[68Ga]Ga-FAPI-46 in Staging of Head and Neck Carcinomas (FAPIHN)

[68Ga]Ga-FAPI-46 PET/CT in Early Detection of Lymph Node Metastasis in Head and Neck Squamous Cell Carcinomas

The trial focuses on assessing the role of [68Ga]Ga-FAPI-46 in head and neck squamous cell carcinomas (HNSCC) staging before surgery. In the context of metastasis, cancer-associated fibroblasts (CAFs) emerge as pivotal contributors to the creation of a microenvironment conducive to future metastases. CAFs exert their influence through intricate mechanisms, including the remodeling of the extracellular matrix by secreting proteins such as collagen and fibronectin. This process enhances the structural support for cancer cell invasion into adjacent tissues. Additionally, CAFs play a central role in promoting angiogenesis, ensuring an adequate blood supply to the tumor, which may also facilitate the entry of cancer cells into the bloodstream. Through modulation of immune responses within the tumor microenvironment, CAFs establish an immunosuppressive milieu, providing a permissive environment for cancer cell survival and dissemination. Collectively, the orchestrated activities of CAFs contribute to the preparation of a metastatic niche, influencing the microenvironment at both primary and secondary sites and enhancing the likelihood of successful metastasis.

Employing [68Ga]Ga-FAPI-46 PET/CT imaging to target activated CAFs may hold the potential to discern lymph nodes (LNs) predisposed to future metastases in HNSCC. The use of this imaging modality offers a unique opportunity to visualize and assess the presence and activity of CAFs within the tumor microenvironment. By targeting the fibroblast activation protein (FAP), a receptor enriched on CAFs, this imaging approach provides a specific and sensitive mean to identify regions where the microenvironment may favor metastatic progression.

In this research endeavor, the primary objective is to highlight the additional value of [68Ga]Ga-FAPI-46 PET/CT into the standard pre-surgical imaging protocol. Additionally, the study will evaluate the efficacy of FAP positon emission tomography (PET) in primary tumor delineation. Imaging based on [68Ga]Ga-FAPI-46 allows the identification of CAFs, specifically by exploiting their increased FAP expression. The study aims also to systematically compare the [68Ga]Ga-FAPI-46 PET/CT signals with the characteristics of resected lymph nodes, seeking to ascertain the capability of FAPI PET imaging in identifying premetastatic conditions. By comparing the [68Ga]Ga-FAPI-46 PET signal and the histopathological features of resected lymph nodes, the goal is to validate the potential of [68Ga]Ga-FAPI-46 PET imaging as a tool for early detection of premalignant or metastatic conditions in the lymphatic system before surgical intervention. The ability to pinpoint lymph nodes at risk for future metastases could revolutionize clinical decision-making, by facilitating a more nuanced understanding of disease spread, thereby informing personalized treatment strategies and potentially improving patient outcomes.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Squamous Cell Carcinoma HNSCC
• Intervention / Treatment: Drug: [68Ga]Ga-FAPI-46 PET/CT

Detailed Description

[68Ga]Ga-FAPI-46 PET/CT is an advanced imaging technique utilized in nuclear medicine for the evaluation of various cancers. The imaging agent [68Ga]Ga-FAPI-46 specifically targets FAP, a protein overexpressed by CAFs in the tumor microenvironment. This targeted approach allows for precise visualization of FAP-positive tumors, aiding in the detection, staging, and assessment of therapeutic response. The integration of PET and CT modalities provides both functional and anatomical information, enhancing the accuracy of the imaging results. In this study, the investigators will specifically evaluate the application of [68Ga]Ga-FAPI-46 PET/CT in patients diagnosed with HNSCC who are scheduled for primary clinical resection. This research aims to explore the potential of [68Ga]Ga-FAPI-46 PET/CT in guiding treatment decisions and optimizing the management of HNSCC, contributing valuable insights to the growing knowledge in precision oncology.

Patients with confirmed HNSCC and planned to undergo tumor and LN dissection surgery will be recruited for this project. The included patients will follow their standard-of-care clinical investigations according to current guideline-based recommendations.

Patients will receive [68Ga]Ga-FAPI-46 in a dose of 2MBq/kg (+/-15%) as an IV injection. The total administered dose will be between 80 and 200MBq. 60 minutes (+/- 10min) after the injection, low-dose, non-contrast-enhanced PET/CT will be acquired for about 20 minutes.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: John O Prior, MD, PhD; Phone Number: +41 21 314 4348; Email: john.prior@chuv.ch
• Study Contact Backup: Name: Assistant; Phone Number: +41 21 314 4347

Study Locations

• Switzerland
  • Canton of Vaud
    • Lausanne, Canton of Vaud, Switzerland, 1011
      • Recruiting
      • Centre Hospitalier Universitaire Vaudois
      • Contact: John O Prior, MD, PhD; Phone Number: +41 21 314 4348; Email: john.prior@chuv.ch
      • Principal Investigator: Niklaus Schaefer, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥18 years old
• Karnofsky index ≥80%
• Patients with operable head and neck cancer presenting histologically proven HNSCC (including Oral Cavity Cancer, Pharyngeal Cancer, Laryngeal Cancer)
• Patients with at least one nodal metastasis
• Patients scheduled for neck dissection
• SOC imaging (MRI, ceCT and 18F-FDG-PET/CT) performed as pre-surgery exams
• Written informed consent obtained

Exclusion Criteria:

• Known pregnancy or ongoing breast feeding
• Claustrophobia
• Severe renal insufficiency (GFR<30 mL/min/1,73 m2)
• Liver enzymes (ALAT, ASAT)>5 times the standard upper limit
• Bilirubin>3 times the standard upper limit
• Hemoglobin<8 g/dL
• Absolute neutrophil count<1000/mm3
• Platelets<75000/µL
• insufficient knowledge of project language, inability to give consent or to follow trial-associated procedures
• the patient makes use of his/her "right not to know" and refuses to be informed about incidental findings

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: HNSCC patients; Patients with operable head and neck cancer presenting histologically proven HNSCC, planned to undergo surgery (tumour and lymph node dissection), and who will benefit, as standard of care, from cervical MRI, ceCT and 18F-FDG PET/CT.	Drug: [68Ga]Ga-FAPI-46 PET/CT; [68Ga]Ga-FAPI-46 PET/CT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[68Ga]Ga-FAPI-46 PET/CT imaging results: tumor size	The tumor size (mm*mm) measured by 68Ga-FAPI-46 PET/CT will be reported. Results will be compared to the clinically indicated standard imaging (FDG PET/CT, ceCT and MRI).	6 weeks
[68Ga]Ga-FAPI-46 PET/CT imaging results: tumor volume	The tumor volume (mm^3) measured by 68Ga-FAPI-46 PET/CT will be reported. Results will be compared to the clinically indicated standard imaging (FDG PET/CT).	6 weeks
[68Ga]Ga-FAPI-46 PET/CT imaging results: tumor SUVmax	The SUVmax of the tumor measured by 68Ga-FAPI-46 PET/CT will be reported. Results will be compared to the clinically indicated standard imaging (FDG PET/CT).	6 weeks
[68Ga]Ga-FAPI-46 PET/CT imaging results: number of lesions	The number of lesions (for nearby lymph nodes and distant metastases) visible by 68Ga-FAPI-46 PET/CT will be reported. Results will be compared to the clinically indicated standard imaging (FDG PET/CT, ceCT and MRI).	6 weeks
[68Ga]Ga-FAPI-46 PET/CT imaging results: lesion site	The site of lesions (for nearby lymph nodes and distant metastases) visible by 68Ga-FAPI-46 PET/CT will be reported. Results will be compared to the clinically indicated standard imaging (FDG PET/CT, ceCT and MRI).	6 weeks
[68Ga]Ga-FAPI-46 PET/CT imaging results: lesion size	The size (mm*mm) of lesions (for nearby lymph nodes and distant metastases) visible by 68Ga-FAPI-46 PET/CT will be reported. Results will be compared to the clinically indicated standard imaging (FDG PET/CT, ceCT and MRI).	6 weeks
[68Ga]Ga-FAPI-46 PET/CT imaging results: lesion volume	The volume (mm^3) of lesions (for nearby lymph nodes and distant metastases) visible by 68Ga-FAPI-46 PET/CT will be reported. Results will be compared to the clinically indicated standard imaging (FDG PET/CT).	6 weeks
[68Ga]Ga-FAPI-46 PET/CT imaging results: lesion SUVmax	The SUVmax of lesions (for nearby lymph nodes and distant metastases) visible by 68Ga-FAPI-46 PET/CT will be reported. Results will be compared to the clinically indicated standard imaging (FDG PET/CT).	6 weeks
[68Ga]Ga-FAPI-46 PET/CT imaging results: TNM tumor stage	The TNM stage calculated by 68Ga-FAPI-46 PET/CT will be reported. Results will be compared to the clinically indicated standard imaging (FDG PET/CT, ceCT and MRI).	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ability of [68Ga]Ga-FAPI-46 PET/CT to visualize tumor infiltration in lymph nodes	Histopathology of clinically indicated resected lymph node specimen will be performed. [68Ga]Ga-FAPI-46 PET/CT results and tumor infiltration findings by histology will be compared (lesions defined positive/negative as a result of the two techniques).	2 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of FAP+ CAFs distribution	Presence (positive/negative) of FAP+ cells in tumor center, tumor invasive margin and adjacent normal tissue.	1 year
Comparison of [68Ga]Ga-FAPI-46 PET/CT with FAP immunoistochemistry	The ability of [68Ga]Ga-FAPI-46 PET/CT to identify FAP+ cells in lymph node lesions will be evaluated. The measurement will compare if lesions are defined as positive/negative by FAPI PET (positive/negative) and by histology showing FAP+ CAFs in the lesion.	1 year
Evaluation of desmoplastic changes	Resected LNs will be analyzed by histopathology to determine the presence of desmoplastic changes. Desmoplastic changes will be expressed as the expression of specific molecular markers.	1 year
Evaluation of modifications to the current therapeutic approach (questionnaire)	Modifications to the current therapeutic approach will be evaluated by the head and neck surgeon, who will fill out a questionnaire about the foreseen therapeutic approach with and without taking into account the results of the [68Ga]Ga-FAPI-46 PET/CT. The questionnaire will contain yes/no questions or multiple choice questions.	Questionnaire 2 ± 1 week after surgery

Collaborators and Investigators

• Sponsor: John O. Prior
• Investigators: Principal Investigator: Niklaus Schaefer, MD, Centre Hospitalier Universitaire Vaudois

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: December 24, 2024
• First Submitted That Met QC Criteria: January 20, 2025
• First Posted (Actual): January 27, 2025

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: PET/CT; Head and Neck Squamous Cell Carcinoma; Tumor microenvironment; Lymph nodes; Cancer-associated fibroblasts; Fibroblast activation protein
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; FAPI-46
• Other Study ID Numbers: FAPIHN; 2024-01881 (Registry Identifier: BASEC)

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
• product manufactured in and exported from the U.S.: No