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

NCT06794372 | Recruiting Phase 2 DMC

• 2 other identifiers: FAPIHN2024-01881
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Head and Neck Squamous Cell Carcinoma HNSCC

Keywords

Head and Neck Squamous Cell Carcinoma; Cancer-associated fibroblasts; PET/CT; Lymph nodes; Tumor microenvironment; Fibroblast activation protein

Outcome Measures

Primary Outcomes (9)

• [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 Outcomes (1)

• Ability of [68Ga]Ga-FAPI-46 PET/CT to visualize tumor infiltration in lymph nodes

  2 months

Other Outcomes (4)

• Evaluation of FAP+ CAFs distribution

  1 year

• Comparison of [68Ga]Ga-FAPI-46 PET/CT with FAP immunoistochemistry

  1 year

• Evaluation of desmoplastic changes

  1 year

Study Arms (1)

HNSCC patients

EXPERIMENTAL

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

Interventions

[68Ga]Ga-FAPI-46 PET/CT DRUG

\[68Ga\]Ga-FAPI-46 PET/CT

HNSCC patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• John O. Prior: lead

Study Sites (1)

Centre hospitalier universitaire vaudois

Lausanne, Canton of Vaud, 1011, Switzerland

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Study Officials

• Niklaus Schaefer, MD

  Centre Hospitalier Universitaire Vaudois

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John O Prior, MD, PhD

CONTACT

+41 21 314 4348; john.prior@chuv.ch

Assistant

CONTACT

+41 21 314 4347

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: December 24, 2024
• First Posted: January 27, 2025
• Study Start: June 23, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)