The purpose of the Phase I study is to see if it is safe to use X-ray photon radiation (XRT) and proton radiation (PT) before surgery in patients with recurrent head and neck squamous cell carcinoma (rHNSCC).
The purpose of the Phase II study is to see if using XRT or PT before immunotherapy (pembrolizumab) prior to surgery benefits patients with recurrent head and neck squamous cell carcinoma (rHNSCC).
Patients must have histologically or cytologically confirmed recurrent head and neck squamous cell carcinoma including oral cavity, laryngeal, hypopharyngeal, or oropharyngeal (HPV-) SCC.
Patients must be a candidate for salvage surgical resection.
Patients must have failed prior RT >6 months prior to recurrence with at least 30 Gy delivered to the current target volume.
Disease must be limited to a single site or adjacent sites that can be treated in a single contiguous target volume for which the maximum total tumor dimension (GTV) must be <7 cm.
Patients who have metastatic disease.
Patients who have ongoing adverse events from prior anti-cancer therapy that would preclude completion of the proposed study treatment at the opinion of the treating investigators.
Patients who are receiving any other investigational agents. Patients who have received other investigational agents previously who are no longer receiving these investigational agents may be eligible at the discretion of the PI.
Prior treatment with PD-1 inhibitors in the last 6 months or progression on a PD-1 inhibitor at any time.
Parallel
Proton therapy
RadiationProton therapy is a type of radiation therapy that uses protons rather than x-rays. It painlessly delivers radiation to treat some types of cancer.
Pembrolizumab
DrugPDL-1 immunotherapy drug
Dose Limiting Toxicity (DLT) Evaluation defined as the number of subjects experiencing a major, non-grade 5 adverse event as defined by CTCAE v6 or a grade 5 adverse event as defined by CTCAE 6.
To determine DLTs during Phase I to determine the recommended Phase 2 dose. A DLT is defined as experiencing ≥ Gr 4 AEs prior to surgery, a delay in surgery past 5 wks from RT, or ≥ Gr 4 surgical complications or Grade 5 adverse events are defined as deaths occurring during the study period, regardless of attribution, as assessed using CTCAE v6.0 criteria.
Major Pathologic Response (MPR) defined as less than 10% viable tumor on resected tumor specimen.
To determine the major pathological response (MPR) in patients undergoing neoadjuvant X-ray photon radiation (XRT) or proton radiation (PT) with pembrolizumab followed by surgical salvage compared to a historical control group undergoing salvage surgery with PD-1 alone.
Disease Free Survival as measured from time of surgery until either disease recurrence or death from any cause.
To determine the disease-free survival (DFS) in patients undergoing neoadjuvant XRT or PT followed by surgical salvage compared to a historical control group undergoing salvage surgery alone. DFS is defined as the duration from time of surgery until either disease progression, recurrence or death due to any cause.
Safety using CTCAE v6.0 and toxicity evaluation.
To determine the safety of neoadjuvant pembrolizumab combined with XRT or PT prior to salvage surgery.
Percent immune cell infiltration in tumors or microenvironment in patients undergoing neoadjuvant XRT or PT followed by surgical salvage determined by IHC and/or IF and/or Flow Cytometry.
To determine immunological changes in the tumor and microenvironment in patients undergoing neoadjuvant XRT or PT followed by surgical salvage.
Overall survival (OS)
To determine the overall survival (OS) in patients undergoing neoadjuvant XRT or PT and PD-1 followed by surgical salvage compared to a historical control group undergoing salvage surgery alone.
Overall response rate measured by RECIST criteria.
To determine the overall response rate by RECIST 1.1 after RT and PD-1.
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