PET Imaging of Solid Tumors by a Novel Tracer, 68Ga-FAPI

Study Overview
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Brief Summary
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Cancers of the pancreas, bile ducts, stomach and ovaries are dismal diseases with most patients being diagnosed in advanced stages leading to a bad prognosis. These cancers can be difficult to diagnose and sometimes impossible to differentiate from underlying benign conditions. Establishing the correct diagnosis of primary cancer lesions and possible spread to other organs in time is pivotal for choosing the right therapy. Routinely applied staging procedures are however not always reliable. The main aim in this study is to evaluate the diagnostic accuracy of PET/CT with a novel radiotracer, FAPI, in the primary diagnosis of cancers in the pancreas, stomach and bile ducts as well as in patients with primary and recurrent epithelial ovarian cancer (EOC).

Detailed Description
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Malignant tumors exceeding 1-2 mm in size require formation of a supporting stroma, which includes vascular cells, inflammatory cells and fibroblasts . Several organs in the upper gastro-intestinal tract are known to develop tumors with strong desmoplastic reaction characterized by pervasive growth of tumor stroma. The pancreas, stomach, bile ducts and ovaries are all organs with this property. Within tumor stroma, a subpopulation of fibroblasts called cancer-associated fibroblasts (CAFs) are known to be involved in growth, migration and progression of the tumor. The Fibroblast Activation Protein (FAP) is one of the more prominent stroma markers and was the focus in the development of an agent for imaging and, eventually, even targeted radionuclide therapy. FAP is a type II membrane bound glycoprotein absent or only expressed at insignificant levels, in normal tissues in adults. The FAP inhibitor, FAPI, gets selectively enriched in tissues where its target protein is expressed and there is no or very limited FAPI uptake in all normal organs. This opens new possibilities for the detection of malignant lesions with higher stromal content based on the high contrast positron emission tomography (PET) images obtained with a 68-Gallium (68Ga) radiolabeled - FAPI compound. As cancers in pancreas, stomach, bile ducts and ovaries are all characterized by abundant desmoplasia that constitutes up to 90% of the total tumor volume and contains extracellular matrix, immune cells, vasculature and CAFs, it would be suitable for targeted imaging with FAPI. Preliminary studies show elevated FAPI uptake in many tumors rich in fibroblasts along with low background uptake. The main objective of this prospective study is to improve non-invasive diagnostics of malignancy in tumors of pancreas, stomach, bile ducts and ovaries, all known for a strong desmoplastic reaction by evaluating the diagnostic accuracy of PET/CT with a novel radiotracer, FAPI in the primary diagnosis and staging of such cancers.

Official Title
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PET Imaging of Tumors in Pancreas, Bile Ducts, Stomach and Ovaries by a Novel Tracer, 68Ga-FAPI-46 = Fibroblast Activation Protein Inhibitor

Conditions
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Pancreatic Neoplasms, Stomach Neoplasms, Bile Duct Neoplasms, Epithelial Ovarian Cancer

Intervention / Treatment
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* Drug: 68Ga-FAPI-46
* Device: PET/CT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Consecutive patients scheduled for surgical removal of either a pancreatic, biliary or gastric lesion. - Consecutive patients scheduled for primary surgical removal of early stage epithelial ovarian cancer (EOC), interval debulking surgery of EOC or surgical removal or tissue biopsy of recurrent EOC Signed informed consent. Common Exclusion Criteria for all study populations: Age ≤18 year Pregnancy and lactation Significantly reduced renal function Allergy to iodinated contrast media Subjects that for some reason are unable to exercise their own rights, such as cognitive function impairment. Additional Exclusion Criteria for study populations with either pancreatic-, gastric or bile duct cancer: • Known metastatic disease

Ages Eligible for Study
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Minimum Age: 19 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Investigators select subjects that are scheduled for surgical removal of either a malignant lesion in the pancreas, bile ducts, or stomach (first arm) surgical removal of primary stage epithelial cancer of the ovary (EOC), interval debulking surgery (IDS) of EOC or surgical removal/tissue biopsy of recurrent EOC (first arm) surgical removal of a benign lesion in the pancreas (second arm) All patients will undergo a PET/CT with the interventional drug/radiotracer 68Ga-FAPI-46 before surgery.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cancer patients<br>Adults with suspected cancer of either pancreas, bile ducts or stomach Adults with primary and recurrent epithelial ovarian cancer (EOC) | Drug: 68Ga-FAPI-46<br>* [68Ga] Ga-FAPI-46 Solution for Injection is manufactured at the Karolinska University Hospital Radiopharmacy facilities, for imaging studies with Positron Emission Tomography (PET). It is a radiolabelled Fibroblast Activation Protein Inhibitor (FAPI) used for PET of a number of different cancer entities. Depending on the labelling yield 50 - 370 megabecquerel (MBq) of [68Ga] Ga-FAPI-46 Solution for Injection will be administered intravenously 60 minutes prior to whole-body PET image acquisition.<br>Device: PET/CT<br>* Combined PET and computed tomography (CT) imaging with 68Ga-FAPI-46 will be performed using the same protocol on a Biograph 6 PET/CT scanner (Siemens, Erlangen, Germany) and General Electrics (GE) Discovery 710, Milwaukee, Wisconsin, USA at the Department of Nuclear Medicine, Karolinska Huddinge within 2 weeks before surgery. PET/CT imaging will be performed in dynamic mode at one bed position centered over the primary tumor for 45 minutes. At 60 minutes post injection, a whole-body PET will be acquired.<br>|
| Active Comparator: Non cancer patients<br>Non cancer patients operated for non-malignant diseases in pancreas during the same period of time will be investigated with the same procedure. | Drug: 68Ga-FAPI-46<br>* [68Ga] Ga-FAPI-46 Solution for Injection is manufactured at the Karolinska University Hospital Radiopharmacy facilities, for imaging studies with Positron Emission Tomography (PET). It is a radiolabelled Fibroblast Activation Protein Inhibitor (FAPI) used for PET of a number of different cancer entities. Depending on the labelling yield 50 - 370 megabecquerel (MBq) of [68Ga] Ga-FAPI-46 Solution for Injection will be administered intravenously 60 minutes prior to whole-body PET image acquisition.<br>Device: PET/CT<br>* Combined PET and computed tomography (CT) imaging with 68Ga-FAPI-46 will be performed using the same protocol on a Biograph 6 PET/CT scanner (Siemens, Erlangen, Germany) and General Electrics (GE) Discovery 710, Milwaukee, Wisconsin, USA at the Department of Nuclear Medicine, Karolinska Huddinge within 2 weeks before surgery. PET/CT imaging will be performed in dynamic mode at one bed position centered over the primary tumor for 45 minutes. At 60 minutes post injection, a whole-body PET will be acquired.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic accuracy of FAPI-PET/CT in primary tumors | To validate the proportion of false-positive and false-negative FAPI-PET/CT findings in primary pancreas, biliary and gastric tumors as well as in primary and recurrent EOC with postsurgical or true cut biopsy histopathological confirmation of diagnosis (PAD) as a reference standard | up to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic accuracy of FAPI-PET/CT in metastases | To validate the proportion of false-positive and false-negative FAPI-PET/CT findings in resected metastatic tumor tissue/resected lymph nodes, in primary (and recurrent for EOC) tumors, by using postsurgical tissue samples or biopsies as well as PAD as a reference standard. | up to 18 months | 
| Immunohistochemistry | To investigate the correlation between in-vivo uptake of FAPI and ex-vivo immunohistochemically determined biomarker expression in the stroma of these tumors (both benign and malignant) with PAD as a reference standard | up to 18 months | 
| FAPI-PET/CT and stroma markers as prognostic factors for Disease Free Survival (DFS) | Disease Free Survival (DFS) at 1-year, 2-years and 5-years clinical follow-ups. | up to 5 years | 
| FAPI-PET/CT and stroma markers as prognostic factors for Overall Survival (OS) | Overall Survival (OS) at 1-year, 2-years and 5-years clinical follow-ups. | up to 5 years | 
| Correlation between FAPI-PET/CT imaging results and those of conventional radiology | To investigate the difference in diagnostic accuracy of FAPI-PET/CT compared to conventional imaging diagnostics performed according to clinical routine, by using postsurgical PAD as a reference standard both for differentiation between malignant and benign lesions as well as for N and M staging. | up to 18 months | 
| Safety of 68Ga-FAPI-46 | Frequency of Adverse Events (AEs) Adverse Reactions (ARs)- Serious Adverse Events (SAEs) and Suspected Unexpected Serious Adverse Reactions (SUSARs). | up to 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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68-Ga FAPI, PET/CT, Pancreatic Neoplasms, Stomach Neoplasms, Bile Duct Neoplasms, Fibroblast activating protein inhibitor, FAPI, Epithelial Ovarian Cancer