Squamous Cell Carcinoma of the OropharynxPhase 2HN001NCT05962242
HPV DNA-Guided Radiotherapy De-intensification of Head and Neck Squamous Cell Carcinoma
A Phase 2 study testing Radiation Therapy in people with Squamous Cell Carcinoma of the Oropharynx, run by University of Virginia at 5 sites in United States.
Trial summary
The study will evaluate the safety and effectiveness of a lower than standard dose of radiation for definitive or adjuvant treatment of head and neck squamous cell carcinomas. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Cell Carcinoma of the Oropharynx
- What is being tested?
- Radiation Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 5 sitesUnited States
- Study dates
- 28 Jun 2024to 1 Nov 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
Who may be able to join
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, ≥ 18 years of age
- Pathologically proven diagnosis of squamous cell carcinoma of the oropharynx of any AJCC 8th edition stage.
- Eligible for and planning to receive definitive treatment or adjuvant treatment with radiotherapy.
- Participants who are receiving concurrent systemic anticancer therapy (e.g. chemotherapy or immunotherapy) for oropharyngeal cancer are eligible.
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- For participants with T1-2 and N0 disease, chemotherapy is not required for eligibility. Participants may or may not receive chemotherapy per physician discretion.
- For participants with T3-4 and/or N+ disease, chemotherapy is required for eligibility.
- Participants may receive investigational agents with prior approval from the Principal Investigator.
- ECOG Performance Status of 0-2.
- p16 positive HPV as determined by NavDx and immunohistochemistry
- For females of reproductive potential: agreement to use adequate contraception during radiation treatment and for 6 months (or more if applicable based on other medications) after the end of radiation treatment.
Who cannot join
- Evidence of distant metastatic disease
- Prior history of radiotherapy to the head and/or neck
- Had surgery for oropharyngeal cancer within 8 months of enrollment unless it was an incomplete oncologic surgery. Participant is eligible if the gross tumor was not completely removed.
- Diagnosis of T3-4 and/or N+ disease with no plans to receive concurrent chemotherapy.
- Diagnosis of a current or prior invasive malignancy (except non-melanoma skin cancer) unless the participant has been disease free for at least 3 years.
- Participant is a prisoner
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- Known contraindications to head and neck radiation therapy such as ataxia telangiectasia or scleroderma.
- Pregnancy or lactation
- Active or severe co-morbidities as defined by the following:
- Unstable angina and/or congestive heart failure requiring hospitalization up to 180 days before registration
- Transmural myocardial infarction up to 180 days before registration
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
- Hepatic insufficiency as determined by the treating clinician resulting in clinical jaundice and/or coagulation effects or severe liver dysfunction.
- Acquired immune deficiency syndrome (AIDS) based upon current CDC definition. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be slightly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients.
- Tobacco smoking history of 10 pack years or greater, or ≥ 20 pack years if smoking cessation occurred at least 1 year prior to enrollment
- Current use of antineoplastic drugs for other malignancies.
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
United States5 sites, 5 recruiting
- Recruiting
University of Virginia
Charlottesville, Virginia, 22908
Song W, 4342430008, UVARADONCClinicalTrials@uvahealth.org
Chris McLaughlin, M.D.
- Recruiting
Miami Cancer Institute
Miami, Florida, 33176
Noah Kalman, M.D., (786) 596-2000, noahk@baptisthealth.net
Noah Kalman, MD
- Not yet recruiting
Eastern Virginia Medical School
Norfolk, Virginia, 23507
Edwin Crandley, M.D.
- Not yet recruiting
Bon Secours
Richmond, Virginia, 23114
Chris Chipko, MD
- Recruiting
Virginia Commonwealth University
Richmond, Virginia, 23284
Shiyu Song, M.D., masseyhn@vcu.edu
About this study
Official title: Circulating Tumor Modified HPV DNA-Guided Radiotherapy De-intensification of the Elective Neck (RaDEN) in Squamous Cell Carcinoma of the Head and Neck
The study will evaluate the safety and effectiveness of a lower than standard dose of radiation for definitive or adjuvant treatment of head and neck squamous cell carcinomas.
Read the detailed description
In squamous cell carcinomas of the head and neck, regional recurrence is rare within lymph node stations treated with elective radiation. However, radiotherapy to the neck is toxic, and leads to a variety of unpleasant side effects, especially coupled with concurrent systemic therapy. There is growing evidence from previous studies showing that lower radiation doses may be adequate in preventing locoregional recurrence of disease. The hypothesis is that lower dose of radiation will have equal effectiveness but less toxicity than standard approaches for the treatment of squamous cell carcinomas of the head and neck.
The study evaluates the effectiveness and safety of reduced dose radiotherapy for definitive and adjuvant treatment of Human papillomavirus (HPV) positive oropharyngeal squamous cell carcinomas.
Participants will be treated with a radiation therapy regimen that has a lower dose to less tissue area (dose and volume de-escalation) than standard of care radiation therapy. The dosing will be determined by whether concurrent chemotherapy will be given, results from on treatment HPV blood test called NavDx, physical exam, and imaging. On treatment NavDx results indicating a slow (non-rapid) response to the treatment will receive an additional boost of radiation. Routine NavDx testing will be performed to assess treatment response and recurrence. Participants will also be asked to complete surveys about overall health and wellbeing.
- Being tested
- Radiation Therapy
- Keywords
- Radiation Therapy, Radiotherapy, Head Cancer, Neck Cancer, Low Dose Radiation, HPV
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Radiation TherapyRadiation
External Beam Radiation to Head and Neck
| Study group | Role | What they receive |
|---|---|---|
| Reduce Dose without Concurrent Chemotherapy Non- Rapid Responder | Experimental | A reduced dose regimen of 24 Gy in 12 fractions to gross disease and intermediate nodes. Then 36 Gy in 18 fractions to entire volume. Non-responders will receive an additional boost of 10 Gy in 5 fractions to entire volume. Receives: Radiation: Radiation Therapy |
| Reduce Dose with Concurrent Chemotherapy Non-Rapid Responder | Experimental | A reduced dose regimen of 24 Gy in 12 fractions to gross disease and intermediate nodes. Then 30 Gy in 15 fractions to entire volume. Non-responders will receive an additional boost of 10 Gy in 5 fractions to entire volume. Receives: Radiation: Radiation Therapy |
| Reduce Dose without Concurrent Chemotherapy Rapid Responder | Experimental | A reduced dose regimen of 24 Gy in 12 fractions to gross disease and intermediate nodes. Then 36 Gy in 18 fractions to entire volume. Receives: Radiation: Radiation Therapy |
| Reduce Dose with Concurrent Chemotherapy Rapid Responder | Experimental | A reduced dose regimen of 24 Gy in 12 fractions to gross disease and intermediate nodes. Then 30 Gy in 15 fractions to entire volume. Receives: Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the disease control of participants who receive dose and volume-de-escalated radiotherapy to the neck, guided by treatment response through circulating tumor-modified HPV DNA testing
Incidence of disease free survival as measured by circulating HPV on Nav Dx blood tests.
Measured: up to 2 years after radiotherapy
Secondary outcomes (3)
To assess safety for treatment with reduced dose and volume-de-escalated radiotherapy to the neck
Incidence of grade 3 (or greater) adverse events as defined by the CTCAE v5.0
Measured: Evaluated through 6 months and 1 year post- radiation.
To estimate quality of life of participants who receive reduced dose and volume-de-escalated radiotherapy to the neck
Quality of life as determined by the EORTC H\&N35. Questions are scaled from 1-4 with 1 meaning the symptom/problem was not experienced and 4 meaning the symptom/problem was experienced at a high level.
Measured: up to 2 years after radiotherapy
To estimate quality of life of participants who receive reduced dose and volume-de-escalated radiotherapy to the neck
Quality of life as determined by the EORTC QLQ-C30. Majority of questions are scaled from 1-4 with 1 meaning the symptom/problem was not experienced and 4 meaning the symptom/problem was experienced at a high level. Two questions are scaled from 1-7 with 1 meaning very poor (worse outcome) and 7 meaning excellent (best outcome).
Measured: up to 2 years after radiotherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2023
- Study start28 Jun 2024
- Primary completion1 Nov 2027 (estimated)
- Study completion1 Nov 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Squamous Cell Carcinoma of the OropharynxStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Participants on this study will undergo a reduced dose regimen starting with a boost to gross disease of 24 Gy, then 30-36 Gy to entire volume based on the plan for concurrent chemotherapy. Non-responders will receive a boost to the entire volume for an additional 10 Gy.
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Christopher McLaughlin, MD, University of Virginia
- Investigators
- Chris McLaughlin, M.D., Principal investigator, UVA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05962242
- Sponsor's protocol ID
- HSR220263
- Acronym
- HN001
- Status last verified
- Feb 2026
- First submitted
- 30 Jun 2023
- Last updated
- 5 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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 5 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Circulating Tumor Modified HPV DNA-Guided Radiotherapy De-intensification of the Elective Neck (RaDEN) in Squamous Cell Carcinoma of the Head and Neck
- ClinicalTrials.gov ID
- NCT05962242
- Acronym / sponsor ID
- HN001 / HSR220263
- Keywords
- Radiation Therapy, Radiotherapy, Head Cancer, Neck Cancer, Low Dose Radiation, HPV
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Study start
- 28 Jun 2024 (actual)
- Primary completion
- 1 Nov 2027 (estimated)
- Study completion
- 1 Nov 2029 (estimated)
- First posted
- 27 Jul 2023 (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 study will evaluate the safety and effectiveness of a lower than standard dose of radiation for definitive or adjuvant treatment of head and neck squamous cell carcinomas.
Detailed description
In squamous cell carcinomas of the head and neck, regional recurrence is rare within lymph node stations treated with elective radiation. However, radiotherapy to the neck is toxic, and leads to a variety of unpleasant side effects, especially coupled with concurrent systemic therapy. There is growing evidence from previous studies showing that lower radiation doses may be adequate in preventing locoregional recurrence of disease. The hypothesis is that lower dose of radiation will have equal effectiveness but less toxicity than standard approaches for the treatment of squamous cell carcinomas of the head and neck.
The study evaluates the effectiveness and safety of reduced dose radiotherapy for definitive and adjuvant treatment of Human papillomavirus (HPV) positive oropharyngeal squamous cell carcinomas.
Participants will be treated with a radiation therapy regimen that has a lower dose to less tissue area (dose and volume de-escalation) than standard of care radiation therapy. The dosing will be determined by whether concurrent chemotherapy will be given, results from on treatment HPV blood test called NavDx, physical exam, and imaging. On treatment NavDx results indicating a slow (non-rapid) response to the treatment will receive an additional boost of radiation. Routine NavDx testing will be performed to assess treatment response and recurrence. Participants will also be asked to complete surveys about overall health and wellbeing.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Participants on this study will undergo a reduced dose regimen starting with a boost to gross disease of 24 Gy, then 30-36 Gy to entire volume based on the plan for concurrent chemotherapy. Non-responders will receive a boost to the entire volume for an additional 10 Gy.
| Arm | Type | Receives |
|---|---|---|
| Reduce Dose without Concurrent Chemotherapy Non- Rapid Responder | Experimental | Radiation: Radiation TherapyA reduced dose regimen of 24 Gy in 12 fractions to gross disease and intermediate nodes. Then 36 Gy in 18 fractions to entire volume. Non-responders will receive an additional boost of 10 Gy in 5 fractions to entire volume. |
| Reduce Dose with Concurrent Chemotherapy Non-Rapid Responder | Experimental | Radiation: Radiation TherapyA reduced dose regimen of 24 Gy in 12 fractions to gross disease and intermediate nodes. Then 30 Gy in 15 fractions to entire volume. Non-responders will receive an additional boost of 10 Gy in 5 fractions to entire volume. |
| Reduce Dose without Concurrent Chemotherapy Rapid Responder | Experimental | Radiation: Radiation TherapyA reduced dose regimen of 24 Gy in 12 fractions to gross disease and intermediate nodes. Then 36 Gy in 18 fractions to entire volume. |
| Reduce Dose with Concurrent Chemotherapy Rapid Responder | Experimental | Radiation: Radiation TherapyA reduced dose regimen of 24 Gy in 12 fractions to gross disease and intermediate nodes. Then 30 Gy in 15 fractions to entire volume. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, ≥ 18 years of age
- Pathologically proven diagnosis of squamous cell carcinoma of the oropharynx of any AJCC 8th edition stage.
- Eligible for and planning to receive definitive treatment or adjuvant treatment with radiotherapy.
Key exclusion criteria (17 listed)
- Evidence of distant metastatic disease
- Prior history of radiotherapy to the head and/or neck
- Had surgery for oropharyngeal cancer within 8 months of enrollment unless it was an incomplete oncologic surgery. Participant is eligible if the gross tumor was not completely removed.
- Diagnosis of T3-4 and/or N+ disease with no plans to receive concurrent chemotherapy.
- Diagnosis of a current or prior invasive malignancy (except non-melanoma skin cancer) unless the participant has been disease free for at least 3 years.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Radiation TherapyExternal Beam Radiation to Head and Neck | Radiation | Reduce Dose with Concurrent Chemotherapy Non-Rapid Responder, Reduce Dose with Concurrent Chemotherapy Rapid Responder, Reduce Dose without Concurrent Chemotherapy Non- Rapid Responder, Reduce Dose without Concurrent Chemotherapy Rapid Responder |
Primary outcome
To assess the disease control of participants who receive dose and volume-de-escalated radiotherapy to the neck, guided by treatment response through circulating tumor-modified HPV DNA testing
Time frame: up to 2 years after radiotherapy
Incidence of disease free survival as measured by circulating HPV on Nav Dx blood tests.
3 secondary outcomes
To assess safety for treatment with reduced dose and volume-de-escalated radiotherapy to the neck
Time frame: Evaluated through 6 months and 1 year post- radiation.
To estimate quality of life of participants who receive reduced dose and volume-de-escalated radiotherapy to the neck
Time frame: up to 2 years after radiotherapy
To estimate quality of life of participants who receive reduced dose and volume-de-escalated radiotherapy to the neck
Time frame: up to 2 years after radiotherapy
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2026.
- 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.
Chris McLaughlin, M.D. principal investigator
UVA
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Radiation Therapy in people with Squamous Cell Carcinoma of the Oropharynx, run by University of Virginia at 5 sites 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 12 inclusion and 17 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: looking for participants now, as of the sponsor's last update on 5 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Song W (434-243-0008, UVARADONCClinicalTrials@uvahealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess the disease control of participants who receive dose and volume-de-escalated radiotherapy to the neck, guided by treatment response through circulating tumor-modified HPV DNA testing (time frame: up to 2 years after radiotherapy). 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 5 Feb 2026.