Head and Neck CancerPhase 1/2NCT07213934
Phase I/ II Trial Combining PD-1 Inhibition and Neoadjuvant Proton or Photon Radiation Therapy in Recurrent Head and Neck Squamous Cell Carcinoma
A Phase 1/2 study testing Proton therapy and Pembrolizumab in people with Head and Neck Cancer and Recurrent Head and Neck Squamous Cell Carcinoma, run by University of Cincinnati at 1 site in United States.
Trial summary
The purpose of the Phase I study is to see if it is safe to use X-ray photon radiation (XRT) and proton radiation (PT) before surgery in patients with recurrent head and neck squamous cell carcinoma (rHNSCC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer, Recurrent Head and Neck Squamous Cell Carcinoma
- What is being tested?
- Proton therapy and Pembrolizumab
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Oct 2025to Dec 2031
- Phase
- Phase 1/2
- 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
- Patients must have histologically or cytologically confirmed recurrent head and neck squamous cell carcinoma including oral cavity, laryngeal, hypopharyngeal, or oropharyngeal (HPV-) SCC.
- Patients must be a candidate for salvage surgical resection.
- Patients must have failed prior RT >6 months prior to recurrence with at least 30 Gy delivered to the current target volume.
- Disease must be limited to a single site or adjacent sites that can be treated in a single contiguous target volume for which the maximum total tumor dimension (GTV) must be <7 cm.
- Patients must have a CPS PD-L1 of ≥1%. This may be tested on a new biopsy or archival tissue.
- Age ≥18 years.
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- ECOG performance status ≤1 (or Karnofsky ≥70%, see Appendix A).
- Patients must have adequate organ and marrow function as defined below:
- Platelets ≥100,000/mcL Total bilirubin ≤ institutional upper limit of normal (ULN) AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN Creatinine ≤ 1.5x institutional upper limit of normal (ULN) OR glomerular filtration rate (GFR) ≥30 mL/min/1.73 m2 (see Appendix B).
- Archival tissue must be available for baseline analysis. Either a tumor block or at least 20 slides must be available.
- Known human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with known HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
- Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
- Women of child-bearing potential and men must agree to use adequate contraception (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 4 months after completion of pembrolizumab administration.
- Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.
Who cannot join
- Patients who have metastatic disease.
- Patients who have ongoing adverse events from prior anti-cancer therapy that would preclude completion of the proposed study treatment at the opinion of the treating investigators.
- Patients who are receiving any other investigational agents. Patients who have received other investigational agents previously who are no longer receiving these investigational agents may be eligible at the discretion of the PI.
- Prior treatment with PD-1 inhibitors in the last 6 months or progression on a PD-1 inhibitor at any time.
- Autoimmune disease or other pro-inflammatory conditions other than treated stable asthma, minor allergies (such as seasonal allergies), vitiligo or hypothyroidism.
- Active and ongoing steroid use >10 mg prednisone, except for non-systemically absorbed treatments (such as inhaled or topical steroid therapy for asthma, COPD, allergic rhinitis).
- Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous, in the opinion of the Investigator.
- Pregnant women are excluded from this study. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with breastfeeding should be discontinued if the mother is treated with pembrolizumab.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Jordan Kharofa, MD contact
United States1 site, 1 recruiting
- Recruiting
University of Cincinnati Medical Center
Cincinnati, Ohio, 45219
UCCC CTO, 513-584-7698, cancer@uchealth.com
Jordan Kharofa, MD
About this study
Official title: WOPPPR: Window of Opportunity Phase I and Phase II Trial Combining PD-1 Inhibition and Neoadjuvant Proton or Photon Radiation Therapy in Recurrent Head and Neck Squamous Cell Carcinoma
The purpose of the Phase I study is to see if it is safe to use X-ray photon radiation (XRT) and proton radiation (PT) before surgery in patients with recurrent head and neck squamous cell carcinoma (rHNSCC).
The purpose of the Phase II study is to see if using XRT or PT before immunotherapy (pembrolizumab) prior to surgery benefits patients with recurrent head and neck squamous cell carcinoma (rHNSCC).
Read the detailed description
In phase I, cohorts of 3 to 6 patients will be treated with 3 fractions of RT prior to surgery. A de-escalation cohort is planned if toxicity is exceeded in Cohort 1. The types of RT (XRT and PT) will be tested sequentially. The first cohort will include XRT followed by salvage surgery and adjuvant immunotherapy. The RP2D or dose found to be safe will be decided for XRT first. The RP2D for XRT will then be the starting dose cohort for PT to ensure the dose remains safe. The highest dose found to be safe for both types of RT will be used for Phase II. The dose escalation criteria must be met at each dose level including up to 28 days post-surgical resection in order to enroll and treat pts for phase II or de-escalate to the indicated dose level.
Phase II is a two arm window of opportunity multi-center study investigating XRT or PT with PD-1 inhibition in recurrent HNSCC. The study will be conducted in two stages with 2 independent experimental arms based on a Simons 2 Stage Design. PT followed by PD-1 inhibition (Arm 1) or XRT followed by PD-1 inhibition (Arm 2) will be independently compared to a historical control group with the primary endpoint of major pathological response (MPR) and a goal of 35% of patients achieving MPR compared to a baseline of 10% with PD-1 alone. Forty total patients with recurrent HNSCC will be screened and randomized to avoid selection bias to either PT or XRT. Based on a Simon Stage 2 Design, nine patients are required for stage I. Stage II will proceed after determination of Stage I MPR.
- Being tested
- Proton therapy, Pembrolizumab
- Medical subject headings
- Head and Neck Neoplasms, 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.
Proton therapyRadiation
Proton therapy is a type of radiation therapy that uses protons rather than x-rays. It painlessly delivers radiation to treat some types of cancer.
PembrolizumabDrug
PDL-1 immunotherapy drug
| Study group | Role | What they receive |
|---|---|---|
| Standard Radiation Therapy | Active comparator | XRT followed by PD-1 inhibition Receives: Drug: Pembrolizumab |
| Photon Therapy | Experimental | PT followed by PD-1 inhibition Receives: Radiation: Proton therapy; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicity (DLT) Evaluation defined as the number of subjects experiencing a major, non-grade 5 adverse event as defined by CTCAE v6 or a grade 5 adverse event as defined by CTCAE 6.
To determine DLTs during Phase I to determine the recommended Phase 2 dose. A DLT is defined as experiencing ≥ Gr 4 AEs prior to surgery, a delay in surgery past 5 wks from RT, or ≥ Gr 4 surgical complications or Grade 5 adverse events are defined as deaths occurring during the study period, regardless of attribution, as assessed using CTCAE v6.0 criteria.
Measured: From the initiation of study treatment to 28 days post resection.
Major Pathologic Response (MPR) defined as less than 10% viable tumor on resected tumor specimen.
To determine the major pathological response (MPR) in patients undergoing neoadjuvant X-ray photon radiation (XRT) or proton radiation (PT) with pembrolizumab followed by surgical salvage compared to a historical control group undergoing salvage surgery with PD-1 alone.
Measured: Surgery - Week 4
Secondary outcomes (2)
Disease Free Survival as measured from time of surgery until either disease recurrence or death from any cause.
To determine the disease-free survival (DFS) in patients undergoing neoadjuvant XRT or PT followed by surgical salvage compared to a historical control group undergoing salvage surgery alone. DFS is defined as the duration from time of surgery until either disease progression, recurrence or death due to any cause.
Measured: Surgery - Week 4 through 5 years
Safety using CTCAE v6.0 and toxicity evaluation.
To determine the safety of neoadjuvant pembrolizumab combined with XRT or PT prior to salvage surgery.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2025
- Study start8 Oct 2025
- Primary completionDec 2030 (estimated)
- Study completionDec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by University of CincinnatiThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jordan Kharofa, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07213934
- Sponsor's protocol ID
- UCCC-HN-24-01
- Status last verified
- Jun 2026
- First submitted
- 30 Sep 2025
- Last updated
- 1 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- WOPPPR: Window of Opportunity Phase I and Phase II Trial Combining PD-1 Inhibition and Neoadjuvant Proton or Photon Radiation Therapy in Recurrent Head and Neck Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT07213934
- Acronym / sponsor ID
- UCCC-HN-24-01
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Study start
- 8 Oct 2025 (actual)
- Primary completion
- Dec 2030 (estimated)
- Study completion
- Dec 2031 (estimated)
- First posted
- 9 Oct 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.
The purpose of the Phase I study is to see if it is safe to use X-ray photon radiation (XRT) and proton radiation (PT) before surgery in patients with recurrent head and neck squamous cell carcinoma (rHNSCC).
The purpose of the Phase II study is to see if using XRT or PT before immunotherapy (pembrolizumab) prior to surgery benefits patients with recurrent head and neck squamous cell carcinoma (rHNSCC).
Detailed description
In phase I, cohorts of 3 to 6 patients will be treated with 3 fractions of RT prior to surgery. A de-escalation cohort is planned if toxicity is exceeded in Cohort 1. The types of RT (XRT and PT) will be tested sequentially. The first cohort will include XRT followed by salvage surgery and adjuvant immunotherapy. The RP2D or dose found to be safe will be decided for XRT first. The RP2D for XRT will then be the starting dose cohort for PT to ensure the dose remains safe. The highest dose found to be safe for both types of RT will be used for Phase II. The dose escalation criteria must be met at each dose level including up to 28 days post-surgical resection in order to enroll and treat pts for phase II or de-escalate to the indicated dose level.
Phase II is a two arm window of opportunity multi-center study investigating XRT or PT with PD-1 inhibition in recurrent HNSCC. The study will be conducted in two stages with 2 independent experimental arms based on a Simons 2 Stage Design. PT followed by PD-1 inhibition (Arm 1) or XRT followed by PD-1 inhibition (Arm 2) will be independently compared to a historical control group with the primary endpoint of major pathological response (MPR) and a goal of 35% of patients achieving MPR compared to a baseline of 10% with PD-1 alone. Forty total patients with recurrent HNSCC will be screened and randomized to avoid selection bias to either PT or XRT. Based on a Simon Stage 2 Design, nine patients are required for stage I. Stage II will proceed after determination of Stage I MPR.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard Radiation Therapy | Active comparator | Drug: PembrolizumabXRT followed by PD-1 inhibition |
| Photon Therapy | Experimental | Radiation: Proton therapy, Drug: PembrolizumabPT followed by PD-1 inhibition |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Patients must have histologically or cytologically confirmed recurrent head and neck squamous cell carcinoma including oral cavity, laryngeal, hypopharyngeal, or oropharyngeal (HPV-) SCC.
- Patients must be a candidate for salvage surgical resection.
- Patients must have failed prior RT >6 months prior to recurrence with at least 30 Gy delivered to the current target volume.
- Disease must be limited to a single site or adjacent sites that can be treated in a single contiguous target volume for which the maximum total tumor dimension (GTV) must be <7 cm.
- Patients must have a CPS PD-L1 of ≥1%. This may be tested on a new biopsy or archival tissue.
Key exclusion criteria (8 listed)
- Patients who have metastatic disease.
- Patients who have ongoing adverse events from prior anti-cancer therapy that would preclude completion of the proposed study treatment at the opinion of the treating investigators.
- Patients who are receiving any other investigational agents. Patients who have received other investigational agents previously who are no longer receiving these investigational agents may be eligible at the discretion of the PI.
- Prior treatment with PD-1 inhibitors in the last 6 months or progression on a PD-1 inhibitor at any time.
- Autoimmune disease or other pro-inflammatory conditions other than treated stable asthma, minor allergies (such as seasonal allergies), vitiligo or hypothyroidism.
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 |
|---|---|---|
| Proton therapyProton therapy is a type of radiation therapy that uses protons rather than x-rays. It painlessly delivers radiation to treat some types of cancer. | Radiation | Photon Therapy |
| PembrolizumabPDL-1 immunotherapy drug | Drug | Photon Therapy, Standard Radiation Therapy |
Primary outcome
Dose Limiting Toxicity (DLT) Evaluation defined as the number of subjects experiencing a major, non-grade 5 adverse event as defined by CTCAE v6 or a grade 5 adverse event as defined by CTCAE 6.
Time frame: From the initiation of study treatment to 28 days post resection.
To determine DLTs during Phase I to determine the recommended Phase 2 dose. A DLT is defined as experiencing ≥ Gr 4 AEs prior to surgery, a delay in surgery past 5 wks from RT, or ≥ Gr 4 surgical complications or Grade 5 adverse events are defined as deaths occurring during the study period, regardless of attribution, as assessed using CTCAE v6.0 criteria.
Major Pathologic Response (MPR) defined as less than 10% viable tumor on resected tumor specimen.
Time frame: Surgery - Week 4
To determine the major pathological response (MPR) in patients undergoing neoadjuvant X-ray photon radiation (XRT) or proton radiation (PT) with pembrolizumab followed by surgical salvage compared to a historical control group undergoing salvage surgery with PD-1 alone.
2 secondary outcomes
Disease Free Survival as measured from time of surgery until either disease recurrence or death from any cause.
Time frame: Surgery - Week 4 through 5 years
Safety using CTCAE v6.0 and toxicity evaluation.
Time frame: 5 years
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 1 Jul 2026.
- Individual participant dataSharing planned: Undecided
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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.
Jordan Kharofa, MD contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Proton therapy and Pembrolizumab in people with Head and Neck Cancer and Recurrent Head and Neck Squamous Cell Carcinoma, run by University of Cincinnati 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 17 inclusion and 8 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 1 Jul 2026. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 UCCC Clinical Trials Office (513-584-7698, cancer@uchealth.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Limiting Toxicity (DLT) Evaluation defined as the number of subjects experiencing a major, non-grade 5 adverse event as defined by CTCAE v6 or a grade 5 adverse event as defined by CTCAE 6. (time frame: From the initiation of study treatment to 28 days post resection.). 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 1 Jul 2026.