Chemotherapy and Locoregional Therapy Trial (Surgery or Radiation) for Patients With Head and Neck Cancer

Inclusion Criteria

• Patients must have pathologically confirmed HPV-positive head and neck squamous cell carcinoma of the oropharynx. Confirmed HPV-positive disease of other subsites are uncommon but also eligible.
• HPV testing must be compliant with the following criteria:
• p16 IHC positivity is sufficient to enroll and initiate treatment (p16 IHC interpretation to follow guidelines by Jordan and Lingen et al89).
• p16 IHC positivity is to be validated using an HPV PCR during the induction phase. This is essential as HPV genotype influences treatment arm allocation, with non-HPV16 HPV strains being considered high risk.
• Availability of ≥10 unstained 5 micron slides (to be provided to HTRC at the University of Chicago). Patients who cannot fulfill this requirement will need to undergo a new biopsy prior to enrollment on study.
• Patients must be at least 18 years of age.
• Patients with AJCC (7th edition, 2010) N2-N3 nodal disease or T3-T4 primary tumor.
• Measurable disease (either primary site and/or nodal disease) by RECIST 1.1 criteria.
• No previous radiation or chemotherapy for a head and neck cancer.
• No complete surgical resection for a head and neck cancer within 8 weeks of enrollment (although lymph node biopsy including excision of an individual node with presence of residual nodal disease, or surgical biopsy/excision of the tumor with residual disease is acceptable).
• ECOG performance status 0-1 (Karnofsky greater than or equal to 80%).
• Normal Organ Function
• Leukocytes ≥3000/mm3,
• platelets ≥100,000/mm3,
• absolute neutrophil count ≥1,500,
• hemoglobin >9.0 gm/dL,
• AST and ALT 2.9 gm/dL, 29 Version Date: 12/28/2016
• total bilirubin ≤1.5 mg/dl,
• creatinine clearance >45 mL/min (or SCr 18.
• Women of childbearing potential (WOCBP=premenopausal woman capable of becoming pregnant) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug.
• Women must not be breastfeeding.
• WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 5 half-lives of study drug(s) plus 30 days (duration of ovulatory cycle) for a total of 23 weeks post-treatment completion.
• Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 5 half-lives of study drug(s) plus 90 days (duration of sperm turnover) for a total of 31 weeks post treatment completion.
• Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, they must still undergo pregnancy testing as described in this section.
• Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the use of highly effective methods of contraception. Highly effective methods of contraception have a failure rate of grade 1
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy in excess of physiologic dose or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active tuberculosis (Bacillus Tuberculosis infection)
• Has hypersensitivity to nivolumab or any other drug used in this protocol.
• Has had a prior systemic anti-cancer treatment within the last 8 weeks
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer or any tumors that are not likely to influence live expectancy in the subsequent 3 years without active treatment (e.g. low grade prostate