Pembrolizumab and Radiation Therapy in Treating Patients with Head and Neck Squamous Cell Carcinoma

Inclusion Criteria

• Pathologically confirmed squamous cell carcinoma of the head and neck with evidence of metastatic disease or locally recurrent disease; patients without pathologic or cytologic evidence of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation
• Patients must have evidence of radiologic or clinical disease progression during or within 6 months of previous treatment with systemic PD-1 directed therapy, or have stable disease on prior PD-1 therapy (at least 6 doses) and/or have been deemed not to derive clinical benefit from PD-1 directed treatment; PD-1 directed treatment includes treatment with antibodies targeting the PD-1 receptor such as pembrolizumab or nivolumab, as well as PD-L1 targeted antibodies such as durvalumab; these agents may have been administered as part of a clinical trial, and/or in combination with other immunologic agents such as CTLA-4 inhibitors or other investigational or standard of care agents/treatments
• Patients must have least 1 non-central nervous system (CNS) based lesion; palliative radiation must be potentially indicated for at least one lesion, and this lesion must be a reasonable candidate for radiation to a dose of 8 Gy in 3-5 fractions as deemed by a treating radiation oncologist in terms of the ability to meet standardly accepted radiation dose constraints; any unirradiated lesions must not require urgent palliative local treatment
• Prior systemic therapy: patients must be at least 2 weeks from prior chemotherapy, biological agents, immunotherapy or any investigational drug product, with adequate recovery of toxicity
• Prior radiation therapy: patients must be at least 2 weeks from prior radiation therapy
• Concurrent administration of other cancer specific therapy during the course of this study is not allowed
• There is no upper age limit but the patients must be able to medically tolerate the regimen; adverse event data are currently unavailable on the use immune checkpoint blockade for participants < 18 years of age, and thus children are excluded from this study
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1
• Ability to understand and the willingness to sign a written informed consent document
• Female subjects of childbearing potential must have a negative serum pregnancy test at screening
• Female and male subjects of childbearing potential must agree to use an adequate method of contraception; contraception is required prior to study entry and for the duration of study participation and 4 months after completion of pembrolizumab administration; Note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
• Leukocytes >= 3,000/mcl
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Hemoglobin >= 9 g/dl
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) =< 2.5 x institutional ULN
• AST(SGOT)/ALT(SGPT) for patients with documented liver metastases, =< 5 x institutional ULN
• Creatinine =< 1.5 x within normal institutional ULN OR
• Creatinine clearance >= 60 mL/min/1.73 m^2 for participants with creatinine levels above institutional ULN
• International normalized ratio (INR) or prothrombin time (PT) < 1.5 times the upper limit of normal unless subject is receiving anticoagulant therapy, as long as PT or partial prothrombin time (PTT) is within therapeutic range of intended use of anticoagulants
• Activated partial thromboplastin Time (aPTT) < 1.5 times the upper limit of normal unless subject is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Laboratory tests required for eligibility must be completed within 14 days prior study entry; baseline tumor measurements must be documented from tests within 28 days of study entry; other non-laboratory tests must be performed within 28 days of study entry

Exclusion Criteria

• Metastatic disease impinging on the spinal cord or threatening spinal cord compression
• Surgical fixation of bone lesion to be irradiated is required and indicated to provide mechanical stability
• Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms; participants with previously diagnosed brain metastases are eligible if they have completed treatment at least 2 weeks prior to trial therapy initiation, are neurologically stable, and have recovered from the acute effects of radiotherapy or surgery; any corticosteroid use for brain metastases must have been discontinued without the subsequent appearance of symptoms for >= 2 weeks before the initiating protocol therapy; treatment for brain metastases may include surgery, whole brain radiotherapy, radiosurgery, or a combination as deemed appropriate by the treating physician
• Participants who are receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab or previous toxicity attributed to pembrolizumab or other PD-1 directed therapy that led to permanent drug discontinuation
• Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Clinically significant electrocardiogram (ECG) abnormality, including a marked baseline prolonged QT/QTc ([QT interval/corrected QT interval], e.g., a repeated demonstration of a QTc interval > 500 ms)
• Pregnant women are excluded from this study because immunotherapy has the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with immunotherapy, breastfeeding should be discontinued if the mother is treated on this protocol
• Individuals with a history of a different malignancy are ineligible except for the following circumstances: if they have been disease-free for at least 2 years and are deemed by the investigator to be at low risk for recurrence of that malignancy; or if diagnosed and treated for cervical cancer in situ, low risk prostate cancer (treated or prostate specific antigen [PSA] being monitored without treatment) or basal cell or squamous cell carcinoma of the skin
• Human immunodeficiency virus (HIV)-positive individuals on combination anti-retroviral therapy are ineligible because of the potential for interaction between immunotherapy and these medications
• Has history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, non-infectious pneumonitis
• Active, suspected or prior documented autoimmune disease that has required systemic treatment in the last 2 years with immune modifying agents (e.g. replacement therapy such as thyroxine, insulin or physiologic corticosteroids is not an exclusion criteria)
• The subject is known to be positive for hepatitis B surface antigen (HepBsAg), or hepatitis C virus (HCV) ribonucleic acid (RNA)
• Lack of availability for follow up assessments
• The investigator’s belief that the subject is medically unfit to receive pembrolizumab and or unsuitable for any other reason
• Has received a live vaccine within 30 days of planned start of study therapy