[68Ga]Ga-FAPI-46 Positron Emission Tomography (PET) Scan to Improve the Imaging of Pancreatic and Bile Duct Cancer (PANSCAN-1)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer; Cholangiocarcinoma
• Intervention / Treatment: Diagnostic test: [68Ga]Ga-FAPI-46 PET/CT

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 63
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rutger B Henrar, MD; Phone Number: 003120 444 44 44; Email: r.b.henrar@amsterdamumc.nl
• Study Contact Backup: Name: Rutger-Jan Swijnenburg, MD, PhD; Email: r.j.swijnenburg@amsterdamumc.nl

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1081 HV
      • Recruiting
      • Amsterdam UMC, location VUmc
      • Contact: Rutger B Henrar, MD; Email: r.b.henrar@amsterdamumc.nl
      • Contact: R.J. Swijnenburg, MD, PhD; Email: r.j.swijnenburg@amsterdamumc.nl

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [68Ga]Ga-FAPI-46 PET/CT; 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; one or two [68Ga]Ga-FAPI-46 PET/CT scan(s)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc
• Collaborators: Leiden University Medical Center; Dutch Cancer Society
• Investigators: Principal Investigator: Rutger-Jan Swijnenburg, MD, PhD, Amsterdam UMC, location AMC

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: January 25, 2023
• First Submitted That Met QC Criteria: July 13, 2023
• First Posted (Estimated): July 24, 2023

Study Record Updates

• Last Update Posted (Estimated): July 24, 2023
• Last Update Submitted That Met QC Criteria: July 13, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: PET/CT; Positron Emission Tomography; FAPI; Radiopharmaceuticals; Fibroblast activation protein
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; FAPI-46
• Other Study ID Numbers: NL81511.018.22; 2022-001867-29 (EudraCT Number); 2022.0640 (Other Identifier: MERC approval number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The IPD will be shared anonymously only of the participants who have given informed consent to share their data for other research proposes.
• IPD Sharing Time Frame: At the time of journal article publication.
• IPD Sharing Access Criteria: Research data may be provided upon a reasonable request with necessary privacy provisions and only data form participants who have given informed consent for the use data for other research.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No