HPV Positive Oropharyngeal Squamous Cell CarcinomaClear-HPVcaNCT06730412
ctDNA Liquid Biopsy for Early Assessment of Residual Disease in HPV-associated Head and Neck Cancer (Clear-HPVca)
An observational study of HPV Positive Oropharyngeal Squamous Cell Carcinoma, run by Massachusetts Eye and Ear Infirmary at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HPV Positive Oropharyngeal Squamous Cell Carcinoma
- How many people
- 103 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2020to 31 Oct 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: AJCC 8 Stage I-III HPV+ Head and Neck Cancer patient undergoing curative intent surgical resection
Who may be able to join
- 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
Who cannot join
- Not meeting all inclusion criteria
- Pregnant
- Receiving treatment for concurrent second malignancy
Trial locations and contacts
1 site in 1 country.
United States1 site
Department of Otolaryngology - Head and Neck Surgery, Massachusetts Eye and Ear Infirmary
Boston, Massachusetts, 02114
About this study
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.
Read the 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. The investigators 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.
- 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
- Medical subject headings
- Carcinoma, Squamous Cell, Squamous Cell Carcinoma of Head and Neck, Neoplasm, Residual
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| HPV-associated head and neck cancer patients treated with surgery | AJCC 8 Stage I-III HPV+ head and neck cancer patients treated with curative intent surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease free survival
Disease free survival in patients with versus without minimal residual disease detection after surgery
Measured: 2 years
Overall survival
Overall survival in patients with versus without minimal residual disease detection after surgery
Measured: 2 years
Secondary outcomes (2)
Disease free survival
Disease free survival in patients with versus without minimal residual disease detection after treatment completion
Measured: 2 years
Overall survival
Overall survival in patients with versus without minimal residual disease detection after treatment completion
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2024
- Study start1 Aug 2020
- Primary completion31 Oct 2024
- Study completion31 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HPV Positive Oropharyngeal Squamous Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts Eye and Ear Infirmary
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH), Massachusetts General Hospital
- Responsible party
- Principal investigator, Daniel L. Faden, MD, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06730412
- Sponsor's protocol ID
- 18-653
- Other IDs
- R03DE030550
- Acronym
- Clear-HPVca
- Status last verified
- Dec 2024
- First submitted
- 9 Dec 2024
- Last updated
- 4 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ctDNA Liquid Biopsy for Early Assessment of Residual Disease in HPV-associated Head and Neck Cancer (Clear-HPVca)
- ClinicalTrials.gov ID
- NCT06730412
- Acronym / sponsor ID
- Clear-HPVca / 18-653
- Keywords
- MRD, HPV, HPV+ HNSCC, NGS, HPV-DeepSeek, squamous cell carcinoma, head and neck squamous cell carcinoma, circulating tumor DNA
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 103 participants (actual)
- Lead sponsor
- Massachusetts Eye and Ear InfirmaryUniversity, hospital or other
- Collaborators
- National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH), Massachusetts General Hospital
- Study start
- 1 Aug 2020 (actual)
- Primary completion
- 31 Oct 2024 (actual)
- Study completion
- 31 Oct 2024 (actual)
- First posted
- 12 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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. The investigators 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HPV-associated head and neck cancer patients treated with surgery | – | –AJCC 8 Stage I-III HPV+ head and neck cancer patients treated with curative intent surgery |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- AJCC 8 Stage I-III HPV+ Head and Neck Cancer patient undergoing curative intent surgical resection
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (3 listed)
- Not meeting all inclusion criteria
- Pregnant
- Receiving treatment for concurrent second malignancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Disease free survival
Time frame: 2 years
Disease free survival in patients with versus without minimal residual disease detection after surgery
Overall survival
Time frame: 2 years
Overall survival in patients with versus without minimal residual disease detection after surgery
2 secondary outcomes
Disease free survival
Time frame: 2 years
Overall survival
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HPV Positive Oropharyngeal Squamous Cell Carcinoma, run by Massachusetts Eye and Ear Infirmary at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease free survival (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2025.