Locally Advanced Oral Cavity Squamous Cell Carcinoma, Locally Recurrent Oral Cavity Squamous Cell Carcinoma, Oral Cavity Squamous Cell Carcinoma
Conditions
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.
Interventions
PROCEDUREBiopsy Procedure
Undergo tissue biopsy
PROCEDUREBiospecimen Collection
Undergo blood sample collection
PROCEDUREComputed Tomography
Undergo CT or PET/CT
PROCEDUREMagnetic Resonance Imaging
Undergo PET/MRI
BIOLOGICALPembrolizumab
Given IV
RADIATIONPhoton Stereotactic Body Radiation Therapy
Receive photon SBRT
PROCEDUREPositron Emission Tomography
Undergo PET/CT or PET/MRI
Receive proton SFRT
PROCEDURESurgical Procedure
Undergo surgical resection
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in major pathologic response rate (MPR) | 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
| Measure | Time frame | Description |
|---|---|---|
| Pathologic complete response rate | 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. |
| Percent of patients receiving the prescribed therapy | 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. |
| Incidence of Adverse Events (AEs) Prior to Surgery: | 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. |
Countries
United States
Contacts
CONTACTClinical Trials Referral Office
PRINCIPAL_INVESTIGATORDaniel K. Ebner, MD, MPH
Mayo Clinic in Rochester
Outcome results
None listed