The Diagnostic Accuracy and Clinical Value of FAPI PET in Pleural Mesothelioma (FAPI-PM)

July 1, 2025 updated by: Morten Bentestuen, Aalborg University Hospital

FAPI PET in Pleural Mesothelioma: The Diagnostic Accuracy and Clinical Value of FAPI PET at Diagnosis, Primary Staging, and the Feasibility of FAPI PET for Response Evaluation

Seventy (N=70) patients with suspected pleural mesothelioma (PM) lesions referred to pleural biopsy will be recruited, and undergo an additional FAPI PET/CT at primary staging.

The FAPI PET/CT results will be compared to conventional imaging (including FDG PET/CT). The diagnostic accuracy will be determined with histopathology as reference standard.

For patients undergoing anticancer treatment (chemotherapy, immunotherapy, other treatment), an additional FAPI PET/CT and an additional FDG PET/CT will be conducted after the study subjects have completed 2-3 series of anticancer treatment. The feasabilitiy of FAPI PET/CT in response evaluation will be investigated.

All study specific analyzes will be blinded and will not influence the patient management / treatment.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

A new and promising PET tracer has been developed: Gallium-68 labelled fibroblast activation protein inhibitor (FAPI). FAPI binds to fibroblast activation protein (FAP), a type II transmembrane protein, which is expressed and upregulated in cancer associated fibroblasts. FAPI PET/CT has been superior to FDG PET/CT regarding tumor detection rate in multiple cancer entities. When evaluating the clinical value of FAPI PET/CT compared to conventional imaging, including FDG PET/CT, studies have shown that FAPI PET/CT led to a revised staging in up to 25-30% of cancer patients, and a revised treatment in up to 20-30% of patients. The clinical interest in FAPI extends beyond the use as a diagnostic tool, as the 68Ga-isotope can be replaced by a β-emitting isotope, e.g., 177-Lu or 90-Y, enabling radionuclide therapy of FAPI-avid cancers.

FAP-immunohistochemistry (FAP-IHC) studies in PM have shown promising results, and - as PM is of mesodermal origin, FAP-overexpression has been observed in the cancer cells themselves.

To date, only two clinical FAPI PET study in PM has been conducted. In these studies uptake values were significantly higher for FAPI PET compared to FDG PET regarding primary tumors and lymph node metastases. Moreover, FAPI PET/CT led to upstaging in some of the patients compared to FDG PET/CT.

Based on pathological studies, implementation of FAPI PET/CT could be particularly beneficial in sarcomatoid and biphasic PM subtypes, which are characterized by aggressive growth and a worse prognosis compared to the epithelioid subtypes, however, non-epithelioid subtypes are underrepresented in FAPI PET studies to date.

PM in most cases is diagnosed at advanced stages of the disease and surgery with pleurectomy/decortication is only indicated in select cases with localized disease (approx. 30% of patients with the epithelioid subtype). Therefore, most patients undergo palliative treatment with either chemotherapy, immunotherapy, or radiotherapy. Considering the inherent limitations and difficulties for CT based response evaluation tools in PM, experts argue that response assessment using FDG PET/CT, i.e., PET Response Evaluation Criteria in Solid Tumors (PERCIST), could be an even more sensitive tool in PM compared to anatomical imaging response tools.

To date, there are no studies evaluating the feasibility of FAPI PET for response assessment in PM.

The study is a prospective explorative study complying with the Standard for Reporting Diagnostic Accuracy (STARD) criteria where 70 patients with suspected PM are recruited.

An additional FAPI PET/CT will be performed as a study specific procedure at primary staging within 4 weeks of the primary staging FDG PET/CT and prior to the pleural biopsy. All included study subjects will undergo this additional primary staging FAPI PET/CT. Patients with benign histology will not receive any further study related procedures - unless they are re-recruited at a later time point. For the proportion of study subjects treated with chemotherapy or immunotherapy (anticancer treatment), as part of common clinical practice, additional study specific FAPI PET/CT and FDG PET/CT will be conducted after completing 2-3 series of anticancer treatment, that is 3 series of chemotherapy or 2 series of immunotherapy.

The study specific procedures will be conducted in addition to common clinical practice and will not interfere with or delay the routine diagnostic workup or treatment. The results of the study specific procedures will not be available to the patient or the treating physicians (blinded) and will not interfere with planned treatment/diagnostics.

Study Type

Interventional

Enrollment (Estimated)

70

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Denmark
    • Region North Jutland
      • Aalborg, Region North Jutland, Denmark, 9000
        • Recruiting
        • Aalborg University Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with pleural lesions suspicious of pleural mesothelioma and referred to pleural biopsy.
  • Undergone/undergoing FDG PET/CT as part of the diagnostic workup of a suspicious PM lesion.
  • Considered physically and mentally able to participate in the research project.
  • Understands the study subject information and able to consent to project participation.
  • 18-years or older

Exclusion Criteria:

  • Patients with an imminent need for surgery or in an emergency
  • Known concurrent other malignancy with active treatment within the last 1 year; non-melanoma skin cancer and cervical cancer in situ are exempt.
  • Pregnant or breastfeeding women.
  • Fertile women (women of childbearing potential) who could - theoretically - be pregnant (i.e., unknown pregnancy status).

Fertile women will be tested for pregnancy (by urine humane choriogonadotropin (HCG) or serum HCG) within 48h before FAPI PET/CTs, both at primary staging and restaging. Study subjects can participate in the study if the pregnancy test is negative (i.e., not pregnant).

  • Subjects unable to undergo PET/CT: e.g., weighing more than 180 kg (weight limit scanner), unable to fit within the imaging gantry, inability to remain still for the duration of the examination, or with known severe claustrophobia unresponsive to oral anxiolytics or severe fear of needles.
  • Subjects with any medical condition or other circumstances that, in the opinion of the Investigator, would significantly decrease the reliability of data, achievement of study objectives or completing the study.
  • History of allergic reactions / hypersensitivity attributed to [18F]FDG or FAPI-tracers.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Suspected pleural mesothelioma
Patients with suspected pleural mesotheliom undergo an additional study specific [68Ga]Ga-FAPI-46 PET/CT at primary staging.
Drug: [68Ga]Ga-FAPI-46 PET/CT

Patients with suspected pleural mesothelioma undergo FAPI PET/CT in addition to conventional imaging at primary staging.

The subgroup of patients undergoing anticancer treatment will undergo an additional FAPI PET/CT and FDG PET/CT after completing 2-3 series of anticancer treatment.

Other Names:
  • [68Ga]Gallium - Fibroblast Activation Protein Inhibitor-46 Positron Emission Tomography / Computer Tomography

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diagnostic Performance
Time Frame: 2 years
The diagnostic performance (sensitivity, specificity, positive predicative value, negative predicative value, and overall diagnostic accuracy - all parameters in %). in of FAPI PET compared to routine imaging modalities, including FDG PET/CT, in suspected PM lesions.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Location biopsy
Time Frame: 2 years
Calculate the proportion of patients where the location of the intended pleural biopsy is altered due to FAPI PET/CT replacing FDG PET/CT.
2 years
Staging
Time Frame: 2 years
Compare the cancer stage (IASCL 9th edition TNM-classification) as determined by FAPI PET/CT compared to conventional imaging (including FDG PET/CT) at primary staging.
2 years
Patient Management
Time Frame: 2 years
Calculate the proportion of patients with suspected PM lesion with a change in treatment following the -hypothetical - addition of FAPI PET/CT at primary staging.
2 years
Uptake Values
Time Frame: 2.5 years
Investigate the FAPI PET uptake parameters in suspicious PM lesions (primary tumor), regional lymph nodes, and distant metastases, and in benign lesions. Correlate FAPI uptake parameters in different PM sutypes.
2.5 years
Changes uptake parameters due to anticancer treatment
Time Frame: 2.5 years
Calculate changes in FAPI PET uptake parameters - from before to after 2-3 series of anticancer treatment. Changes will be presented as ratios and in %.
2.5 years
Correlate immunohistochemistry
Time Frame: 5 years
Correlate the FAPI PET SUV to FAP targeting immunohistochemistry of biological material.
5 years
Incidental findings
Time Frame: 3 years
Seek supplementary information in medical records, biochemistry, pathology, or other imaging modalities for a final diagnosis/condition in cases of unexpected FAPI PET/CT findings.
3 years
Safety Evaluation FAPI-injection
Time Frame: 2.5 years
Report Incidence Treatment-Emergent Adverse Events
2.5 years
Overall survival
Time Frame: 10 years
A 10 year follow up of included patients will be conducted to determine overall survival (OS) in days from diagnosis, correlated to FAPI PET/CT results.
10 years
Recurrence/Progression Free Survival
Time Frame: 10 years
A 10 year follow up of included patients will be conducted to determine Recurrence Free Survival (RFS) and Progression Free Survival (PFS) in days from diagnosis, correlated to FAPI PET/CT results.
10 years
Response evaluation
Time Frame: 10 years
Compare conventional CT-based response assessment (mRECIST/iRECIST) to PET based response assessment (PERCIST, and other FDG and FAPI PET derived data) to the clinical outcome, i.e., OS, RFS/PFS.
10 years
Interobserver reliability
Time Frame: 5 years
Conduct an interobserver study of FAPI PET/CTs. Cohens Kappa d will be calculated.
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Aalborg University Hospital

Investigators

  • Study Director: Helle Zacho, MD, DMSc, Clinical Professor dept. of Nuclear Medicine, Aalborg University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 29, 2025

Primary Completion (Estimated)

April 30, 2027

Study Completion (Estimated)

April 30, 2037

Study Registration Dates

First Submitted

January 10, 2025

First Submitted That Met QC Criteria

January 22, 2025

First Posted (Actual)

January 23, 2025

Study Record Updates

Last Update Posted (Actual)

July 3, 2025

Last Update Submitted That Met QC Criteria

July 1, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EU CT: 2024-514301-62-00
  • 2024-514301-62-00 (Ctis)

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

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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