Clinical trial NCT04599309: Real-time Detection of ctDNA and/or HPV DNA in High-risk Locally-advanced Head and Neck Squamous Cell Carcinoma
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.
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Cancer
Head and Neck Squamous Cell Carcinoma
Head and Neck Cancer
Keywords: Kinetics of ctDNA
Kinetics of HPV DNA
High-risk LA-HNSCC
Liquid Biopsy
Head and Neck
Molecular Profiling
Advanced Cancer
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Princess Margaret Hospital, Canada
First posted: 2020-10-22
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with a diagnosis of 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.

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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Number of high-risk LA-HNSCC patients with successful detection of ctDNA and/or HPV DNA in real time
timeFrame: Through study completion, up to 2 years
Secondary outcomes:
measure: 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
timeFrame: Through study completion, up to 2 years
measure: 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.
timeFrame: Through study completion, up to 2 years
measure: 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.
timeFrame: Through study completion, up to 2 years
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: Princess Margaret Cancer Centre
name: Lillian Siu
role: PRINCIPAL_INVESTIGATOR
affiliation: Princess Margaret Cancer Centre
name: Scott Bratman
role: PRINCIPAL_INVESTIGATOR
References: