This phase II trial tests effects of nivolumab in combination with chemotherapy drugs prior to radiation therapy patients with nasopharyngeal carcinoma (NPC). 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. Chemotherapy drugs, such as gemcitabine and 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 x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Researchers want to find out what effects, good and/or bad, adding nivolumab to chemotherapy has on patients with newly diagnosed NPC. In addition, they want to find out if children with NPC may be treated with less radiation therapy and whether this decreases the side effects of therapy.
Patients must be ≤ 21 years of age at the time of study enrollment
Newly diagnosed American Joint Committee on Cancer (AJCC) stage II-IV nasopharyngeal carcinoma (NPC)
Patients must have had histologic verification of the malignancy at original diagnosis
Although submission of tumor tissue for the molecular characterization initiative is not required for eligibility, it is strongly recommended
Patients who received prior radiotherapy to the head or neck
Patients who received prior chemotherapy or radiation for the treatment of any cancer in the last 3 years. These patients must also be in remission
Patients with a diagnosis of immunodeficiency
Patients with an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive agents). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Single group
Biopsy Procedure
Procedure/SurgeryUndergo tissue biopsy
Biospecimen Collection
Procedure/SurgeryUndergo blood and stool sample collection
Chest Radiography
Procedure/SurgeryUndergo chest x-ray
Cisplatin
DrugGiven IV
Computed Tomography
Procedure/SurgeryUndergo CT
Echocardiography Test
Procedure/SurgeryUndergo ECHO
Electronic Health Record Review
Other interventionAncillary studies
Fluciclovine F18
Other interventionGiven IV
Gemcitabine
DrugGiven IV
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Multigated Acquisition Scan
Procedure/SurgeryUndergo MUGA
Nivolumab
Biological/VaccineGiven IV
Positron Emission Tomography
Procedure/SurgeryUndergo PET
Quality-of-Life Assessment
Other interventionAncillary studies
Questionnaire Administration
Other interventionAncillary studies
Radiation Therapy
RadiationReceive radiation therapy
X-Ray Imaging
Procedure/SurgeryUndergo dental x-ray
Incidence of grade 3 or higher immune-related adverse events (irAE) during induction chemoimmunotherapy (CIT)
Will be assessed by Common Terminology Criteria for Adverse Events. IrAEs include diarrhea (noninfectious), colitis (noninfectious), pneumonitis (noninfectious), myocarditis, elevated alanine aminotransferase, elevated aspartate aminotransferase, pancreatitis, elevated blood bilirubin, hypophysitis and hyperthyroid considered possibly, probably, or definitely related to nivolumab.
Event-free survival (EFS)
EFS along with the 95% confidence intervals will be estimated using the Kaplan-Meier method. The EFS will be reported separately for patients with non-metastatic disease and those with metastatic disease (if there are enough patients with metastatic disease enrolled).
Objective response rate
Will be defined as the rate of responders among evaluable patients using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Feasibility success of the induction regimen
Will be defined as the completion of three cycles of induction without delay of greater than 30 days for radiation initiation due to toxicity in 80% of patients.
Cumulative incidence of local or distant relapse
Defined as a function of time since enrollment will be estimated by the method of Gray.
EFS
Will be assessed using Kaplan-Meier estimates.
Overall survival
Will be assessed using Kaplan-Meier estimates.
Proportion of patients who achieve complete response
Will be assessed by retrospective central review by the proportion of patients who achieve complete response by magnetic resonance imaging using RECIST 1.1 criteria and the proportion of patients who achieve complete metabolic response using Positron Emission Tomography Response Criteria In Solid Tumors criteria at the end of induction and the end of maintenance based on central review will be presented. A two-way table of response assessments according to the two modalities will be constructed and McNemar's test will be performed to evaluate the concordance.
Protocol deviation related to radiation therapy delivery
Will be assessed by retrospective central review. The effect of deviation, categorized as present or absent by the central reviewer, on the hazard of EFS will be estimated by Cox proportional hazard model. The hazard ratio will be reported along with 95% confidence interval.
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