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

December 13, 2021 updated by: Rimma Axelsson, Karolinska University Hospital

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

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

410

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Sweden
      • Stockholm, Sweden, 14186
        • Recruiting
        • Karolinska University Hospital Huddinge
        • Principal Investigator:
          • Rimma Axelsson, Professor
        • Sub-Investigator:
          • Magnus Nilsson, Professor
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Johannes Matthias Löhr, Professor
        • Sub-Investigator:
          • Ulrika Joneborg, MD PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cancer patients
  • Adults with suspected cancer of either pancreas, bile ducts or stomach
  • Adults with primary and recurrent epithelial ovarian cancer (EOC)
Drug: 68Ga-FAPI-46
  • [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.
Device: PET/CT
  • 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.
Active Comparator: Non cancer patients
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
  • [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.
Device: PET/CT
  • 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diagnostic accuracy of FAPI-PET/CT in primary tumors
Time Frame: 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
up to 18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diagnostic accuracy of FAPI-PET/CT in metastases
Time Frame: 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.
up to 18 months
Immunohistochemistry
Time Frame: 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
up to 18 months
FAPI-PET/CT and stroma markers as prognostic factors for Disease Free Survival (DFS)
Time Frame: up to 5 years
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)
Time Frame: up to 5 years
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
Time Frame: 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.
up to 18 months
Safety of 68Ga-FAPI-46
Time Frame: up to 1 month

Frequency of

  • Adverse Events (AEs)
  • Adverse Reactions (ARs)-
  • Serious Adverse Events (SAEs) and
  • Suspected Unexpected Serious Adverse Reactions (SUSARs).
up to 1 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Karolinska University Hospital

Investigators

  • Principal Investigator: Rimma Axelsson, Professor, Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 2, 2021

Primary Completion (Anticipated)

June 30, 2024

Study Completion (Anticipated)

March 31, 2029

Study Registration Dates

First Submitted

November 16, 2021

First Submitted That Met QC Criteria

December 13, 2021

First Posted (Actual)

December 29, 2021

Study Record Updates

Last Update Posted (Actual)

December 29, 2021

Last Update Submitted That Met QC Criteria

December 13, 2021

Last Verified

December 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H035-FAPI
  • 2020-002568-30 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Stomach Neoplasms

Clinical Trials on 68Ga-FAPI-46

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Burkina Faso

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe