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

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.

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Cancer; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma

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 Type: Observational
• Enrollment (Actual): 35

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, L1M2J2
      • Princess Margaret Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: Princess Margaret Hospital, Canada
• Investigators: Principal Investigator: Lillian Siu, Princess Margaret Cancer Centre; Principal Investigator: Scott Bratman, Princess Margaret Cancer Centre

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2020
• Primary Completion (Actual): March 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: October 18, 2020
• First Submitted That Met QC Criteria: October 18, 2020
• First Posted (Actual): October 22, 2020

Study Record Updates

• Last Update Posted (Actual): May 15, 2023
• Last Update Submitted That Met QC Criteria: May 12, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Advanced Cancer; Liquid Biopsy; Head and Neck; Molecular Profiling; Kinetics of ctDNA; Kinetics of HPV DNA; High-risk LA-HNSCC
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: PRE-MERIDIAN; 20-5804 (Other Identifier: CAPCR ID)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Targeted gene sequencing results, along with limited clinical information that does not identify the patient as an individual, such as age, partial date of birth (year, month), gender, cancer type, and pathology information related to the samples tested, and survival time may be shared with collaborating researchers.

Data from this study can be shared through two types of databases: open-access or controlled-access. An open-access database is publicly accessible and contains limited clinical information and analyses of samples. A controlled-access database contains more detailed clinical information, such as relevant past medical history and the results of prior and ongoing cancer treatments, and analyses of samples, but is only accessible to researchers who sign agreements defining how data may be used. All data will be stripped of all personal identifying information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No