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:

Participants 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,
participants 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, participants 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 (expected to be treated less
than 2 years from first course of therapy and have a tracheostomy or percutaneous
endoscopic gastrostomy [PEG] tube at presentation)

- 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