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Pancreatic NeoplasmsPhase 1NCT05172310

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

A Phase 1 study testing 68Ga-FAPI-46 and PET/CT in people with Pancreatic Neoplasms and Stomach Neoplasms, run by Karolinska University Hospital at 1 site in Sweden.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 19 years and older
What is being tested?
68Ga-FAPI-46 and PET/CT
Could I receive a placebo?
No, everyone receives an active treatment
How many people
410 participants
Where
1 siteSweden
Study dates
2 Jun 2021to 31 Mar 2029
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 11Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Rimma Axelsson, Professor contact

+46 708 227 622

rimma.axelsson@ki.se

Siri af Burén, MD contact

+46-739099570

siri.afburen@regionstockholm.se

Sweden1 site, 1 recruiting

  • Karolinska University Hospital Huddinge

    Stockholm, 14186

    Rimma Axelsson, Professor, +46 708 227 622, rimma.axelsson@ki.se

    Siri af Burén, MD, +46-739099570, siri.afburen@regionstockholm.se

    Recruiting

Other trials in Sweden

About this study

Official title: 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).

Read the 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.

Being tested
68Ga-FAPI-46, PET/CT
Keywords
68-Ga FAPI, PET/CT, Pancreatic Neoplasms, Stomach Neoplasms, Bile Duct Neoplasms, Fibroblast activating protein inhibitor, FAPI, Epithelial Ovarian Cancer
Medical subject headings
Pancreatic Neoplasms, Stomach Neoplasms, Bile Duct Neoplasms, Carcinoma, Ovarian Epithelial

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 68Ga-FAPI-46Drug

    • [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.

  • PET/CTDevice

    • 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.
Study groups in NCT05172310
Study groupRoleWhat they receive
Cancer patientsExperimental* Adults with suspected cancer of either pancreas, bile ducts or stomach * Adults with primary and recurrent epithelial ovarian cancer (EOC)
Receives: Drug: 68Ga-FAPI-46; Device: PET/CT
Non cancer patientsActive comparatorNon cancer patients operated for non-malignant diseases in pancreas during the same period of time will be investigated with the same procedure.
Receives: Drug: 68Ga-FAPI-46; Device: PET/CT

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: up to 18 months

Secondary outcomes (6)

  1. 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.

    Measured: up to 18 months

  2. 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

    Measured: up to 18 months

  3. 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.

    Measured: up to 5 years

  4. 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.

    Measured: up to 5 years

  5. 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.

    Measured: up to 18 months

  6. Safety of 68Ga-FAPI-46

    Frequency of

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

    Measured: up to 1 month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Dec 2021
  2. Study start2 Jun 2021
  3. Primary completion30 Jun 2024 (estimated)
  4. Study completion31 Mar 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Diagnosis
Allocation
Non-randomised
Intervention model
Parallel groups
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)
Enrolment
410 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05172310
Sponsor's protocol ID
H035-FAPI
Other IDs
2020-002568-30
Status last verified
Dec 2021
First submitted
16 Nov 2021
Last updated
29 Dec 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Davidson B, Goldberg I, Kopolovic J. Inflammatory response in cervical intraepithelial neoplasia and squamous cell carcinoma of the uterine cervix. Pathol Res Pract. 1997;193(7):491-5. doi: 10.1016/s0344-0338(97)80102-1.

    PubMed 9342755

  • Whatcott CJ, Posner RG, Von Hoff DD, Han H. Desmoplasia and chemoresistance in pancreatic cancer. In: Grippo PJ, Munshi HG, editors. Pancreatic Cancer and Tumor Microenvironment. Trivandrum (India): Transworld Research Network; 2012. Chapter 8. Available from http://www.ncbi.nlm.nih.gov/books/NBK98939/

    PubMed 22876390

  • Moon SB, Hur JM, Koo HH, Suh YL, Shin HB, Seo JM, Lee SK. Desmoplastic small round cell tumor of the stomach mimicking a gastric cancer in a child. J Korean Surg Soc. 2011 Jun;80 Suppl 1(Suppl 1):S80-4. doi: 10.4174/jkss.2011.80.Suppl1.S80. Epub 2011 Jun 17.

    PubMed 22066092

  • Baba AI, Câtoi C. TUMORS OF THE ALIMENTARY SYSTEM [Internet]. The Publishing House of the Romanian Academy; 2007 [cited 2020 Apr 1]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9565/

  • Fiori ME, Di Franco S, Villanova L, Bianca P, Stassi G, De Maria R. Cancer-associated fibroblasts as abettors of tumor progression at the crossroads of EMT and therapy resistance. Mol Cancer. 2019 Mar 30;18(1):70. doi: 10.1186/s12943-019-0994-2.

    PubMed 30927908

  • Ham IH, Lee D, Hur H. Role of Cancer-Associated Fibroblast in Gastric Cancer Progression and Resistance to Treatments. J Oncol. 2019 Jun 9;2019:6270784. doi: 10.1155/2019/6270784. eCollection 2019.

    PubMed 31281359

  • Ma Y, Zhu J, Chen S, Li T, Ma J, Guo S, Hu J, Yue T, Zhang J, Wang P, Wang X, Chen G, Liu Y. Activated gastric cancer-associated fibroblasts contribute to the malignant phenotype and 5-FU resistance via paracrine action in gastric cancer. Cancer Cell Int. 2018 Jul 20;18:104. doi: 10.1186/s12935-018-0599-7. eCollection 2018.

    PubMed 30038550

  • Ohlund D, Handly-Santana A, Biffi G, Elyada E, Almeida AS, Ponz-Sarvise M, Corbo V, Oni TE, Hearn SA, Lee EJ, Chio II, Hwang CI, Tiriac H, Baker LA, Engle DD, Feig C, Kultti A, Egeblad M, Fearon DT, Crawford JM, Clevers H, Park Y, Tuveson DA. Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer. J Exp Med. 2017 Mar 6;214(3):579-596. doi: 10.1084/jem.20162024. Epub 2017 Feb 23.

    PubMed 28232471

  • Brivio S, Cadamuro M, Strazzabosco M, Fabris L. Tumor reactive stroma in cholangiocarcinoma: The fuel behind cancer aggressiveness. World J Hepatol. 2017 Mar 28;9(9):455-468. doi: 10.4254/wjh.v9.i9.455.

    PubMed 28396716

  • Olive KP, Jacobetz MA, Davidson CJ, Gopinathan A, McIntyre D, Honess D, Madhu B, Goldgraben MA, Caldwell ME, Allard D, Frese KK, Denicola G, Feig C, Combs C, Winter SP, Ireland-Zecchini H, Reichelt S, Howat WJ, Chang A, Dhara M, Wang L, Ruckert F, Grutzmann R, Pilarsky C, Izeradjene K, Hingorani SR, Huang P, Davies SE, Plunkett W, Egorin M, Hruban RH, Whitebread N, McGovern K, Adams J, Iacobuzio-Donahue C, Griffiths J, Tuveson DA. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science. 2009 Jun 12;324(5933):1457-61. doi: 10.1126/science.1171362. Epub 2009 May 21.

    PubMed 19460966

  • Hingorani SR, Harris WP, Beck JT, Berdov BA, Wagner SA, Pshevlotsky EM, Tjulandin SA, Gladkov OA, Holcombe RF, Korn R, Raghunand N, Dychter S, Jiang P, Shepard HM, Devoe CE. Phase Ib Study of PEGylated Recombinant Human Hyaluronidase and Gemcitabine in Patients with Advanced Pancreatic Cancer. Clin Cancer Res. 2016 Jun 15;22(12):2848-54. doi: 10.1158/1078-0432.CCR-15-2010. Epub 2016 Jan 26.

    PubMed 26813359

  • Park JE, Lenter MC, Zimmermann RN, Garin-Chesa P, Old LJ, Rettig WJ. Fibroblast activation protein, a dual specificity serine protease expressed in reactive human tumor stromal fibroblasts. J Biol Chem. 1999 Dec 17;274(51):36505-12. doi: 10.1074/jbc.274.51.36505.

    PubMed 10593948

  • Scanlan MJ, Raj BK, Calvo B, Garin-Chesa P, Sanz-Moncasi MP, Healey JH, Old LJ, Rettig WJ. Molecular cloning of fibroblast activation protein alpha, a member of the serine protease family selectively expressed in stromal fibroblasts of epithelial cancers. Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5657-61. doi: 10.1073/pnas.91.12.5657.

    PubMed 7911242

  • Egger C, Cannet C, Gerard C, Suply T, Ksiazek I, Jarman E, Beckmann N. Effects of the fibroblast activation protein inhibitor, PT100, in a murine model of pulmonary fibrosis. Eur J Pharmacol. 2017 Aug 15;809:64-72. doi: 10.1016/j.ejphar.2017.05.022. Epub 2017 May 12.

    PubMed 28506908

  • Tillmanns J, Hoffmann D, Habbaba Y, Schmitto JD, Sedding D, Fraccarollo D, Galuppo P, Bauersachs J. Fibroblast activation protein alpha expression identifies activated fibroblasts after myocardial infarction. J Mol Cell Cardiol. 2015 Oct;87:194-203. doi: 10.1016/j.yjmcc.2015.08.016. Epub 2015 Aug 28.

    PubMed 26319660

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 68Ga-FAPI-46 and PET/CT in people with Pancreatic Neoplasms and Stomach Neoplasms, run by Karolinska University Hospital at 1 site in Sweden.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 29 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Rimma Axelsson, Professor (+46 708 227 622, rimma.axelsson@ki.se), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Diagnostic accuracy of FAPI-PET/CT in primary tumors (time frame: up to 18 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05172310, which also lists 41 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Dec 2021.

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