Development of Patient Derived Xenografts (PDXs) and Analysis of Tyrosine Kinase Receptor Expression in Patients With Squamous Cell Head and Neck Cancer (HNSCC) to Study Resistance Mechanisms Induced by Standard Therapy

Protocol TitleDevelopment of Patient-Derived Xenografts (PDXs) and analysis of tyrosine kinase receptor expression in patients with Head and Neck Squamous Cell Carcinoma (HNSCC) to study resistance mechanisms induced by standard therapy (SPAR).Brief SummaryThe SPAR study aims to better understand why some patients with head and neck squamous cell carcinoma (HNSCC) stop responding to standard treatments. Researchers will create a specialized set of "Patient-Derived Xenografts" (PDXs)-biological models developed by grafting fresh human tumor samples into immunocompromised mice.By analyzing these models alongside historical patient samples, the study will investigate the expression of various protein receptors (such as the ERBB family, MET, and AXL) and their signaling pathways. The goal is to identify alternative therapeutic targets that could allow the use of existing drugs approved for other cancers, providing new hope for patients with drug-resistant HNSCC.Study DesignStudy Type: Combined Prospective and Retrospective observational/translational study.Prospective Phase: Over 5 years, researchers will collect fresh tumor and blood samples from patients undergoing surgery. These samples will be used to develop the PDX models and undergo genetic and molecular characterization (NGS, IHC, WB).Retrospective Phase: Researchers will analyze archived biological materials (FFPE samples) from patients treated over the last 10 years to evaluate molecular markers and resistance pathways.Duration: 6.5 years total (5 years for enrollment, 1.5 years for data analysis).Participant PopulationTotal Enrollment: 120 patients.Retrospective Group (approx. 40 cases): Patients with HNSCC treated with Cetuximab in the last 10 years.Prospective Group (80 cases): Patients with HNSCC scheduled for surgery at the IRCCS Policlino S. Orsola in Bologna.Eligibility CriteriaInclusion Criteria:Age $\\ge$ 18 years at the time of tissue collection.Signed informed consent.Confirmed histological diagnosis of squamous cell carcinoma of the head and neck.For the retrospective group: Prior treatment with Cetuximab.For the prospective group: Candidates for surgery within the Otorhinolaryngology or Maxillofacial units.Exclusion Criteria:Retrospective: Biological material of insufficient quality or quantity for immunohistochemical/molecular analysis.Prospective: Any diagnosis other than squamous cell carcinoma.Outcome Measures / MethodologyThe study will utilize advanced molecular techniques to map the tumor landscape, including:Genomic/Transcriptomic Analysis: Next-Generation Sequencing (NGS), qPCR, and ddPCR to identify mutations and gene rearrangements.Protein Expression: ELISA, Immunohistochemistry (IHC), Immunoblotting, and QF-Pro/PLA technology to evaluate receptor activity.Virology: Identification of HPV presence and genotypes.

NCT Number	NCT07471009
Lead Sponsor	IRCCS Azienda Ospedaliero-Universitaria di Bologna
Conditions	Squamous Cell Tumors of the Head and Neck (HNSCC)
Enrollment	120 participants
Start Date	2026-03-31
Primary Completion	2026-03-31 (estimated)
Study Completion	2032-10-01 (estimated)
Updated on ClinicalTrials.gov	2026-03-13