Measurable Residual Disease Detection Using Tumor-Informed ctDNA Surveillance After Curative-Intent Treatment in HPV-Independent Squamous Cell Carcinoma of the Head and Neck (MRD-DUCHESS)

This study will test the ability of a personalized blood test to determine which head and neck cancer patients will have a recurrence after treatment.

Study Overview

• Status: Recruiting
• Conditions: Squamous Cell Carcinoma of Head and Neck
• Intervention / Treatment: Other: Blood Draws and Tissue Sample(s)

Detailed Description

This is a two-arm, prospective, observational study of patients with human papillomavirus (HPV)-independent head and neck squamous cell carcinoma (HNSCC) who are receiving curative-intent treatment. Arm 1 will consist of patients who undergo surgery. Arm 2 will consist of patients who undergo chemoradiotherapy.

The study will test the following hypotheses:

1. That applying a tumor-informed minimal residual disease (MRD) assay after completion of curative-intent treatment will accurately discriminate between patients who will eventually experience recurrence (those are MRD positive) and patients who will remain disease-free (those who are MRD negative). The hypothesis is that patients who have detectable ctDNA following treatment-MRD positive patients-will experience recurrent disease within 2 years, while patients who have no detectable ctDNA-MRD negative patients-will remain disease free at 2 years.
2. That measuring MRD after completion of curative-intent treatment will provide a lead time from detectable to clinical diagnosis of recurrent disease of at least 3 months.

The primary outcome is 2-year DFS in patients with detectable vs no detectable ctDNA two weeks after treatment completion.

The study will accrue 75 patients, who will be followed for a minimum of 2 years.

Subjects will have blood draws before, during and following treatment at regular intervals for testing with the assay (Haystack MRD™)

• Study Type: Observational
• Enrollment (Estimated): 75

Contacts and Locations

• Study Contact: Name: Michael Cheung, MSc, CCRP; Phone Number: 617-573-6060; Email: mcheung0@meei.harvard.edu
• Study Contact Backup: Name: Gyjstina Lumaj; Email: glumaj@meei.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts Eye and Ear
      • Contact: Michael Cheung, MSc, CCRP; Phone Number: 617-573-6060; Email: mcheung0@meei.harvard.edu
      • Contact: Gjystina Lumaj; Email: glumaj@meei.harvard.edu
      • Principal Investigator: Daniel Faden, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with Stage III-IVB mucosal squamous cell carcinoma of the head and neck

Description

Inclusion Criteria:

• Newly diagnosed AJCC 8th edition Stage III-IVB mucosal SCC of the head and neck, which includes tumors arising from the oral cavity, nasal cavity, paranasal sinuses, nasopharynx, oropharynx, hypopharynx, and larynx.
• Available tissue for tumor-informed ctDNA panel creation.
• Definitive treatment with standard of care surgery or chemoradiotherapy is planned to be administered at Massachusetts Eye and Ear Institute (MEEI) or within the Massachusetts General Hospital (MGH) Cancer Center (including but not limited to the Boston, Danvers, and Newton-Wellesley locations).

Exclusion Criteria:

• Patients <18 years of age
• Patients receiving non-standard of care therapy as determined by the clinical investigator
• Participants who have undergone prior surgical resection, excisional biopsy, radiation, and/or chemotherapy for the treatment of HNSCC. Prior incisional biopsies are permitted. Discrepant cases will be reviewed by study PI.
• Participants who are receiving any investigational agents at the time of enrollment.
• Participants with AJCC Stage IVC HNSCC, which includes patients with biopsy-confirmed distant metastatic HNSCC, including but not limited to metastatic spread to the lungs, bones, or liver.
• Active non-HNSCC malignancy.
• Active pregnancy during treatment.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients Receiving only Surgery; Patients in this group will only be those who receive surgery, and does not receive radiographic testing or chemotherapy.	Other: Blood Draws and Tissue Sample(s); All participants on the study, regardless of arm, will be getting blood draws, and tissue samples.
Patients receiving chemoradiotherapy; Newly diagnosed AJCC 8th edition Stage III-IVB mucosal SCC of the head and neck, which includes tumors arising from the oral cavity, nasal cavity, paranasal sinuses, nasopharynx, oropharynx, hypopharynx, and larynx.; Available tissue for tumor-informed ctDNA panel creation.; Definitive treatment with standard of care surgery (arm 1) or chemoradiotherapy (arm 2)	Other: Blood Draws and Tissue Sample(s); All participants on the study, regardless of arm, will be getting blood draws, and tissue samples.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2 Years - Disease Free Survival (DFS)	2-year disease-free survival (DFS) in patients with detectable vs no detectable ctDNA two weeks after treatment completion	2 weeks after treatment completion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2 Years - Overall Survival (OS)	2-year overall survival (OS) in patients with detectable vs no detectable ctDNA two weeks after treatment completion	2 weeks after treatment completion
2 Years - Disease Free Survival (DFS) and Overall Survival (OS)	2-year disease-free survival (DFS) and overall survival (OS) in patients with detectable vs no detectable ctDNA four weeks after treatment completion	4 weeks after treatment completion
2 - Years Disease Free Survival (DFS) and Overall Survival (OS)	2-year disease-free survival (DFS) and overall survival (OS) in patients with detectable vs no detectable ctDNA six weeks after treatment completion	6 week after treatment completion

Collaborators and Investigators

• Sponsor: Massachusetts Eye and Ear Infirmary
• Collaborators: Haystack Oncology, Inc.
• Investigators: Principal Investigator: Daniel Faden, MD, Massachusetts Eye and Ear

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2025
• Primary Completion (Estimated): January 6, 2027
• Study Completion (Estimated): January 6, 2029

Study Registration Dates

• First Submitted: December 9, 2024
• First Submitted That Met QC Criteria: December 19, 2024
• First Posted (Actual): December 20, 2024

Study Record Updates

• Last Update Posted (Actual): May 18, 2025
• Last Update Submitted That Met QC Criteria: May 14, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Neoplastic Processes; Neoplasms, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Carcinoma; Neoplasm, Residual; Carcinoma, Squamous Cell
• Other Study ID Numbers: 2024P002675

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No