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NCT Number: NCT07783581

Proton Spatially Fractionated Radiotherapy or Photon Stereotactic Body Radiotherapy in Combination With Pembrolizumab Before Surgery for the Treatment of Locally Advanced and Radiation-Naive Locoregionally Recurrent Oral Cavity Cancer, OSPRI Trial

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.

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Key information

Conditions

Locally Advanced Oral Cavity Squamous Cell Carcinoma Carcinoma Carcinoma, Squamous Cell Head and Neck Neoplasms Locally Recurrent Oral Cavity Squamous Cell Carcinoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Oral Cavity Squamous Cell Carcinoma Squamous Cell Carcinoma of Head and Neck

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location contact

Clinical Trials Referral Office

CONTACT

[email protected]

855-776-0015

Daniel K. Ebner, MD, MPH

PRINCIPAL_INVESTIGATOR

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Biopsy Procedure

Procedure

Undergo tissue biopsy

Other names: Biopsy, BIOPSY_TYPE, Bx

Biospecimen Collection

Procedure

Undergo blood sample collection

Other names: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Computed Tomography

Procedure

Undergo CT or PET/CT

Other names: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Magnetic Resonance Imaging

Procedure

Undergo PET/MRI

Other names: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Pembrolizumab

Biological

Given IV

Other names: BCD-201, GME 751, GME751, Keytruda, Lambrolizumab, MK 3475, MK-3475, MK3475, Pembrolizumab Biosimilar BCD-201, Pembrolizumab Biosimilar GME751, Pembrolizumab Biosimilar QL2107, Pembrolizumab Biosimilar RPH-075, Pembrolizumab Biosimilar SB27, QL2107, RPH 075, RPH-075, RPH075, SB 27, SB-27, SB27, SCH 900475, SCH-900475, SCH900475

Photon Stereotactic Body Radiation Therapy

Radiation

Receive photon SBRT

Other names: Photon SBRT

Positron Emission Tomography

Procedure

Undergo PET/CT or PET/MRI

Other names: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Spatially-fractionated Radiation Therapy

Radiation

Receive proton SFRT

Other names: GRID Therapy, SFRT, Spatially Fractionated Radiation Therapy

Surgical Procedure

Procedure

Undergo surgical resection

Other names: Operation, Surgery, Surgery Type, Surgery, NOS, Surgical, Surgical Intervention, Surgical Interventions, Surgical Procedures, Type of Surgery

Primary outcomes

  1. Improvement in major pathologic response rate (MPR)

    Time frame: At the time of surgical resection

    MPR is defined from pathologic evaluation of the surgically resected tumor, demonstrating less than 10% of residual tumor in the resection sample (≥90% disease reduction). Will be assessed using a Bayesian pick-the-winner randomized phase-II clinical trial design.

Secondary outcomes

  1. Pathologic complete response rate

    Time frame: At the time of surgical resection

    Pathologic complete response rate is defined from pathologic evaluation of the surgically resected tumor, demonstrating no signs of residual disease following immuno-radiation. This will be calculated separately for Arm A and for Arm B.

  2. Percent of patients receiving the prescribed therapy

    Time frame: Up to 1 year

    Will be defined as the number of patients who received the prescribed therapy divided by the number of evaluable patients who signed a consent form and began treatment. This will be calculated separately for Arm A and Arm B.

  3. Incidence of Adverse Events (AEs) Prior to Surgery:

    Time frame: From the time of registration until surgery

    Overall AEs, overall toxicities, and by maximum grade per type of AE per patient of the AEs that occur before surgery will be explored and summarized descriptively, mainly through the use of frequency tables. Toxicity is defined as an adverse event that is classified as possibly, probably, or definitely related to study treatment. AEs are graded per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 6.0.

Study contacts

Contact information is provided by the study sponsor or research team.

Clinical Trials Referral Office

CONTACT

[email protected]

855-776-0015

Sponsors and collaborators

Lead sponsor

Mayo Clinic

Other

Registry information

Official study title

Phase II: Randomized Neoadjuvant Treatment of Oral Cavity Cancer With Spatially Fractionated Proton Radiotherapy and Immunotherapy (OSPRI)

Important dates

Study start
2026
Primary completion
2030
Study completion
2030
First posted
Aug 25, 2026
Registry last updated
Aug 25, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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