A Phase II/III Randomized Study of Maintenance Nivolumab Versus Observation in Patients with Locally Advanced, Intermediate Risk HPV Positive OPCA

Study Details

Primary objective:
To assess the efficacy of concurrent definitive therapy followed by nivolumab compared with concurrent definitive therapy followed by observation in terms of progression-free survival (PFS). (Phase II) II. To assess the efficacy of concurrent definitive therapy followed by nivolumab compared with concurrent definitive therapy followed by observation in terms of overall survival (OS). (Phase III)

Secondary objectives:

1. To further assess the efficacy of nivolumab compared with observation in terms of:
   • The relationship of baseline PD-L1 expression to clinical outcome.
   • To evaluate the association of 12-week post-therapy fludeoxyglucose F-18 (FDG) positron emission tomography (PET)/computed tomography (CT) with PFS and OS.
   • To establish the prognostic value of standardized uptake value (SUV)max of primary tumor or neck nodal metastasis of baseline FDG PET/CT for OS (and/or PFS).
   • To correlate SUVmax of primary tumor or nodal metastasis of baseline FDG PET/CT with PD-L1 expression (positive vs. negative).
   • To compare the PET based therapy response assessment (Hopkins criteria) to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessment at 12 week post chemoradiation therapy, for patients who have a PET/CT scan at 12 weeks.

Inclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
2. Patients must have oropharynx cancer (AJCC 8) that is p16-positive by immunohistochemistry with smoking status: >= 10 pack-years, stage T1-2N2-N3 or T3-4N0-3 (less than 10 pack-years is considered a non-smoker) OR < 10 pack-years, stage T4N0-N3 or T1-3N2-3.
3. Patients must not have known hypersensitivity to nivolumab or compounds of similar chemical or biologic composition.
4. Patients with a history of allergic reactions attributed to platinum-based chemotherapy agents are excluded.
5. Patients must not have had prior systemic therapy, radiation treatment or surgery for p16 positive oropharyngeal squamous cell carcinoma (OPSCC).
6. Patients must not have received previous irradiation for head and neck tumor, skull base, or brain tumors.
7. Patients must not receive investigational agents within 4 weeks of enrollment or at any time while on study.
8. Patients with evidence of distant metastases or leptomeningeal disease (LMD) are excluded.
9. Patients with uncontrolled inter-current illnesses which in the opinion of the investigator will interfere with the ability to undergo therapy including chemotherapy are excluded.
10. Patients with a history of prior or second malignancy are excluded, with the exception of curatively treated non-melanoma skin cancer, or curatively treated cervical cancer; additionally, patients curatively treated for malignancy who remain disease-free at > 2 years of follow up, are not excluded.
11. Absolute neutrophil count (ANC) >= 1500/mm^3 (must be obtained =< 2 weeks prior to randomization).
12. Hemoglobin (Hgb) >= 8.0 g/dL (must be obtained =< 2 weeks prior to randomization).
13. Platelet count >= 100,000/mm^3 (must be obtained =< 2 weeks prior to randomization).
14. Creatinine clearance of >= 60 ml/min (must be obtained =< 2 weeks prior to randomization). Creatinine clearance may be measured or calculated. If calculating, creatinine clearance, use the Cockcroft-Gault formula.
15. Total bilirubin within 1.5 times the normal limits (must be obtained =< 2 weeks prior to randomization).
16. Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) within 2.0 times the normal limits (must be obtained =< 2 weeks prior to randomization).
17. Alkaline phosphatase within 1.5 times the normal limits (must be obtained =< 2 weeks prior to randomization).
18. Women must not be pregnant or breast-feeding as chemotherapy, radiation, and immunotherapy may have possible teratogenicity effects; in addition, complications from pregnancy may interfere with the ability of patients to have an uninterrupted therapy.
19. All women of childbearing potential must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy.
20. A woman of childbearing potential is any female, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months.
21. Women of childbearing potential (WOCBP) and males who are sexually active with WOCBP must use an accepted and effective method of contraception or abstain from sexual intercourse for at least one week prior to the start of treatment, and continue for 5 months after the last dose of protocol treatment for women of childbearing potential and 7 months after the last dose of protocol treatment for males who are sexually active with WOCBP.
22. Patients must have measurable disease as defined.
23. Patients must have tumor measurements with CT of neck and CT of chest within 4 weeks prior to Step 1 randomization.