Multicenter Validation Trial of [18F]AlF-FAPI-74 for PET Imaging of Cancer-associated Fibroblasts Through Fibroblast Activation Protein Inhibitors (FAPI) in Different Tumor Types (FAPIDO)

The aim of the project is to demonstrate superior detection ratio of [18F]AlF-FAPI-74 PET/CT compared to [18F]FDG PET/CT or conventional imaging in treatment-naïve, newly diagnosed patients with oesophagogastric adenocarcinoma (clinical T1-4N0-3M0) and pancreatic ductal adenocarcinoma (clinical T1-4N0-2M0-1) and describe the clinical utility of [18F]AlF-FAPI-74 PET/CT in oncological patients with a clinically challenging situation.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer; Pancreatic Ductal Adenocarcinoma; Oncologic Disorders; Oncology; Oesophageal Cancer; FAP
• Intervention / Treatment: Diagnostic test: [18F]AlF-FAPI-74 PET/CT

• Study Type: Interventional
• Enrollment (Estimated): 109
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • Not yet recruiting
    • University Hospital Antwerp (UZA)
    • Contact: Sigrid Stroobants, Prof. Dr.
  • Gent, Belgium, 9000
    • Recruiting
    • University Hospital Ghent
    • Contact: Karen Geboes, Prof. Dr.
    • Contact: Karen Geboes, Prof. Dr.; Phone Number: +32 9 332 05 30; Email: hiruz@uzgent.be
  • Leuven, Belgium, 3000
    • Recruiting
    • UZ Leuven
    • Contact: Christophe Deroose, Prof. Dr.; Phone Number: +3216343715; Email: christophe.deroose@uzleuven.be
    • Contact: Christophe Deroose, Prof. Dr.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria OGA:

1. Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures.
2. Age 18 or older.
3. New histologic or cytologic proven diagnosis of oesophagogastric adenocarcinoma.
4. Patient underwent a [18F]FDG PET/CT.
5. TNM classification: cT1-4N0-3M0

Inclusion Criteria PDAC:

1. Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures.
2. Age 18 or older.
3. New histologic or cytologic proven diagnosis of pancreatic ductal adenocarcinoma.
4. Patient underwent a [18F]FDG PET/CT or conventional staging with CT or MRI.
5. TNM classification: cT1-4N0-2M0-1, with the exception of upfront resectable patients.

Inclusion Criteria Clinically challenging cohort:

1. Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures.
2. Age 18 or older.
3. Histologic or cytologic proven diagnosis of a malignancy.
4. Patient underwent a [18F]FDG PET/CT.
5. Unexplained symptoms, complaints, biochemical or imaging (scintigraphy, PET, CT, MR) findings.

Exclusion Criteria:

1. Participant is mentally or legally incapacitated, doesn't understand the study design or is not willing or capable to undergo all study-specific procedures.
2. Any disorder or condition, which in the Investigator's opinion might jeopardise the participant's safety or compliance with the protocol.
3. Any prior or concomitant treatment(s) that might jeopardise the participant's safety or that would compromise the integrity of the Trial.
4. Female who is pregnant (urinary hCG test can be performed in case of doubt), breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate, highly effective contraceptive (with a relatively high Pearl Index: natural methods, minipill outside postpartum period, spermicides or condoms in monotherapy or no usage of contraception when sexually active are not accepted).
5. Participation in an interventional Trial with an investigational medicinal product (IMP) or device when the trial designs are not considered compatible by the study team.
6. Participation in a clinical scientific study in the last 12 months with a radiation exposure caused by the experimental procedures greater than 1 mSv.
7. Participant has a known hypersensitivity to [18F]AlF-FAPI-74 or the used excipients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oesophagogastric adenocarcinoma (OGA)	Diagnostic test: [18F]AlF-FAPI-74 PET/CT; A [18F]AlF-FAPI-74 PET/CT will be performed at the same site of the screening visit (UZ Leuven, UZ Gent or UZ Antwerpen). Subjects are required to be sober four hours before the scan. The patient will get an IV line, through which the [18F]AlF-FAPI-74 will be injected in one bolus (3,5 MBq/kg). After 60 minutes, the acquisition on the PET/CT scan will take place. The CT will be a low dose CT with oral contrast. After the scan, participants will be observed at the department in case of adverse events. During this time, the participant can fill in the PRO. The estimated duration of this visit is three hours. If the patient receives neo-adjuvant therapy, a second [18F]AlF-FAPI-74 PET/CT will be performed maximum one month before surgery. If the planned surgery gets postponed after the second [18F]AlF-FAPI-74 PET/CT has been performed, we will have the possibility to perform one additional (i.e. third) [18F]AlF-FAPI-74 PET/CT, before the final surgery.
Experimental: Pancreatic ductal adenocarcinoma (PDAC)	Diagnostic test: [18F]AlF-FAPI-74 PET/CT; A [18F]AlF-FAPI-74 PET/CT will be performed at the same site of the screening visit (UZ Leuven, UZ Gent or UZ Antwerpen). Subjects are required to be sober four hours before the scan. The patient will get an IV line, through which the [18F]AlF-FAPI-74 will be injected in one bolus (3,5 MBq/kg). After 60 minutes, the acquisition on the PET/CT scan will take place. The CT will be a low dose CT with oral contrast. After the scan, participants will be observed at the department in case of adverse events. During this time, the participant can fill in the PRO. The estimated duration of this visit is three hours. If the patient receives neo-adjuvant therapy, a second [18F]AlF-FAPI-74 PET/CT will be performed maximum one month before surgery. If the planned surgery gets postponed after the second [18F]AlF-FAPI-74 PET/CT has been performed, we will have the possibility to perform one additional (i.e. third) [18F]AlF-FAPI-74 PET/CT, before the final surgery.
Experimental: Clinically challenging situations	Diagnostic test: [18F]AlF-FAPI-74 PET/CT; A [18F]AlF-FAPI-74 PET/CT will be performed at the same site of the screening visit (UZ Leuven, UZ Gent or UZ Antwerpen). Subjects are required to be sober four hours before the scan. The patient will get an IV line, through which the [18F]AlF-FAPI-74 will be injected in one bolus (3,5 MBq/kg). After 60 minutes, the acquisition on the PET/CT scan will take place. The CT will be a low dose CT with oral contrast. After the scan, participants will be observed at the department in case of adverse events. During this time, the participant can fill in the PRO. The estimated duration of this visit is three hours. If the patient receives neo-adjuvant therapy, a second [18F]AlF-FAPI-74 PET/CT will be performed maximum one month before surgery. If the planned surgery gets postponed after the second [18F]AlF-FAPI-74 PET/CT has been performed, we will have the possibility to perform one additional (i.e. third) [18F]AlF-FAPI-74 PET/CT, before the final surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Objective OGA: demonstrate superiority of [18F]AlF-FAPI-74 PET/CT over [18F]FDG PET/CT.	Detection ratio for lymph node and distant metastases (combined).	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
Primary Objective PDAC: demonstrate superiority of [18F]AlF-FAPI-74 PET/CT over conventional imaging (CT or MRI) or [18F]FDG PET/CT (if available)	Detection ratio for lymph node and distant metastases (combined).	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
Primary Objective Clinically Challenging Situation: demonstrate contribution of [18F]AlF-FAPI-74 PET/CT in this setting.	Fraction of patients were scan was deemed contributory. This means: [18F]AlF-FAPI-74 identifies a lesion as malignant (true positive) with effective upstaging.; [18F]AlF-FAPI-74 identifies a lesion as non-malignant (true negative) with effective downstaging.; [18F]AlF-FAPI-74 can differentiate between a malignant or non-malignant lesion when there is doubt.; Other implications that are deemed contributory by the treating physician.	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OGA & PDAC: Detection ratio for tumor detection	primary tumor alone; lymph nodes alone (N-staging); distant metastases alone (M-staging) and lymph node + distant metastases combined (with inclusion of patients without N- or M-lesions).	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
OGA & PDAC: specificity, positive and negative predictive value and accuracy	Specificity, positive predictive value, negative predictive value, accuracy for lymph node and distant metastases (combined); for detection of primary tumor; for lymph nodes alone (N-staging); for distant metastases alone (M-staging).	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
OGA & PDAC: positive and negative likelihood ratios; diagnostic odds ratio.	Positive and negative likelihood ratios; diagnostic odds ratio.	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
OGA & PDAC: semi-quantitative uptake measurements	Semi-quantitative uptake measurements (maximal standardized uptake value (SUVmax), average SUV (SUVmean), peak SUV (SUVpeak) of tumoral lesions on [18F]AlF-FAPI-74 PET/CT and [18F]FDG PET/CT.	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
OGA & PDAC: tumor-to-background uptake values	Tumor-to-background uptake values (TBR; SUV lesion divided by SUV background) for [18F]AlF-FAPI-74 PET/CT and [18F]FDG PET/CT, using following background organs: liver, lung, gluteus muscle, mediastinal bloodpool, bowel, bone marrow (L4 if no abnormal uptake).	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
OGA & PDAC: impact on TNM stage	Impact on TNM stage of [18F]AlF-FAPI-74 PET/CT compared to full staging ([18F]FDG PET/CT and conventional imaging) and impact of [18F]AlF-FAPI-74 PET/CT compared to only conventional imaging-based staging.	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
OGA & PDAC: impact on clinical management	Impact on clinical management.	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
OGA & PDAC: impact on potential radiation therapy plan	Impact on potential radiation therapy plan.	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
OGA & PDAC: psychological impact	Psychological impact on patient of [18F]AlF-FAPI-74 PET/CT procedure.	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
OGA & PDAC: reproducibility	Intra- and interobserver reproducibility of both [18F]FDG and [18F]AlF-FAPI-74 PET/CT.	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
OGA & PDAC: adverse events	Patient safety: adverse events of [18F]AlF-FAPI-74 PET/CT.	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
OGA & PDAC: evolution between baseline and end of neo-adjuvant treatment	Evolution between baseline and end of neo-adjuvant treatment in patients with 2 [18F]AlF-FAPI-74 scans: (i) number of lesion; (ii) uptake; (iii) TBR; (iv) TNM score;(v) treatment plan based on scan.	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
OGA & PDAC: correlation with immunohistochemistry	Correlation of [18F]AlF-FAPI-74 biodistribution with FAP tissue expression as measured by immunohistochemistry (IHC).	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
Subgroup analysis OGA: lymph node detection	Subgroup 1: Upfront resectable patients. Subgroup 2: Patients scheduled for neo-adjuvant therapy (mostly classified as locally advanced). Sensitivity, specificity, postivie predictive value, negative predictive value for lymph nodes.	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
Subgroup analysis OGA: impact on TNM stage	Subgroup 1: Upfront resectable patients. Subgroup 2: Patients scheduled for neo-adjuvant therapy (mostly classified as locally advanced). Impact on TNM stage of [18F]AlF-FAPI-74 PET/CT compared to [18F]FDG PET/CT-based stage.	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
Subgroup analysis OGA: evolution between baseline and end of neo-adjuvant treatment	Subgroup 2: Patients scheduled for neo-adjuvant therapy (mostly classified as locally advanced). Evolution between baseline and end of neo-adjuvant treatment in patients with 2 [18F]AlF-FAPI-74 scans: (i) number of lesion; (ii) uptake; (iii) TBR; (iv) TNM score; (v) treatment plan based on scan	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
Subgroup analysis OGA: correlation with pathology	Subgroup 2: Patients scheduled for neo-adjuvant therapy (mostly classified as locally advanced). Correlation of imaging parameters and their change with pathological assessment of resection specimen (pTNM stage, regression grade).	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
Subgroup analysis PDAC: tumor detection	Subgroup 1: Patients scheduled for neo-adjuvant therapy (mostly classified as borderline resectable or locally advanced). Subgroup 2: Metastatic patients. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy for lymph nodes and distant metastases.	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
Subgroup analysis PDAC: impact on TNM stage	Subgroup 1: Patients scheduled for neo-adjuvant therapy (mostly classified as borderline resectable or locally advanced). Subgroup 2: Metastatic patients. Impact on TNM stage of [18F]AlF-FAPI-74 PET/CT compared to [18F]FDG PET/CT, CT or MRI-based stage.	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
Subgroup analysis PDAC: evolution between baseline and end of neo-adjuvant treatment	Subgroup 1: Patients scheduled for neo-adjuvant therapy (mostly classified as borderline resectable or locally advanced). Evolution between baseline and end of neo-adjuvant treatment in patients with 2 [18F]AlF-FAPI-74 scans: (i) number of lesion; (ii) uptake; (iii) TBR; (iv) TNM score; (v) treatment plan based on scan	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
Subgroup analysis PDAC: correlation with pathology	Subgroup 1: Patients scheduled for neo-adjuvant therapy (mostly classified as borderline resectable or locally advanced). Correlation of imaging parameters and their change with pathological assessment of resection specimen (pTNM stage, regression grade).	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
Subgroup analysis PDAC: association with survival	Subgroup 2: Metastatic patients. Association between total tumor burden on [18F]AlF-FAPI-74 PET/CT and survival. Association between semi-quantitative uptake measurements (maximal standardized uptake value (SUVmax), average SUV (SUVmean), peak SUV (SUVpeak) of tumoral lesions on [18F]AlF-FAPI-74 PET/CT and survival.	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
Clinically Challenging Situation: detection rate	Primary tumor/local recurrence, lymph node and distant metastases detection rate (compared to best value comparator) vs. [18F]FDG PET/CT.	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
Clinically Challenging Situation: semi-quantitative uptake measurements	Semi-quantitative uptake measurements (maximal standardized uptake value (SUVmax), average SUV. (SUVmean), peak SUV (SUVpeak)) of tumoral lesions on [18F]AlF-FAPI-74 PET/CT and [18F]FDG PET/CT	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
Clinically Challenging Situation: tumor-to-background uptake values	Tumor-to-background uptake values (SUV lesion divided by SUV background) on [18F]AlF-FAPI-74 PET/CT and [18F]FDG PET/CT, using following background organs: liver, lung, gluteus muscle, mediastinal bloodpool, bowel, bone marrow (L4 if no abnormal uptake).	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
Clinically Challenging Situation: impact on potential radiation therapy plan	Impact on potential radiation therapy plan of [18F]AlF-FAPI-74 PET/CT vs. [18F]FDG PET/CT.	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
Clinically Challenging Situation: reproducibility	Intra- and interobserver reproducibility.	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)
Clinically Challenging Situation: adverse events	Patient safety: adverse events.	From enrollment to the end of the follow-up period (i.e. 12 months after first [18F]AlF-FAPI-74 PET/CT)

Collaborators and Investigators

• Sponsor: KU Leuven
• Collaborators: Universitaire Ziekenhuizen KU Leuven; University Hospital, Ghent; University Hospital, Antwerp; Kom Op Tegen Kanker

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: January 6, 2025
• First Submitted That Met QC Criteria: January 14, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 6, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: PET; Oncology; Pancreatic ductal adenocarcinoma; Positron emission tomography; Prospective; Nuclear imaging; [18F]-FAPI-74; Oesophagogastric adenocarcinoma; Clinically challenging situations; [18F]-FDG; [18F]AIF-FAPI-74
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Adenocarcinoma
• Other Study ID Numbers: S67792; 2024-512059-19 (EudraCT Number)

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