OPSCCPhase 2NCT06759155
Phase II Clinical Trial of De-Intensified Therapy in Human Papilloma Virus (HPV) Associated Oropharyngeal Squamous Cell Carcinoma
A Phase 2 study testing de-intensified radiation in people with OPSCC and Oropharyngeal Squamous Cell Carcinoma (SCC), run by University of Vermont Medical Center.
Trial summary
HPV-associated Oropharyngeal Squamous Cell Carcinoma (OPSCC) is a type of cancer that affects parts of the throat, like the tonsils and the base of the tongue. The treatments for OPSCC, which may include surgery, radiation, and chemotherapy, often cause serious side effects, such as loss of taste, dry mouth, and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- OPSCC, Oropharyngeal Squamous Cell Carcinoma (SCC), HPV Associated Cancers
- What is being tested?
- de-intensified radiation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- No sites listed yet
- Study dates
- Jan 2025to Jan 2030
- 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
- Histologically confirmed or suspected HPV associated squamous cell carcinoma of the oropharynx.
- p16 immunohistochemistry is the surrogate marker for HPV positivity and will be scored as positive if there is strong and diffuse nuclear and cytoplasmic staining present in greater than 70% of the tumor specimen. (A negative result excludes the patient from the trial)
- In the case of equivocal p16, High Risk HPV (HR HPV), In-Situ Hybridization (ISH) / Polymerase Chain Reaction (PCR) may be performed to determine HPV positivity
- AJCC TNM 7th edition stage T1-T3, N0-N2b (or AJCC TNM 8th edition stage T1-T3 N0-N1) disease.
- Staging will be based on cross sectional imaging investigations and clinical exam.
- Patients who initially have an unknown primary but subsequently have a primary site identified on pathology after surgical resection may be included in the study.
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- Multidisciplinary team decision to treat with primary transoral resection and neck dissection.
- Patients considered fit for surgery and adjuvant therapy.
- Aged 18 or over.
- Written informed consent provided.
Who cannot join
- HPV negative squamous cell carcinomas of the head and neck
- T4 and/or T1-T3 tumors where transoral surgery is considered not feasible or there is a high likelihood of positive margins.
- AJCC TNM 7th edition N2c-N3 nodal disease (or AJCC TNM 8th edition N2-N3 nodal disease) or high likelihood of gross extranodal extension.
- Patients for whom transoral surgery and neck dissection is not considered the primary treatment modality.
- Distant metastatic disease as determined by routine pre-operative staging radiological investigations e.g. CT thorax and upper abdomen or PET CT.
- Women who are pregnant or breastfeeding
- Prior history of radiation to head and neck
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
HPV-associated Oropharyngeal Squamous Cell Carcinoma (OPSCC) is a type of cancer that affects parts of the throat, like the tonsils and the base of the tongue. The treatments for OPSCC, which may include surgery, radiation, and chemotherapy, often cause serious side effects, such as loss of taste, dry mouth, and long-term problems with swallowing. These side effects can lower patients' quality of life and make it difficult for them to eat and speak normally.
This study aims to explore whether using lower doses of radiation after surgery can help improve long-term swallowing function in patients with HPV-positive OPSCC. By doing this, the study team hopes to reduce treatment-related side effects while maintaining good cancer control.
- Being tested
- de-intensified radiation
- Keywords
- radiation, de-intensify
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
de-intensified radiationRadiation
Adjuvant radiation will be administered on a de-intensified schedule.
| Study group | Role | What they receive |
|---|---|---|
| Very Low Risk | No intervention | Patients with T1-T2 tumors which exhibit no adverse histological features (must have all of the following: negative margins, no perineural invasion or vascular invasion, 1 or fewer lymph nodes with metastasis ≤3 cm in size, negative for extranodal extension). Patients in this group will not receive any adjuvant treatment per standard of care. |
| Low Risk | Experimental | Patients with T1-T2 tumors which exhibit no adverse histological features (must have all of the following: negative margins, no perineural invasion or vascular invasion), 2 lymph nodes with metastasis and/or lymph node metastasis 3.1-4cm in size, negative for extranodal extension, not "positive" or "intermediate" HPV ctDNA post-surgery. Patients in this group will not receive any adjuvant treatment. This is a de-intensified treatment, since NCCN guidelines recommend adjuvant radiation 60Gy for patients with a nodal metastasis greater than 3 cm in size or if there are multiple positive nodes Receives: Radiation: de-intensified radiation |
| Intermediate Risk | Experimental | Patients with any of the following - T3 tumors or T1-T2 tumors with additional risk factors (perineural invasion or vascular invasion), lymph node involvement greater than 4cm in size or with minimal extranodal extension (1-2mm), 3 or more lymph nodes with metastasis, "intermediate" or "positive" HPVctDNA post-surgery. Patients in this group will receive adjuvant radiation therapy at a de-intensified dose of 50Gy (as opposed to standard dose of 60Gy). Receives: Radiation: de-intensified radiation |
| High Risk | Experimental | Patients with tumors of any T or any N stage, which exhibit grossly positive margins or extensive extranodal extension. Patients in this group will receive standard of care treatment (per physician discretion, usually involves chemoradiation). Treatment for this group is not part of the protocol. Patient can elect to enroll on the imaging/HPV ctDNA surveillance component of the trial. Since this is not a de-intensified regimen, every effort will be made to reduce the number of patients in the high-risk category through careful baseline clinical exam and evaluation of imaging. In patients whom there is a concern for gross extranodal extension or that surgery will result in a grossly positive margin, they will be recommended to undergo a non-surgical route in order to avoid triple modality therapy. Receives: Radiation: de-intensified radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess oncologic outcomes of a de-intensified post-surgical adjuvant treatment by measuring overall survival.
Overall survival will be monitored.
Measured: from enrollment to 5 year follow-up
Safety and tolerability
The study will use the CTCAE version 5.0 for reporting of non-hematologic adverse events.
Measured: from enrollment to 5 year follow-up
Assess oncologic outcomes of a de-intensified post-surgical adjuvant treatment by measuring progression free survival.
Assess oncologic outcomes of a de-intensified post-surgical adjuvant treatment by measuring progression free survival.
Measured: from enrollment to 5 year follow-up
Assess oncologic outcomes of a de-intensified post-surgical adjuvant treatment by measuring locoregional control.
Locoregional control (LRC) is defined as time from treatment initiation to local or regional recurrence
Measured: from enrollment to 5 year follow-up
Secondary outcomes (1)
Evaluate how changes in serum HPV ctDNA are associated\ with HPV-positive OPSCC recurrence
ctDNA will be measured at baseline and at several points during follow-up. The sensitivity, specificity and concordance of the HPV ctDNA results in relation to the clinical and pathologic disease status (presence/absence) will be corelated.
Measured: from enrollment to 5 year follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2025
- Study startJan 2025 (estimated)
- Primary completionJan 2030 (estimated)
- Study completionJan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for OPSCCStudies 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be stratified into 4 groups depending on their risk factors. Groups A and be will not receive radiation (de-intensified), group C will receive a de-intensified level of radiation, group D will receive standard of care radiation (not de-intensified).
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Vermont Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mirabelle Sajisevi, University of Vermont Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06759155
- Sponsor's protocol ID
- STUDY00003257/UVMCC2405
- Status last verified
- Nov 2024
- First submitted
- 19 Dec 2024
- Last updated
- 6 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Clinical Trial of De-Intensified Therapy in Human Papilloma Virus (HPV) Associated Oropharyngeal Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT06759155
- Acronym / sponsor ID
- STUDY00003257/UVMCC2405
- Keywords
- radiation, de-intensify
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University of Vermont Medical CenterUniversity, hospital or other
- Study start
- Jan 2025 (estimated)
- Primary completion
- Jan 2030 (estimated)
- Study completion
- Jan 2030 (estimated)
- First posted
- 6 Jan 2025 (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.
HPV-associated Oropharyngeal Squamous Cell Carcinoma (OPSCC) is a type of cancer that affects parts of the throat, like the tonsils and the base of the tongue. The treatments for OPSCC, which may include surgery, radiation, and chemotherapy, often cause serious side effects, such as loss of taste, dry mouth, and long-term problems with swallowing. These side effects can lower patients' quality of life and make it difficult for them to eat and speak normally.
This study aims to explore whether using lower doses of radiation after surgery can help improve long-term swallowing function in patients with HPV-positive OPSCC. By doing this, the study team hopes to reduce treatment-related side effects while maintaining good cancer control.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Patients will be stratified into 4 groups depending on their risk factors. Groups A and be will not receive radiation (de-intensified), group C will receive a de-intensified level of radiation, group D will receive standard of care radiation (not de-intensified).
| Arm | Type | Receives |
|---|---|---|
| Very Low Risk | No intervention | –Patients with T1-T2 tumors which exhibit no adverse histological features (must have all of the following: negative margins, no perineural invasion or vascular invasion, 1 or fewer lymph nodes with metastasis ≤3 cm in size, negative for extranodal extension). Patients in this group will not receive any adjuvant treatment per standard of care. |
| Low Risk | Experimental | Radiation: de-intensified radiationPatients with T1-T2 tumors which exhibit no adverse histological features (must have all of the following: negative margins, no perineural invasion or vascular invasion), 2 lymph nodes with metastasis and/or lymph node metastasis 3.1-4cm in size, negative for extranodal extension, not "positive" or "intermediate" HPV ctDNA post-surgery. Patients in this group will not receive any adjuvant treatment. This is a de-intensified treatment, since NCCN guidelines recommend adjuvant radiation 60Gy for patients with a nodal metastasis greater than 3 cm in size or if there are multiple positive nodes |
| Intermediate Risk | Experimental | Radiation: de-intensified radiationPatients with any of the following - T3 tumors or T1-T2 tumors with additional risk factors (perineural invasion or vascular invasion), lymph node involvement greater than 4cm in size or with minimal extranodal extension (1-2mm), 3 or more lymph nodes with metastasis, "intermediate" or "positive" HPVctDNA post-surgery. Patients in this group will receive adjuvant radiation therapy at a de-intensified dose of 50Gy (as opposed to standard dose of 60Gy). |
| High Risk | Experimental | Radiation: de-intensified radiationPatients with tumors of any T or any N stage, which exhibit grossly positive margins or extensive extranodal extension. Patients in this group will receive standard of care treatment (per physician discretion, usually involves chemoradiation). Treatment for this group is not part of the protocol. Patient can elect to enroll on the imaging/HPV ctDNA surveillance component of the trial. Since this is not a de-intensified regimen, every effort will be made to reduce the number of patients in the high-risk category through careful baseline clinical exam and evaluation of imaging. In patients whom there is a concern for gross extranodal extension or that surgery will result in a grossly positive margin, they will be recommended to undergo a non-surgical route in order to avoid triple modality therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Histologically confirmed or suspected HPV associated squamous cell carcinoma of the oropharynx.
- p16 immunohistochemistry is the surrogate marker for HPV positivity and will be scored as positive if there is strong and diffuse nuclear and cytoplasmic staining present in greater than 70% of the tumor specimen. (A negative result excludes the patient from the trial)
- In the case of equivocal p16, High Risk HPV (HR HPV), In-Situ Hybridization (ISH) / Polymerase Chain Reaction (PCR) may be performed to determine HPV positivity
- AJCC TNM 7th edition stage T1-T3, N0-N2b (or AJCC TNM 8th edition stage T1-T3 N0-N1) disease.
- Staging will be based on cross sectional imaging investigations and clinical exam.
Key exclusion criteria (7 listed)
- HPV negative squamous cell carcinomas of the head and neck
- T4 and/or T1-T3 tumors where transoral surgery is considered not feasible or there is a high likelihood of positive margins.
- AJCC TNM 7th edition N2c-N3 nodal disease (or AJCC TNM 8th edition N2-N3 nodal disease) or high likelihood of gross extranodal extension.
- Patients for whom transoral surgery and neck dissection is not considered the primary treatment modality.
- Distant metastatic disease as determined by routine pre-operative staging radiological investigations e.g. CT thorax and upper abdomen or PET CT.
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 |
|---|---|---|
| de-intensified radiationAdjuvant radiation will be administered on a de-intensified schedule. | Radiation | High Risk, Intermediate Risk, Low Risk |
Primary outcome
Assess oncologic outcomes of a de-intensified post-surgical adjuvant treatment by measuring overall survival.
Time frame: from enrollment to 5 year follow-up
Overall survival will be monitored.
Safety and tolerability
Time frame: from enrollment to 5 year follow-up
The study will use the CTCAE version 5.0 for reporting of non-hematologic adverse events.
Assess oncologic outcomes of a de-intensified post-surgical adjuvant treatment by measuring progression free survival.
Time frame: from enrollment to 5 year follow-up
Assess oncologic outcomes of a de-intensified post-surgical adjuvant treatment by measuring progression free survival.
Assess oncologic outcomes of a de-intensified post-surgical adjuvant treatment by measuring locoregional control.
Time frame: from enrollment to 5 year follow-up
Locoregional control (LRC) is defined as time from treatment initiation to local or regional recurrence
1 secondary outcome
Evaluate how changes in serum HPV ctDNA are associated\ with HPV-positive OPSCC recurrence
Time frame: from enrollment to 5 year follow-up
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 6 Jan 2025.
- Individual participant dataSharing planned: Undecided
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Rimegepant-Sensitized Neoadjuvant Chemoimmunotherapy for Oral or Oropharyngeal Squamous Cell Carcinoma
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing de-intensified radiation in people with OPSCC and Oropharyngeal Squamous Cell Carcinoma (SCC), run by University of Vermont Medical Center.
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 10 inclusion and 7 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: opening soon, as of the sponsor's last update on 6 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
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 Mirabelle Sajisevi, MD ((802) 847-4535, Mirabelle.sajisevi@uvmhealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assess oncologic outcomes of a de-intensified post-surgical adjuvant treatment by measuring overall survival. (time frame: from enrollment to 5 year follow-up). The study lists 4 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 6 Jan 2025; AzTrials last refreshed its copy on 8 Nov 2026.