[68Ga]Ga-FAPI-46 Positron Emission Tomography (PET) Scan to Improve the Imaging of Pancreatic and Bile Duct Cancer

Study Overview
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Brief Summary
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The goal of this clinical trial is to evaluate the clinical use of [68Ga]Ga-FAPI-46 PET (positron emission tomography)/CT (computed tomography) imaging in patients with pancreatic or bile duct cancer. The study consists of three parts and patients can only participate in one part of the study. The main questions the study aims to answer are: In part A: What is the best timing and scanprotocol of a [68Ga]Ga-FAPI-46 PET/CT scan? In part B: Are the results of the simplified scan protocol repeatable? In part C: What is the accuracy of [68Ga]Ga-FAPI-46 PET/CT to detect pancreatic cancer and is it able to detect the effect of chemotherapy on pancreatic cancer lesions? Participants in this study will be asked to undergo the following: In part A: participants will undergo 1 [68Ga]Ga-FAPI-46 PET/CT scan and will have 2 venous canullas and 1 arterial cannula placed. In part B: participants will undergo 2 [68Ga]Ga-FAPI-46 PET/CT scans and will have a venous cannula placed for each scan. In part C: participants will undergo 2 [68Ga]Ga-FAPI-46 PET/CT scans and will have a venous cannula placed for each scan.

Detailed Description
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Pancreaticobiliary cancer patients have a dismal prognosis. Therefore, patient stratification for the proper primary treatment is crucial to prevent unnecessary surgery and opens up the opportunity for novel (multimodal) treatment. Unfortunately, conventional imaging modalities are not sensitive enough to detect small tumor lesions or differentiate between benign and malignant tissue after neoadjuvant therapy. Tumor-specific imaging, using PET/CT imaging, can identify tumor tissue more accurately and therefore can improve lesion detection and patient stratification. Fibroblast activation protein (FAP) shows promise as a target to identify pancreaticobiliary cancers, lymph node metastases, and residual disease after neoadjuvant therapy. The FAP targeted inhibitor (FAPI) is developed to target FAP and has been labelled to the Gallium-68 (68Ga) radioisotope, resulting in the [68Ga]Ga-FAPI-46 tracer. This study will be a three part monocenter study focusing on the clinical evaluation of [68Ga]Ga-FAPI-46. In part A, the pharmacokinetics of this tracer will be studied and the simplified method(s) to quantify tracer uptake will be validated. In part B, a test-retest study will be performed to assess the repeatability of these simplified quantitative methods. In part C, the sensitivity and feasibility of therapy response monitoring will be investigated.

Official Title
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[68Ga]Ga-FAPI-46 Positron Emission Tomography in Pancreaticobiliary Cancers: a Pharmacokinetics, Repeatability and Diagnostic Accuracy Study

Conditions
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Pancreatic Cancer, Cholangiocarcinoma

Intervention / Treatment
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* Diagnostic Test: [68Ga]Ga-FAPI-46 PET/CT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 18 years or older. Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations. Additional Part A: patients with pancreaticobiliary cancer (pancreatic, intra- or extrahepatic cholangiocarcinoma) and a tumor size of >20mm on CT. Additional Part B: patients with primary pancreatic (or pancreaticobiliary) cancer (depending on the results of part A) and a tumor size of >20mm on CT. No treatment may be given in between the two scans. Additional Part C: patients with pathologically proven pancreatic ductal adenocarcinoma, eligible for neoadjuvant therapy before surgical resection. Exclusion Criteria: Women who are pregnant and/or lactating. Medical or psychiatric conditions that compromise the patient's ability to give informed consent. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. Impaired renal function (creatinine clearance <60 mL/min according to the Cockcroft-Gault equation. Leucocytes (WBC) ≤3.0 x 10^9/l Platelets ≤ 100 x 10^9 /l Hemoglobin ≤ 6 mmol/l Known hypersensitivity to drugs comparative to [68Ga]Ga-FAPI-46, or any of the excipients of [68Ga]Ga-FAPI-46. Inability to undergo PET/CT scanning (e.g. claustrophobia, weight limits or inability to tolerate lying for the duration of a PET/CT scan ( 90 min)). Additional Part A: • Contra-indication for arterial cannula (e.g. inadequate circulation of extremity, positive Allen test, severe atherosclerosis, coagulant disorder (INR >1.4 or APTT >50)). Additional Part C: Not eligible for surgery after neoadjuvant chemotherapy. If based on the first FAPI-46 PET/CT, there is a suspicion of metastatic disease the images will be discussed in the multidisciplinary meeting and one additional imaging modality (and a biopsy, if this would lead to a change of treatment strategy) can be used to confirm the suspicion. If metastatic disease is confirmed the patient will be excluded.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: Monocenter, non-randomized, non-blinded, prospective observational study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: [68Ga]Ga-FAPI-46 PET/CT<br>Depending on study fase: injection(s) with [68Ga]Ga-FAPI-46 for one or two [68Ga]Ga-FAPI-46 PET/CT scan(s) | Diagnostic Test: [68Ga]Ga-FAPI-46 PET/CT<br>* one or two [68Ga]Ga-FAPI-46 PET/CT scan(s)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Semi quantitative measurements of [68Ga]Ga-FAPI-46 tracer | [68Ga]Ga-FAPI-46 tracer uptake (SUV max, SUVmean and SUVpeak) in primary tumour, lymph node and distant metastases and background uptake in a dynamic scan protocol (expressed in Standardised Uptake Values). | 3 months | 
| Blood activity measurements of [68Ga]Ga-FAPI-46 tracer | [68Ga]Ga-FAPI-46 blood activity concentration (expressed in kBq/ml) | 3 months | 
| Plasma to blood ratio of [68Ga]Ga-FAPI-46 tracer | [68Ga]Ga-FAPI-46 plasma to blood ratio (expressed in kBq/ml) | 3 months | 
| Repeatability | The daily variability (average percentage of difference) of the preferred simplified method for quantification of [68Ga]Ga-FAPI-46. | 3 months | 
| Diagnostic accuracy | Per lesion analysis of diagnostic accuracy of [68Ga]Ga-FAPI-46 PET/CT using visual, semi quantitative and histopathological results. | 3 months | 
| Response monitoring | Accuracy of response monitoring of neoadjuvant therapy using [68Ga]Ga-FAPI-46 PET/CT in comparison to conventional imaging and histopathological results. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Agreement imaging and pathology | Percentage of agreement between tumor uptake on the [68Ga]Ga-FAPI-46 PET/CT scan, histopathologic evidence of tumor, and the expression of FAP (IHC). | 3 months | 
| Agreement imaging modalities | Percentage of agreement between different imaging modalities ([68Ga]Ga-FAPI-46 PET/CT and CT , MRI or FDG PET/CT). | 3 months | 
| Imaging and tumor regression | Correlation between [68Ga]Ga-FAPI-46 PET/CT signal to tumor regression (MDACC method). | 3 months | 
| Change of therapy management | Percentage of potential change of therapy management enabled by [68Ga]Ga-FAPI-46 PET/CT. | 3 months | 
| Response prediction first scan | Sensitivity of response prediction of neoadjuvant therapy based on the first [68Ga]Ga-FAPI-46 PET/CT. | 3 months | 
| Resectability (based on DPCG criteria) | Accuracy of determining surgical resectability, based on DPCG criteria, using [68Ga]Ga-FAPI-46 PET/CT. | 3 months | 
| Diagnostic accuracy of incidental findings | Determine the diagnostic accuracy of incidental findings on [68Ga]Ga-FAPI-46 PET/CT using other imaging modalities, histopathological results, biopsy results, follow-up or a combination of the previous. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Positron Emission Tomography, PET/CT, FAPI, Fibroblast activation protein, Radiopharmaceuticals