analysis methods may be tested to identify the optimal method for analyses for future studies with this radiotracer. [F-18]-FAPI-74 PET/CT scans will be interpreted both qualitatively and quantitatively.	3 years
Head and Neck Cancer FAPI-74 PET/CT Image Analysis	[18F]-FAPi74 PET/CT data: Areas of uptake in tumors and healthy tissue will be measured by SUVmax and semiquantitative analysis will be conducted. In each case, lesion uptake will be marked as low, medium, and high avidity. Each lesion and lymph node will be separately measured and quantified. Measurements will be made by Dr. Sellmyer and co-Investigators (n=3).	3 years
PTLD FAPI-74 PET/CT Image Analysis	Quantitative interpretation of FAP expression, will be recorded as a Standardized Uptake Value (SUV). Max, mean, and peak SUV values will be recorded for a region-of-interest encompassing a single primary lesion.	3 years

Collaborators and Investigators

• Sponsor: Abramson Cancer Center at Penn Medicine
• Investigators: Principal Investigator: Mark A Sellmyer, MD, PhD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Estimated): May 30, 2024
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): May 30, 2027

Study Registration Dates

• First Submitted: May 9, 2024
• First Submitted That Met QC Criteria: May 9, 2024
• First Posted (Actual): May 14, 2024

Study Record Updates

• Last Update Posted (Actual): May 14, 2024
• Last Update Submitted That Met QC Criteria: May 9, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Fibrosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiparasitic Agents; Antinematodal Agents; Anthelmintics; Mebendazole; Piperazine; Piperazine citrate; DMP 777
• Other Study ID Numbers: 19923

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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