Clinical trial NCT06794372: [68Ga]Ga-FAPI-46 in Staging of Head and Neck Carcinomas
Official title: [68Ga]Ga-FAPI-46 PET/CT in Early Detection of Lymph Node Metastasis in Head and Neck Squamous Cell Carcinomas
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
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
Lead sponsor: University of Lausanne Hospitals
Sponsor class: OTHER
First posted: 2025-01-27
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: [68Ga]Ga-FAPI-46 PET/CT imaging results: tumor size
timeFrame: 6 weeks
measure: [68Ga]Ga-FAPI-46 PET/CT imaging results: tumor volume
timeFrame: 6 weeks
measure: [68Ga]Ga-FAPI-46 PET/CT imaging results: tumor SUVmax
timeFrame: 6 weeks
measure: [68Ga]Ga-FAPI-46 PET/CT imaging results: number of lesions
timeFrame: 6 weeks
measure: [68Ga]Ga-FAPI-46 PET/CT imaging results: lesion site
timeFrame: 6 weeks
measure: [68Ga]Ga-FAPI-46 PET/CT imaging results: lesion size
timeFrame: 6 weeks
measure: [68Ga]Ga-FAPI-46 PET/CT imaging results: lesion volume
timeFrame: 6 weeks
measure: [68Ga]Ga-FAPI-46 PET/CT imaging results: lesion SUVmax
timeFrame: 6 weeks
measure: [68Ga]Ga-FAPI-46 PET/CT imaging results: TNM tumor stage
timeFrame: 6 weeks
Secondary outcomes:
measure: Ability of [68Ga]Ga-FAPI-46 PET/CT to visualize tumor infiltration in lymph nodes
timeFrame: 2 months
Other outcomes:
measure: Evaluation of FAP+ CAFs distribution
timeFrame: 1 year
measure: Comparison of [68Ga]Ga-FAPI-46 PET/CT with FAP immunoistochemistry
timeFrame: 1 year
measure: Evaluation of desmoplastic changes
timeFrame: 1 year
measure: Evaluation of modifications to the current therapeutic approach (questionnaire)
timeFrame: Questionnaire 2 ± 1 week after surgery
Locations:
city: Lausanne
country: Switzerland
facility: Centre hospitalier universitaire vaudois
state: Vaud
Study officials:
affiliation: Centre Hospitalier Universitaire Vaudois
name: Niklaus Schaefer, MD
role: PRINCIPAL_INVESTIGATOR
References: