A Study Using Nivolumab, in Combination With Chemotherapy Drugs to Treat Nasopharyngeal Carcinoma (NPC)

PRIMARY OBJECTIVE: I. To evaluate safety of combining chemotherapy (cisplatin and gemcitabine) with an anti-PD1 immune checkpoint inhibitor (nivolumab) in children, adolescents and young adults with nasopharyngeal carcinoma (NPC) by determining the rate of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher immune related adverse events (irAEs). SECONDARY OBJECTIVES: I. To estimate the 2-year event-free survival (EFS) of children, adolescents and young adults with NPC who are treated with induction chemoimmunotherapy (CIT), followed by consolidation chemoradioimmunotherapy (CRIT, cisplatin, nivolumab and response-adjusted, dose de-escalated radiation therapy), and nivolumab maintenance therapy. II. To evaluate the objective response rate (ORR) including complete responders and partial responders (complete response \[CR\] + partial response \[PR\]) of neoadjuvant CIT. III. To evaluate feasibility of combining chemotherapy (cisplatin and gemcitabine) with an anti-PD1 immune checkpoint inhibitor (nivolumab) in children, adolescents and young adults with nasopharyngeal carcinoma (NPC). IV. To evaluate the cumulative incidence of local and distant relapse. EXPLORATORY OBJECTIVES: I. To estimate 5-year EFS and overall survival (OS) of children with NPC who are treated with induction CIT followed by consolidation CRIT, and nivolumab maintenance therapy. II. To compare response assessed by fludeoxyglucose F18 (FDG) positron emission tomography (PET) versus magnetic resonance imaging (MRI). III. To determine treatment outcomes for patients treated with radiation per protocol versus (vs) deviation. IV. To evaluate outcomes comparing patients receiving intensity modulated radiation therapy (IMRT) to proton therapy. V. To objectively measure both acute and long-term toxicity including immune related adverse events and radiation late effects. VI. To evaluate swallowing dysfunction using patient reported outcome (PRO) measures for children and adults throughout the protocol for up to 5 years. VII. To evaluate quality of life (QOL) using Patient-Reported Outcomes Measurement Information System (PROMIS) multidimensional questionnaire throughout the protocol for up to 5 years. VIII. To correlate the lymphocyte to monocyte ratio on complete blood counts (CBCs) with treatment response and outcomes. IX. To collect and bank specimens (including tumor, blood and stool) for future research studies. OUTLINE: INDUCTION THERAPY: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 of each cycle, gemcitabine IV over 30 minutes on days 1 and 8 of each cycle, and cisplatin IV over 3-6 hours on day 1 of each cycle. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION THERAPY: Patients receive nivolumab IV over 30 minutes on day 1 of each cycle and cisplatin IV over 3-6 hours on day 1 of cycles 1-2. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive concurrent radiation therapy on trial. MAINTENANCE THERAPY: Patients receive nivolumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening and as clinically indicated on trial. Patients undergo MRI, FDG PET, and computed tomography (CT) throughout the trial and chest x-ray during follow-up. Patients also undergo dental x-ray imaging on the trial. Patients may optionally undergo tissue biopsy, blood and stool sample collection during screening and on trial. After completion of study treatment, patients are followed up every 3 months for 12 months, every 6 months until 24 months off therapy, and then yearly until 5 years off therapy.