Clinical trial NCT05172310: PET Imaging of Solid Tumors by a Novel Tracer, 68Ga-FAPI
Official title: PET Imaging of Tumors in Pancreas, Bile Ducts, Stomach and Ovaries by a Novel Tracer, 68Ga-FAPI-46 = Fibroblast Activation Protein Inhibitor
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Pancreatic Neoplasms
Stomach Neoplasms
Bile Duct Neoplasms
Epithelial Ovarian Cancer
Keywords: 68-Ga FAPI
PET/CT
Pancreatic Neoplasms
Stomach Neoplasms
Bile Duct Neoplasms
Fibroblast activating protein inhibitor
FAPI
Epithelial Ovarian Cancer
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
First posted: 2021-12-29
Enrollment: 410
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: DIAGNOSTIC

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Diagnostic accuracy of FAPI-PET/CT in primary tumors
timeFrame: up to 18 months
Secondary outcomes:
measure: Diagnostic accuracy of FAPI-PET/CT in metastases
timeFrame: up to 18 months
measure: Immunohistochemistry
timeFrame: up to 18 months
measure: FAPI-PET/CT and stroma markers as prognostic factors for Disease Free Survival (DFS)
timeFrame: up to 5 years
measure: FAPI-PET/CT and stroma markers as prognostic factors for Overall Survival (OS)
timeFrame: up to 5 years
measure: Correlation between FAPI-PET/CT imaging results and those of conventional radiology
timeFrame: up to 18 months
measure: Safety of 68Ga-FAPI-46
timeFrame: up to 1 month
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Karolinska University Hospital Huddinge
Study officials:
affiliation: Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital
name: Rimma Axelsson, Professor
role: PRINCIPAL_INVESTIGATOR
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