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

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

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.

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