FAPI PET in Pleural Mesothelioma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Aalborg University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

Trial duration

29 Jan 2025 → ongoing

Decision date (initial)

2024-10-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

The Department of Nuclear Medicine, Aalborg University Hospital

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis

Investigate the diagnostic accuracy of FAPI in malignant pleural mesothelioma (PM) for primary staging.

Secondary objectives 10

1. Investigate the FAPI PET uptake parameters in suspicious PM lesions.
2. Explore the clinical role of FAPI PET in determining biopsy procedures of suspicious pleural PM lesions.
3. Explore potential limitations of FAPI PET in PM.
4. Explore the feasibility of FAPI PET for response assessment in PM.
5. Investigate FDG PET-based response assessment in PM.
6. Evaluate the prognostic value of FAPI PET/CT and FDG PET/CT in PM.
7. Investigate the level of FAP expression in different PM subtypes and its correlation with FAPI uptake in the PET images.
8. Correlate the FAPI and FDG uptake parameters in different PM subtypes.
9. Analyze changes in FAPI and FDG uptake parameters from before to after anticancer treatment.
10. Calculate the FAPI PET/CT interobserver agreement.

Conditions and MedDRA coding

Pleural Mesothelioma

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Patients with pleural lesions suspicious of pleural mesothelioma and referred to biopsy.
2. Undergone/undergoing FDG PET/CT as part of the diagnostic workup of a suspicious PM lesion
3. Considered physically and mentally able to participate in the research project
4. Understands the study subject information and able to consent to project participation
5. 18-years or older

Exclusion criteria 7

1. Patients with an imminent need for surgery or in an emergency
2. Known concurrent other malignancy with active treatment within the last 1 year; non-melanoma skin cancer and cervical cancer in situ are exempt
3. Pregnant or breastfeeding women
4. Fertile women not using effective contraceptives
5. Subjects unable to undergo PET/CT
6. History of allergic reactions / hypersensitivity attributed to [ 18F]FDG or FAPI-tracers
7. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Compare the FAPI PET/CT and FDG PET/CT findings in primary tumor, regional lymph nodes and distant metastases to a histopathological reference standard where the sensitivity, specificity, PPV, and NPV of the PET/CTs are determined at primary staging

Secondary endpoints 15

1. Calculate the proportion of patients where the location of the intended pleural biopsy is altered due to FAPI PET/CT replacing FDG PET/CT and other imaging modalities’ role in guiding the pleural biopsy. This will be determined at the tentative MDT.
2. Compare the cancer stage (IASCL 8 th edition TNM-classification) as determined by FAPI PET/CT compared to conventional imaging (including FDG PET/CT) at primary staging. The proportion of patients downstaged, unchanged stage, and upstaged, due to the added FAPI PET/CT are determined.
3. 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. The proportion of patients hypothetically treated differently, as deemed by collaborating clinicians participating in the tentative MDT, due to more advanced disease or less advanced disease, are determined.
4. Measure/calculate standardized uptake value (SUV) and tumor to background ratio (TBR) values for pleural PM lesions, regional lymph nodes, and distant metastases for FAPI PET/CT and compare these values to FDG PET, both at primary staging and after 2-3 series of anticancer treatment.
5. Measure/calculate FAPI PET SUV and TBR in benign pleural lesions, as revealed upon histopathology or composite reference standard, and compare these values to those derived from the primary FDG PET.
6. Calculate changes in SUV and TBR in primary, regional lymph nodes, and distant metastases for FAPI PET - from before to after 2-3 series of anticancer treatment and compare these values to the changes in the FDG PET parameters
7. Measure/calculate MITV (Molecular Imaging Tumor Volume) and VIP (Volume Intensity Product) for both FAPI PET/CT and FDG PET/CT at primary staging and after 2-3 series of anticancer treatment and compare these values between FAPI PET/CT and FDG PET/CT.
8. Calculate changes in MITV and VIP for both FAPI PET/CT and FDG PET/CT from before to after neoadjuvant chemotherapy and compare these values between FAPI PET/CT and FDG PET/CT.
9. Correlate the FAPI PET and FDG PET uptake parameters (SUV, TBR, MITV, VIP) to the subtype of PM (epithelioid, biphasic, sarcomatoid).
10. A 10 year follow up of included patients will be conducted to determine overall survival (OS), Recurrence Free Survival (RFS) and Progression Free Survival (PFS). These will be compared between FAPI PET/CT based markers (e.g., tentative FAPI PET stage, SUV, TBR, MITV, VIP) and other common clinical practice derived markers (e.g., FDG PET staging, other biomarkers).
11. 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.
12. Conduct an interobserver study of FAPI PET/CTs performed in the present and other future FAPI PET/CT cancer studies conducted at Aalborg UH.
13. 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.
14. Correlate the FAPI PET SUV to FAP targeting immunohistochemistry. Furthermore, FAP based volumedensity estimations pleural biopsies will be conducted and sought correlated with the FAPI PET SUV.
15. Report potential AEs and ARS related to the [68Ga]Ga-FAPI-46 injection.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Aalborg University Hospital

Sponsor organisation

Aalborg University Hospital

Address

Hobrovej 18-22

City

Aalborg

Postcode

9000

Country

Denmark

Scientific contact point

Organisation

Aalborg University Hospital

Contact name

Helle D. Zacho

Public contact point

Organisation

Aalborg University Hospital

Contact name

Helle D. Zacho

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications