Real-time Detection of ctDNA and/or HPV DNA in High-risk Locally-advanced Head and Neck Squamous Cell Carcinoma

Study Overview
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Brief Summary
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This research study will include patients with high risk locally advanced head and neck squamous cell carcinoma (LA-HNSCC) of the oral cavity, oropharynx, hypopharynx or larynx and patients that are starting on standard definitive treatment. Patients with both stage III HPV positive and stage III HPV negative will be included. In this study, we aim to evaluate feasibility of ctDNA and/or HPV DNA detection in real time in high-risk LA-HNSCC.

Detailed Description
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PRE-MERIDIAN aims to study the kinetics of ctDNA and HPV DNA after standard treatment in high-risk LA-HNSCC patients. This is an important study to understand their role in detecting MRD and determine optimal timing for ctDNA and HPV DNA quantification for future studies in immunotherapy. We hypothesize that HPV DNA (in HPV+) +/- ctDNA detection in plasma after standard therapy may be quantified and monitored as MRD in high risk LA-HNSCC patients. We further hypothesize that detection of MRD in high risk LA-HNSCC after standard therapy may predict recurrence. Finally, we hypothesize that ctDNA time-to-clearance will be longer than 4-6 weeks after the end of treatment in some LA-HNSCC patients and therefore MRD may be further tested at 8-10 weeks after the end of standard therapy

Official Title
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Real-time Detection of ctDNA and/or HPV DNA in High-risk Locally-advanced Head and Neck Squamous Cell Carcinoma (LA-HNSCC): The Pre-MERIDIAN (Molecular Residual Disease Interception in High-risk LA-HNSCC) Study.

Conditions
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Cancer, Head and Neck Squamous Cell Carcinoma, Head and Neck Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytological confirmed LA-HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx. Stage III HPV Positive or Stage III-IV HPV negative. Availability of tumor sample Patients who are candidates for standard definitive treatment defined as: Surgery followed by radiotherapy +/- chemotherapy OR Definite radiotherapy OR Definite chemoradiotherapy. Exclusion Criteria: Early stage HNSCC (I and II) Distant metastatic HNSCC

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| PRE-MERIDIAN<br>Patients with a histological or cytological diagnosis of LA-HNSCC of the oral cavity, oropharynx, hypopharynx, and larynx (stage III HPV positive or stage III-IV HPV negative). Patients who are candidates for standard definitive treatment such as surgery followed by radiotherapy +/- chemotherapy, or definite radiotherapy, or definite chemoradiotherapy. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of high-risk LA-HNSCC patients with successful detection of ctDNA and/or HPV DNA in real time | ctDNA will be detected using Cancer Personalized Profiling by deep Sequencing (CAPP-Seq), a personalized bespoke NGS assay, or a similar approach. HPV DNA will be measured using digital PCR (dPCR) in all plasma samples from HPV+ LA-HNSCC patients included in this study. | Through study completion, up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of presence of ctDNA +/- HPV DNA after standard treatment with shorter relapse-free survival (RFS), as assessed by comparison of baseline ctDNA +/- HPV DNA detection with time to relapse | ctDNA will be detected using Cancer Personalized Profiling by deep Sequencing (CAPP-Seq), a personalized bespoke NGS assay, or a similar approach. HPV DNA will be measured using digital PCR (dPCR) in all plasma samples from HPV+ LA-HNSCC patients included in this study. | Through study completion, up to 2 years | 
| Change in kinetics of ctDNA and/or HPV DNA over time after the end of standard definitive treatment and at recurrence, as assessed by ctDNA/HPV DNA analysis at sequential time points. | To provide preliminary data on the role of ctDNA and HPV DNA on detecting MRD in high-risk LA-HNSCC patients after standard treatment. | Through study completion, up to 2 years | 
| Selection of the best time-point to detect MRD after standard definitive therapy in HNSCC, as assessed by comparison of quantified ctDNA +/- HPV DNA at 4-6 weeks vs 8-10 weeks. | To provide preliminary data on the role of ctDNA and HPV DNA on detecting MRD in high-risk LA-HNSCC patients after standard treatment. | Through study completion, up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kinetics of ctDNA, Kinetics of HPV DNA, High-risk LA-HNSCC, Liquid Biopsy, Head and Neck, Molecular Profiling, Advanced Cancer