Clinical trial NCT06790082: The Diagnostic Accuracy and Clinical Value of FAPI PET in Pleural Mesothelioma
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Pleural Mesothelioma
Pleural Diseases
Cancer
FAPI
Fibroblast Activation Protein Inhibitor
Keywords: FAPI
68Ga-FAPI-46
PET/CT
Pleural Mesothelioma
FDG PET/CT
Lead sponsor: Aalborg University Hospital
Sponsor class: OTHER
First posted: 2025-01-23
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Diagnostic Performance
timeFrame: 2 years
Secondary outcomes:
measure: Location biopsy
timeFrame: 2 years
measure: Staging
timeFrame: 2 years
measure: Patient Management
timeFrame: 2 years
measure: Uptake Values
timeFrame: 2.5 years
measure: Changes uptake parameters due to anticancer treatment
timeFrame: 2.5 years
measure: Correlate immunohistochemistry
timeFrame: 5 years
measure: Incidental findings
timeFrame: 3 years
measure: Safety Evaluation FAPI-injection
timeFrame: 2.5 years
measure: Overall survival
timeFrame: 10 years
measure: Recurrence/Progression Free Survival
timeFrame: 10 years
measure: Response evaluation
timeFrame: 10 years
measure: Interobserver reliability
timeFrame: 5 years
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
state: Region North Jutland
Study officials:
affiliation: Clinical Professor dept. of Nuclear Medicine, Aalborg University Hospital
name: Helle Zacho, MD, DMSc
role: STUDY_DIRECTOR
References:
citation: Guglielmo P, Crivellaro C, Castello A, Della Corte CM, Pagano M, Marchesi S, Occhipinti M, Zucali PA, Evangelista L. Emerging Radiopharmaceuticals in Pet Imaging for Mesothelioma: A Review of [18F]FDG Alternatives. Mol Diagn Ther. 2025 Jan;29(1):55-66. doi: 10.1007/s40291-024-00756-4. Epub 2024 Nov 8.
citation: Guzel Y, Komek H, Can C, Kaplan I, Kepenek F, Ebinc S, Buyukdeniz MP, Gundogan C, Oruc Z. Comparison of the role of 18 F-fluorodeoxyglucose PET/computed tomography and 68 Ga-labeled FAP inhibitor-04 PET/CT in patients with malignant mesothelioma. Nucl Med Commun. 2023 Jul 1;44(7):631-639. doi: 10.1097/MNM.0000000000001702. Epub 2023 Apr 28.
citation: Kessler L, Schwaning F, Metzenmacher M, Pabst K, Siveke J, Trajkovic-Arsic M, Schaarschmidt B, Wiesweg M, Aigner C, Plones T, Darwiche K, Bolukbas S, Stuschke M, Umutlu L, Nader M, Theegarten D, Hamacher R, Eberhardt WEE, Schuler M, Herrmann K, Fendler WP, Hautzel H. Fibroblast Activation Protein-Directed Imaging Outperforms 18F-FDG PET/CT in Malignant Mesothelioma: A Prospective, Single-Center, Observational Trial. J Nucl Med. 2024 Aug 1;65(8):1188-1193. doi: 10.2967/jnumed.124.267473.