Preoperative Immune Checkpoint Inhibitor for Patients With Primary Untreated or Recurrent/Metastatic SCCHN
Preoperative Immune Checkpoint Inhibitor for Patients With Primary Untreated or Recurrent/Metastatic SCCHN
Nivolumab (also known as BMS-936558) before surgery to people with newly diagnosed or
 recurrent squamous cell carcinoma of head and neck (SCCHN).
This research is being done to see if it is safe and feasible to give the investigational
 drugs, nivolumab (also known as BMS-936558) before surgery to people with newly diagnosed or
 recurrent squamous cell carcinoma of head and neck (SCCHN). Patients with recurrent disease
 may have a limited number of sites of metastatic (spread) squamous cell carcinoma of head and
 neck. Another goal of this study is to learn how nivolumab impacts the immune system's
 ability to treat the cancer. While nivolumab is approved by the U. S. Food and Drug
 Administration (FDA) for the treatment of patients with metastatic SCCHN with progression on
 or after platinum-based chemotherapy, the word "investigational" in this context means that
 the study drugs are not approved by the FDA for the treatment of head and neck cancers prior
 to surgery and thus is still being tested in research studies. However, the FDA is allowing
 the use of nivolumab in this study.

 This study will have two arms. Cohort (arm) 1 will examine one dose of nivolumab given about
 4 weeks before surgical resection (removal) of a newly diagnosed SCCHN. Twelve patients will
 be enrolled to this arm. Cohort 2 will examine one dose of nivolumab given about 4 weeks
 before surgical resection (removal) of SCCHN which has recurred and possibly spread to
 distant sites, but still can be resected with one surgery. Twelve patients will be enrolled
 to this arm.
Inclusion:

 Cohort 1: Subjects must have histologically confirmed previously untreated squamous cell
 carcinoma of the head and neck which is amenable to surgical resection as part of standard
 of care.

 Cohort 2: Subjects must have histologically confirmed recurrent squamous cell carcinoma of
 head and neck, which is amenable for salvage surgery. Sites of recurrence may either be
 locoregional or distant if resection can be done ideally in one surgical field.

 -  The primary site should be a head and neck squamous cell carcinoma (including, but not
 limited to oral cavity, oropharynx, hypopharynx, or larynx, paranasal sinuses, nasal
 cavity). Squamous cell carcinoma of unknown primary, diagnosed in lymph nodes in neck,
 can be included but should be tested for p16 and confirmed specific assay.

 -  Subjects with oropharyngeal primary tumors must have confirmation of HPV tumor status
 per clinical standards, although not necessary at enrollment.

 -  Subjects must have been determined to be candidates for surgical resection by a
 multidisciplinary team including a surgeon, a medical oncologist and a radiation
 oncologist.

 -  Subjects must have at least one lesion that can be biopsied at baseline.

 -  Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.

 -  Age >18 years.

 -  Life expectancy of greater than 6 months.

 -  Patients must have normal organ and marrow function as defined below:

 -  leukocytes ≥ 1,500/mcL

 -  absolute neutrophil count ≥ 1,000/mcL

 -  platelets ≥ 100,000/mcL

 -  total bilirubin ≤ 1.5 X institutional upper limit of normal (except subjects with
 Gilbert syndrome, who can have total bilirubin < 3.0 mg/dL)

 -  AST(SGOT)/ALT(SGPT) ≤ 3 X institutional upper limit of normal

 -  Creatinine OR creatinine clearance within normal institutional limits OR ≥ 40
 mL/min (using modified Cockcroft-Gault formula) for patients with creatinine
 levels above institutional normal.

 -  Resting and walking O2 saturation must remain above 90% at the time of screening

 -  Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy
 test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to
 the start of study treatment.

 -  Women must not be breastfeeding

 -  Women of childbearing potential (WOCBP) must agree to follow instructions for
 method(s) of contraception for the duration of treatment with study treatment and for
 5 months post-treatment completion. Women should use an adequate method(s) of
 contraception (Refer to nivolumab IB for WOCBP and methods of contraception to be
 provided)

 -  Males who are sexually active with WOCBP must agree to follow instructions for
 method(s) of contraception (Refer to protocol appendix E) for the duration of
 treatment with study treatment(s) and 7 months post-treatment completion. In addition,
 male participants must be willing to refrain from sperm donation during this time. Men
 who are sexually active with WOCBP must agree to follow instructions for method(s) of
 contraception

 -  Patient understands the study regimen, its requirements, risks and discomforts and is
 able and willing to sign the informed consent form. Voluntary signed and dated IRB/IEC
 approved written informed consent form in accordance with regulatory and institutional
 guidelines must be obtained before the performance of any protocol related procedures
 that are not part of normal patient care. Subjects must be competent to report AEs,
 understand the drug dosing schedule and use of medications to control AEs.

 -  Measurable disease - either radiologically (per RECIST) or clinically measurable on
 exam in order to assess treatment response.

 Exclusion Criteria

 -  Any active history of a known autoimmune disease. Subjects with vitiligo, type 1
 diabetes mellitus, residual hypothyroidism requiring hormone replacement, or
 conditions not expected to recur in the absence of an external trigger are permitted
 to enroll.

 -  Patients who have had prior chemotherapy for newly diagnosed (cohort 1) or recurrent
 (cohort 2) head and neck cancer. In cohort 2 only, previous perioperative chemotherapy
 or chemoradiation for the management of localized or locally advanced disease
 permitted.

 -  Patients who had prior surgical resection of distant metastasis (metastatectomy)
 within 3 months of enrollment.

 -  Patients who received prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti
 CD137, anti-CTLA-4 antibody therapies, any other antibody or drug specifically
 targeting T-cell co-stimulation or checkpoint pathways. Any live / attenuated vaccine
 (eg varicella, zoster, yellow fever, rotavirus, oral polio and measles, mumps, rubella
 (MMR)) during treatment and until 100 days post last dose.

 -  Patients with uncontrolled brain metastases

 -  Patients with brain metastases must have stable neurologic status following local
 therapy (surgery or radiation) for at least 2 weeks without the use of steroids or on
 stable or decreasing dose of < 10mg daily prednisone (or equivalent), and must be
 without neurologic dysfunction that would confound the evaluation of neurologic and
 other adverse events. Patients with a history of carcinomatous meningitis are not
 eligible.

 -  Patients who have an active concurrent malignancy that is not controlled/cured and
 could impact life expectancy within the next 3 years. E.g. patients with localized
 cutaneous squamous cell carcinoma or basal cell carcinoma or treated prostate cancer
 with no evidence of disease progression may be allowed to enroll after review by the
 study team.

 -  Uncontrolled inter-current illness including, but not limited to, ongoing or active
 infection, administration of live vaccination in the prior 3 months, symptomatic
 congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia,
 myocardial infarction or new onset angina within six months of enrollment, or
 psychiatric illness/social situations that would limit compliance with study
 requirements.

 -  Women who are pregnant or nursing.

 -  Men with female partners who are not willing to use contraception.

 -  Active infection with hepatitis B or hepatitis C.

 -  Patients with a condition requiring systemic treatment with either corticosteroids
 (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14
 days of randomization. Inhaled or topical steroids and adrenal replacement steroid
 doses < 10 mg daily prednisone equivalent, are permitted in the absence of active
 autoimmune disease.

 -  Patients EBV+ with nasopharynx carcinoma

 -  Patient with HIV are excluded given the unknown risk of interaction with HAART and the
 unknown benefit of immunotherapy in this population.

 -  Participants who have received a live / attenuated vaccine within 30 days of first
 treatment.