Recruiting
Phase 2

Proton SFRT & Pembrolizumab

Sponsor:

Mayo Clinic

Code:

NCT07783581

Conditions

Locally Advanced Oral Cavity Squamous Cell Carcinoma

Locally Recurrent Oral Cavity Squamous Cell Carcinoma

Oral Cavity Squamous Cell Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biopsy Procedure

Biospecimen Collection

Computed Tomography

Magnetic Resonance Imaging

Pembrolizumab

Study Details

Brief summary:

This phase II trial compares the effect of adding proton spatially fractionated radiotherapy (SFRT) or photon stereotactic body radiotherapy (SBRT) to standard immunotherapy pembrolizumab before surgery (neoadjuvant) in treating patients with oral cavity squamous cell cancer that has spread to nearby tissue or lymph nodes (locally advanced) or that has come back where it first started (primary site) or near it (locoregionally recurrent) and have not had (naive) prior radiation. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. Proton SFRT is a type of external beam radiation treatment that uses streams of protons (tiny particles with a positive charge) to deliver different doses of radiation to different parts of the tumor in a grid like pattern. This type of radiation kills tumor cells but does not damage nearby tissues. SBRT is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body (except the brain). The total dose of radiation is divided into smaller doses given over several days. This type of radiation therapy helps spare normal tissue. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving neoadjuvant proton SFRT or SBRT in combination with pembrolizumab may be safe and tolerable and may be an effective approach to shrink the tumor, reduce the extent of surgery and/or the need for further treatment in patients with locally advanced or locoregionally recurrent oral cavity squamous cell cancer.

Conditions

Locally Advanced Oral Cavity Squamous Cell Carcinoma

Locally Recurrent Oral Cavity Squamous Cell Carcinoma

Oral Cavity Squamous Cell Carcinoma

Study ID

NCT07783581

Start date

Nov 4, 2026

Status verified date

Nov, 2026

Completion date

Jun 1, 2031

Anticipated

Primary completion date

Jun 1, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Patients with histologically confirmed human papillomavirus (HPV)/p16-unrelated squamous cell carcinoma of the oral cavity and:

  • Either locally advanced (T3-T4) non-metastatic disease, or
  • Radiation-naïve locoregionally recurrent disease (prior radiation to a site outside of the treatment fields is permitted)
  • Age ≥ 18 years old
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2
  • Eligible to receive immunotherapy on multidisciplinary evaluation
  • Ability to complete questionnaire(s) by themselves or with assistance
  • Provide signed written informed consent in accordance with ethical, regulatory, and institutional requirements
  • Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
  • Willing to consent to and provide tissue and blood samples for correlative research purposes (not the optional Riskguard and OncoExtra testing)
  • PD-L1 combined positive score ≥ 1

Exclusion Criteria:

  • Participation in another clinical study with an investigational product during the last 3 months (12 weeks)

  • Exception: Unless it is an observational (non-interventional) clinical study during the follow-up period of the study
  • Contraindications to pembrolizumab
  • Prior radiation therapy to the head and neck
  • Previous anticancer therapeutic received ≤ 30 days prior to registration, or adequate washout period on a per-agent basis, or concurrent anti-cancer therapeutic not specified by this protocol
  • Uncontrolled pre-existing condition(s), such as infection, congestive heart failure, hypertension, angina, arrhythmia, chronic diarrhea, psychiatric conditions, or others, that in the opinion of the treating investigator limits the ability to provide consent or longitudinal participation in this study
  • Inability to place 2 or more SFRT spheres within the tumor target
  • Prophylactic placement of feeding tubes is not allowed

Study Design

Enrollment

30 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm A (proton SFRT, pembrolizumab, surgery)

Patients receive proton SFRT QOD for up to 3 treatment fractions over 1 week. Starting within 7 days of initiating SFRT, patients receive pembrolizumab IV on day 1 of each cycle. Cycles repeat every 3 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Within 8 weeks of completing pembrolizumab, patients undergo surgical resection per standard of care. Patients also undergo blood sample collection, CT, and PET/MRI or PET/CT throughout the study. Additionally, patients may also undergo tissue biopsy at baseline and/or on study.

experimental: Arm B (photon SBRT, pembrolizumab, surgery)

Patients receive photon SBRT QOD for up to 3 treatment fractions over 1 week. Starting within 7 days of initiating SBRT, patients receive pembrolizumab IV on day 1 of each cycle. Cycles repeat every 3 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Within 8 weeks of completing pembrolizumab, patients undergo surgical resection per standard of care. Patients also undergo blood sample collection, CT, and PET/MRI or PET/CT throughout the study. Additionally, patients may also undergo tissue biopsy at baseline and/or on study.

Interventions

Biopsy Procedure

Undergo tissue biopsy

Biospecimen Collection

Undergo blood sample collection

Computed Tomography

Undergo CT or PET/CT

Magnetic Resonance Imaging

Undergo PET/MRI

Pembrolizumab

Given IV

Photon Stereotactic Body Radiation Therapy

Receive photon SBRT

Positron Emission Tomography

Undergo PET/CT or PET/MRI

Spatially-fractionated Radiation Therapy

Receive proton SFRT

Surgical Procedure

Undergo surgical resection

Primary outcome measure

  • Improvement in major pathologic response rate (MPR) [ Time Frame: At the time of surgical resection ]

Central Contacts and Locations

Central contacts

Clinical Trials Referral Office

855-776-0015mayocliniccancerstudies@mayo.edu

Locations

Mayo Clinic in Rochester

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

Clinical Trials Referral Office

855-776-0015mayocliniccancerstudies@mayo.edu

Principal Investigator:

Daniel K. Ebner, MD, MPH

More Information

Sponsor

Mayo Clinic

Last update posted

Nov 6, 2026

Last verified

Nov, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-11-07. This information was provided to ClinicalTrials.gov by Mayo Clinic on 2026-11-06. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.