Intensity-Modulated Radiation Therapy & Nivolumab for Recurrent or Second Primary Head & Neck Squamous Cell Cancer

PRIMARY OBJECTIVE:

I. To assess the 1-year progression-free survival (PFS) for patients with recurrent or second primary head and neck squamous cancer treated with intensity-modulated radiation therapy (IMRT) re-irradiation with concurrent and adjuvant nivolumab.

SECONDARY OBJECTIVES:

I. Evaluate the 1-year (yr) overall survival (OS) of patients treated with re-irradiation and nivolumab.

II. Evaluate patient quality of life (QOL).

III. Evaluate patterns of failure including local, regional and distant failure rates at 1 yr.

IV. Identify and estimate the incidence rate of acute and late toxicities associated with combined re-irradiation and concurrent and adjuvant nivolumab.

TERTIARY OBJECTIVE:

I. To identify potential biomarkers related to clinical benefit to concurrent and adjuvant nivolumab and re-irradiation in patients with recurrent or second primary (RSP) head and neck squamous cell carcinoma (HNSCC).

OUTLINE:

Patients receive nivolumab intravenously (IV) over 30 minutes on weeks -2, 0, 2, 4, and 6 and undergo IMRT once daily beginning on week 0 for up to 6-6.5 weeks. Beginning week 10, patients receive nivolumab IV over 30 minutes every 4 weeks for up to 10 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 2 years from the beginning of radiation therapy.

Inclusion criteria

• Patients with recurrent squamous cell carcinoma or a second primary arising in a previously irradiated field
• Life expectancy of greater than 6 months
• Patients cannot have distant metastases and have to be candidates for curative re-irradiation
• Patients with salivary gland tumors are excluded (patients with nasopharynx or sinonasal cancers can participate)
• Patients with unresectable disease are eligible
• Patients who undergo surgical resection will be allowed regardless of human papilloma virus (HPV) status provided they have one of the following criteria:

• Positive margins on pathology
• Evidence of extracapsular spread on nodal pathology
• Gross residual disease on postoperative or simulation imaging
• N2/3 disease
• T3/4 disease
• Multifocal perineural invasion and/or lymphovascular space invasion
• The majority of the anticipated target volume (> 50%) must have been previously treated to ≥ 40 Gy; prior radiation therapy (RT) must have been completed > 6 months prior to initiation of IMRT reirradiation; if previous RT records are unavailable, investigators can estimate the dose to previously treated tissues based on completion notes or other treatment history
• An Eastern Cooperative Oncology Group (ECOG) performance score 0-2
• Granulocytes > 1500/mm³
• Platelets > 100,000/mm³
• Bilirubin < 1.5 mg/dl
• Creatinine < 1.5 mg/dl
• No other concurrent invasive malignancies treated for the past year (localized prostate cancer or early stage skin cancer are not exclusion criteria)
• Patients with carotid artery involvement or encasement will be allowed provided they have no symptoms related to carotid involvement
• No prior exposure to immunotherapy agents
• Ability to understand and the willingness to sign a written informed consent document

Exclusion criteria

• Any known factors that would pose a contraindication to receiving nivolumab
• Recursive partitioning analysis (RPA) class III patients defined as those expected to begin reirradiation within 2 years of first course of radiation therapy AND are percutaneous endoscopic gastrostomy (PEG) dependent or have a tracheostomy (patients who have undergone total laryngectomy are not excluded)
• Patients with metastases
• Prior treatment with a programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor
• Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to enrollment
• Patients with primary salivary gland cancers are excluded
• Patients who have had chemotherapy or biological therapy within 4 weeks of registration
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, autoimmune disease requiring systemic steroids, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients who are pregnant or breast-feeding
• Patients with known active human immunodeficiency virus (HIV), hepatitis (hep) B, or hep C infection
• Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease