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

Phase 1

Recruiting

• Conditions: Bile Duct Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms; Epithelial Ovarian Cancer
• Interventions: Drug: 68Ga-FAPI-46; Device: PET/CT

• Registration Number: NCT05172310
• Lead Sponsor: Karolinska University Hospital

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.

Study Timeline

• Study Start: 2021-06-02
• Study First Submitted: 2021-11-16
• Status Verified: 2021-12
• Study First Submitted QC: 2021-12-13
• Last Update Submitted: 2021-12-13
• Study First Posted: 2021-12-29
• Last Update Posted: 2021-12-29
• Primary Completion: 2024-06-30
• Study Completion: 2029-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 410

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

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Non cancer patients	68Ga-FAPI-46	Non cancer patients operated for non-malignant diseases in pancreas during the same period of time will be investigated with the same procedure.
Cancer patients	68Ga-FAPI-46	* Adults with suspected cancer of either pancreas, bile ducts or stomach * Adults with primary and recurrent epithelial ovarian cancer (EOC)
Cancer patients	PET/CT	* Adults with suspected cancer of either pancreas, bile ducts or stomach * Adults with primary and recurrent epithelial ovarian cancer (EOC)
Non cancer patients	PET/CT	Non cancer patients operated for non-malignant diseases in pancreas during the same period of time will be investigated with the same procedure.

Primary Outcome Measures

Name	Time	Method
Diagnostic accuracy of FAPI-PET/CT in primary tumors	up to 18 months	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

Secondary Outcome Measures

Name	Time	Method
Diagnostic accuracy of FAPI-PET/CT in metastases	up to 18 months	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.
Safety of 68Ga-FAPI-46	up to 1 month	Frequency of; * Adverse Events (AEs); * Adverse Reactions (ARs)-; * Serious Adverse Events (SAEs) and; * Suspected Unexpected Serious Adverse Reactions (SUSARs).
FAPI-PET/CT and stroma markers as prognostic factors for Disease Free Survival (DFS)	up to 5 years	Disease Free Survival (DFS) at 1-year, 2-years and 5-years clinical follow-ups.
FAPI-PET/CT and stroma markers as prognostic factors for Overall Survival (OS)	up to 5 years	Overall Survival (OS) at 1-year, 2-years and 5-years clinical follow-ups.
Correlation between FAPI-PET/CT imaging results and those of conventional radiology	up to 18 months	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.
Immunohistochemistry	up to 18 months	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

Trial Locations

Locations (1)

Karolinska University Hospital Huddinge; 🇸🇪 Stockholm, Sweden