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

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

Interventions

PROCEDURE

Biopsy Procedure

Undergo tissue biopsy

PROCEDURE

Biospecimen Collection

Undergo blood sample collection

PROCEDURE

Computed Tomography

Undergo CT or PET/CT

PROCEDURE

Magnetic Resonance Imaging

Undergo PET/MRI

BIOLOGICAL

Pembrolizumab

Given IV

RADIATION

Photon Stereotactic Body Radiation Therapy

Receive photon SBRT

PROCEDURE

Positron Emission Tomography

Undergo PET/CT or PET/MRI

RADIATION

Spatially-fractionated Radiation Therapy

Receive proton SFRT

PROCEDURE

Surgical Procedure

Undergo surgical resection

Sponsors & Collaborators

• Mayo Clinic

  lead OTHER

Principal Investigators

• Daniel K. Ebner, MD, MPH · Mayo Clinic in Rochester

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-09-07

Primary Completion

2030-04-01

Completion

2030-04-01

FDA Drug

Yes

Countries

• United States

Study Locations