A Phase II / III Randomized Study of Maintenance Nivolumab versus Observation in Patients with Locally Advanced, Intermediate Risk HPV Positive OPCA
18 Years and older, Male and Female
This phase II / III trial studies how well chemotherapy and radiation therapy with nivolumab or observation work in treating patients with intermediate risk HPV-positive oropharyngeal cancer that has spread to nearby tissue or lymph nodes. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether chemotherapy and radiation therapy with nivolumab or observation works better in treating patients with HPV-positive oropharyngeal cancer.
I. 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)
I. The relationship of baseline PD-L1 expression to clinical outcome.
II. To evaluate the predictive value of human papillomavirus (HPV)16 E6 and E7 deoxyribonucleic acid (DNA) in saliva and plasma, at baseline, 12 weeks and 9 months after completion of radiation on PFS and OS in both arms of the study.
III. To evaluate the tumor mutation burden by whole exome sequencing of the initial pretreatment tissue sample as well as samples obtained at the time of progression.
IV. To evaluate the association of 12 week post therapy fludeoxyglucose F-18 (FDG) positron emission tomography(PET)/computed tomography (CT) with PFS and OS.
V. 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).
VI. To correlate SUVmax of primary tumor or nodal metastasis of baseline FDG PET/CT with PD-L1 expression (positive vs. negative).
VII. To correlate the post therapy (cisplatin + radiation therapy [RT]) FDG PET/CT with saliva or plasma levels of HPV DNA collected at the time of the standard 3 months PET/CT scan as well as 6 months later (i.e. 9 months post therapy) for both the observation and Nivolumab groups.
VIII. 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.
OUTLINE: Patients are randomized to Arm A or Arm B. Patients in Arm B may cross-over to Arm C with clearly documented disease progression.
ARM A: Patients receive cisplatin intravenously (IV) over 60 minutes weekly and intensity modulated radiation therapy (IMRT) 5 days a week for 7 weeks for a total of 35 fractions. Within 4 weeks after completion of concurrent therapy, patients receive nivolumab IV once weekly over 30 minutes every 4 weeks for 12 months in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive cisplatin IV over 60 minutes weekly and IMRT 5 days a week for 7 weeks for a total of 35 fractions, and then go on observation. Patients will be offered the option to cross-over to Arm C if they have clearly documented progression within 12 months from the end of cisplatin/radiation therapy.
ARM C: Patients receive nivolumab IV over 30 minutes every 4 weeks for 12 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3-6 months for 3 years and then annually for a total of 10 years.
Treatment Sites in Georgia
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