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

Sponsor

University Health Network, Toronto (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04599309

Collaborator

Princess Margaret Hospital, Canada (Other)

Enrollment

Location

25.5

Anticipated Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Cancer Head and Neck Squamous Cell Carcinoma Head and Neck Cancer

Detailed Description

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

Study Design

Study Type:

Observational

Actual Enrollment :

35 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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.

Actual Study Start Date :

Oct 15, 2020

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
PRE-MERIDIAN 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.

Outcome Measures

Primary Outcome Measures

Number of high-risk LA-HNSCC patients with successful detection of ctDNA and/or HPV DNA in real time [Through study completion, up to 2 years]
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.

Secondary Outcome Measures

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 [Through study completion, up to 2 years]
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.
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. [Through study completion, up to 2 years]
To provide preliminary data on the role of ctDNA and HPV DNA on detecting MRD in high-risk LA-HNSCC patients after standard treatment.
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. [Through study completion, up to 2 years]
To provide preliminary data on the role of ctDNA and HPV DNA on detecting MRD in high-risk LA-HNSCC patients after standard treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.