Clinical trial NCT06730412: CtDNA Liquid Biopsy for Early Assessment of Residual Disease in HPV-associated Head and Neck Cancer (Clear-HPVca)
Official title: CtDNA Liquid Biopsy for Early Assessment of Residual Disease in HPV-associated Head and Neck Cancer (Clear-HPVca)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HPV Positive Oropharyngeal Squamous Cell Carcinoma
Keywords: MRD
HPV
HPV+ HNSCC
NGS
HPV-DeepSeek
squamous cell carcinoma
head and neck squamous cell carcinoma
circulating tumor DNA
liquid biopsy
minimal residual disease
Lead sponsor: Massachusetts Eye and Ear Infirmary
Sponsor class: OTHER
Collaborators: name: National Institute of Dental and Craniofacial Research (NIDCR)
name: National Institutes of Health (NIH)
name: Massachusetts General Hospital
First posted: 2024-12-12
Enrollment: 103
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: AJCC 8 Stage I-III HPV+ Head and Neck Cancer patient undergoing curative intent surgical resection

Brief summary: The purpose of this study is to test a new liquid biopsy assay for detecting residual disease after surgery in patients with HPV-associated head and neck cancer.

Detailed description: Human papillomavirus associated head and neck squamous cell carcinoma (HPV+HNC) is the most common HPV-associated cancer in the United States. Surgery is a common approach for primary treatment of early-stage HPV+HNC. Many patients who undergo surgery receive adjuvant radiation or chemoradiation therapy to treat potential residual disease, which is currently predicted based on clinicopathologic risk factors including positive margins, extranodal extension, multiple positive lymph nodes, vascular invasion, and lymphatic invasion. However, there are limitations in predicting residual disease based on the use of these features alone - the use of clinicopathologic risk factors for prediction is non-standardized and has poor individualized predictive and prognostic capacity. Currently, there are no established biomarkers to predict residual disease.

Circulating tumor DNA (ctDNA) is an emerging minimally invasive prognostic biomarker, for detecting molecular residual disease (MRD) and predicting recurrence in multiple solid cancers. Prospective trials in cancers such as colorectal cancer have demonstrated not only strong Disease Free Survival (DFS) prognostic capacity but also Overall Survival (OS). Previous studies have demonstrated that HPV+HNCs release circulating tumor HPV DNA (ctHPVDNA) into the blood where it serves as an accurate real-time biomarker of disease status after surgery. In patients without pathological risk factors, ctHPVDNA is rapidly cleared after surgery. In patients with residual disease, ctHPVDNA remains elevated after surgery. However, initial studies have showed that patients with microscopic levels of residual disease are often not detected by current approaches using droplet digital PCR (ddPCR), suggesting significantly more sensitive assays are necessary.

HPV-DeepSeek is an HPV whole genome next-generation sequencing assay which is significantly more sensitive than ddPCR-based approaches. We aim to conduct a prospective observational cohort study of HPV+HNC patients treated with curative intent surgery to test the primary hypothesis that patients with MRD detection after surgery will have inferior 2-year DFS and OS and the secondary hypothesis that patients with MRD detection after treatment completion (surveillance) will have inferior 2-year DFS and OS.

Eligibility criteria: Inclusion Criteria:

* Greater than or equal to 18 years of age
* Newly diagnosed, untreated, histologically confirmed HPV-associated head and neck cancer
* Scheduled for curative intent resection as primary treatment
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

Exclusion Criteria:

* Not meeting all inclusion criteria
* Pregnant
* Receiving treatment for concurrent second maligancy

Primary outcomes:
measure: Disease free survival
timeFrame: 2 years
measure: Overall survival
timeFrame: 2 years
Secondary outcomes:
measure: Disease free survival
timeFrame: 2 years
measure: Overall survival
timeFrame: 2 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Department of Otolaryngology - Head and Neck Surgery, Massachusetts Eye and Ear Infirmary
state: Massachusetts
Study officials:
References: