The Diagnostic Accuracy and Clinical Value of FAPI PET in Pleural Mesothelioma

Phase 2

Recruiting

• Conditions: Pleural Mesothelioma; Pleural Diseases; Cancer; FAPI; Fibroblast Activation Protein Inhibitor
• Interventions: Drug: [68Ga]Ga-FAPI-46 PET/CT

• Registration Number: NCT06790082
• Lead Sponsor: Aalborg University Hospital

Brief Summary

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.

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 Timeline

• Status Verified: 2025-01
• Study First Submitted: 2025-01-10
• Study First Submitted QC: 2025-01-22
• Last Update Submitted: 2025-01-22
• Study First Posted: 2025-01-23
• Last Update Posted: 2025-01-23
• Study Start: 2025-01-25
• Primary Completion: 2027-04-30
• Study Completion: 2037-04-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 70

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Suspected pleural mesothelioma	[68Ga]Ga-FAPI-46 PET/CT	Patients with suspected pleural mesotheliom undergo an additional study specific \[68Ga\]Ga-FAPI-46 PET/CT at primary staging.

Primary Outcome Measures

Name	Time	Method
Diagnostic Performance	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.

Secondary Outcome Measures

Name	Time	Method
Location biopsy	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.
Staging	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.
Patient Management	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.
Uptake Values	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.
Changes uptake parameters due to anticancer treatment	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 %.
Correlate immunohistochemistry	5 years	Correlate the FAPI PET SUV to FAP targeting immunohistochemistry of biological material.
Incidental findings	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.
Safety Evaluation FAPI-injection	2.5 years	Report Incidence Treatment-Emergent Adverse Events
Overall survival	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.
Recurrence/Progression Free Survival	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.
Response evaluation	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.
Interobserver reliability	5 years	Conduct an interobserver study of FAPI PET/CTs. Cohens Kappa d will be calculated.

Trial Locations

Locations (1)

Aalborg University Hospital; 🇩🇰 Aalborg, Region North Jutland, Denmark