[18F]F-FAPI PET-CT to Identify Carcinoma of Unknown Primary Origin (FAPI for CUP)

The investigators will determine the proportion of CUP patients in whom the primary tumor can be identified by [18F]F-FAPI PET-CT.

Study Overview

• Status: Recruiting
• Conditions: Cancer of Unknown Primary
• Intervention / Treatment: Diagnostic test: [18F]F-FAPI PET-CT

Detailed Description

Carcinoma of unknown primary origin (CUP) is a diverse group of cancers defined by the presence of metastatic disease with no identified primary tumor after exhaustive diagnostic work-up. Absence of a known targetable primary tumor precludes patients from receiving tumor-specific evidence-based therapies which significantly impacts the life expectancy of CUP patients. In this investigator-initiated and patient association-driven, multi-center, prospective clinical study we aim to detect the primary tumor by PET-CT using the novel radiotracer [18F]F-fluoro fibroblast activation protein inhibitor (F-FAPI). We will include 50 patients (aged >18 year) who have been diagnosed with CUP after standard diagnostic work-up including FDG PET-CT. Participation in the study entails a one-time [18F]F-FAPI PET-CT examination in one of the six study centers (UMC Groningen, UMC Utrecht, Antoni van Leeuwenhoek, Radboudumc, Maastricht UMC, Erasmus MC). For the interpretation of images, central reading will be performed and results will be made available to the treating physician with an accompanying recommendation for additional diagnostics and/or treatment. After 6 months, the results of the [18F]F-FAPI PET-CT will be compared with patient follow up, including clinical, radiological and pathological outcome parameters. These findings will holistically be discussed in a multidisciplinary Truth Panel meeting to determine a uniform verdict with regard to the clinical value of [18F]F-FAPI for CUP. We hypothesize that [18F]F-FAPI PET-CT will detect the primary tumor in at least 15% of our CUP patients.¬

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sophie Veldhuijzen van Zanten, MD, PhD; Phone Number: 0107042006; Email: fapiforcup@erasmusmc.nl
• Study Contact Backup: Name: Esther Droogers; Phone Number: 0107042006; Email: e.droogers@erasmusmc.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Recruiting
    • Antoni van Leeuwenhoekziekenhuis
    • Contact: Serena Marchetti, MD, PhD; Phone Number: 0107042006; Email: fapiforcup@erasmusmc.nl
  • Groningen, Netherlands
    • Recruiting
    • UMC Groningen
    • Contact: Michel van Kruchten, MD, PhD; Phone Number: 0107042006; Email: fapiforcup@erasmusmc.nl
  • Maastricht, Netherlands
    • Recruiting
    • Maastricht UMC
    • Contact: Johanna Nin, MD, PhD; Phone Number: 0107042006; Email: fapiforcup@erasmusmc.nl
  • Nijmegen, Netherlands
    • Recruiting
    • Radboud UMC
    • Contact: Anja Timmer-Bonte, MD, PhD; Phone Number: 0107042006; Email: fapiforcup@erasmusmc.nl
  • Rotterdam, Netherlands
    • Recruiting
    • Erasmus Medical Center
    • Contact: Sophie Veldhuijzen van Zanten, MD, PhD; Phone Number: 0107042006; Email: fapiforcup@erasmusmc.nl
  • Utrecht, Netherlands
    • Recruiting
    • UMC Utrecht
    • Contact: Marnix Lam, MD, PhD; Phone Number: 0107042006; Email: fapiforcup@erasmusmc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years old
• Histologically-confirmed metastatic disease without identification of a primary tumor after standard diagnostic work-up, according to the national care pathway for CUP (in Dutch: Regionaal Zorgpad Primaire Tumor Onbekend), which includes at least an [18F]FDG PET-CT.

Exclusion Criteria:

• Patients with metastasis from a known primary tumor.
• Sarcomas, melanomas, germ cell tumors, neuroendocrine tumors and haematological malignancies whose exact site of origin is not established.
• History of malignancy within 5 years prior to [18F]F-FAPI PET-CT scan, with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%), such as adequately treated carcinoma in-situ of the cervix, nonmelanoma skin carcinoma, localized prostate cancer, ductal carcinoma in-situ, or Stage I uterine cancer.
• Prior systemic therapy for the treatment of CUP.
• Radiotherapy prior to [18F]F-FAPI PET-CT. Off note: radiotherapy with palliative intent for symptomatic skeleton lesions is allowed.
• Impaired renal function, defined as eGFR (MDRD) <25 ml/min/1,73 m2. An exception can be made in consultation with the treating physician.
• WHO performance status >2 (Vademecum).
• Pregnancy/breastfeeding. For the latter, temporary discontinuation may be considered.
• Known allergic reaction to therapeutic radiopharmaceuticals
• Inability to lie still on the back for the duration of PET-CT
• Any (other) condition, disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that may affect the interpretation of the results, or which might contribute substantially to the patient's experience of study burden (such as non-suppressible claustrophobia)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with CUP; Patients diagnosed with CUP after standard diagnostic work-up including an [18F]FDG PET-CT	Diagnostic test: [18F]F-FAPI PET-CT; Each patient will receive a FAPI PET-CT.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection of the primary tumor by [18F]F-FAPI PET-CT	The proportion of CUP patients in whom the primary tumor can be identified by [18F]F-FAPI PET-CT	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity, specificity, positive- and negative predictive value of [18F]F-FAPI PET-CT	These numbers will be calculated based on correlation between the outcome of the FAPI reading and the clinical outcome for the patient, i.e., correct or incorrect identification of a primary tumor (or not) by additional diagnostics or follow-up determined as such by a dedicated Truth Panel established for this study.	2 years

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Collaborators: Noordwest Ziekenhuisgroep; Academisch Ziekenhuis Maastricht; Dutch Cancer Society; Missie Tumor Onbekend; Cyclotron Noordwest BV
• Investigators: Principal Investigator: Sophie Veldhuijzen van Zanten, Erasmus Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: October 4, 2024
• First Submitted That Met QC Criteria: October 15, 2024
• First Posted (Actual): October 16, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 10, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Diagnostics; Cancer of Unknown Primary; PET-CT; [18F]F-FAPI
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplastic Processes; Neoplasm Metastasis; Carcinoma; Neoplasms, Unknown Primary
• Other Study ID Numbers: 2023-505592-69-00

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All individual participant data collected during the trial, after deidentification.
• IPD Sharing Time Frame: Beginning 3 months and ending 5 years after publication of the main results.
• IPD Sharing Access Criteria: Investigators who provide a sound proposal which has been approved by a review committee.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No