Testing the Addition of an Anti-cancer Immune Therapy Drug (Nivolumab) to the Usual Chemotherapy Treatment (Cisplatin or Carboplatin With Gemcitabine) for Recurrent or Metastatic Nasopharyngeal Cancer

Exclusion Criteria

• •Diagnosed with another invasive malignancy (except non-melanomatous skin cancer) unless disease free for more than 3 years. Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) who have undergone potentially curative therapy are not excluded
• •Any prior systemic anti-cancer agents (including chemotherapy and investigational agents) for the purpose of treating locoregional and/or distant recurrence of NPC
• •Patients who have received neoadjuvant (induction) and/or adjuvant chemotherapy for primary NPC with chemotherapy (any drug regimens including those containing platinum and/or gemcitabine) at or within 6 months prior to registration are excluded (counting from the last day of the chemotherapy for the primary NPC, prior to enrolling into the current study). The following subgroups of patients are NOT excluded:
• •* Patients who have received neoadjuvant (induction) and/or adjuvant chemotherapy for primary (non-metastatic/non-recurrent) NPC more than 6 months prior to registration, counting from the last day of the chemoradiotherapy for the primary NPC, prior to enrolling into the current study
• •* For prior RT with radical intent: Patients who have prior radiotherapy (RT) to the primary and locoregional disease (i.e. non-recurrent disease) with or without concurrent cisplatin or carboplatin monotherapy are not excluded as long as they have not received any neoadjuvant/adjuvant chemotherapy within 6 months prior to registration (counting from the last day of the chemotherapy), and that the last RT fraction (with radical intent) has been given more than 3 months prior to registration
• •* For RT with palliative intent: Prior radiotherapy (RT) at or within 30 days prior to registration, this includes RT given with palliative intent (with or without concurrent cisplatin or carboplatin alone) to recurrent/ metastatic sites in patients with recurrent/metastatic NPC. The re-irradiated sites must not be the only sites of measurable recurrent disease
• •* Prior chemotherapy for cancers other than NPC is allowed as long as the last course of chemotherapy was administered more than 3 years prior to registration and the patient has remained disease-free for more than 3 years
• •Prior therapy for any indication, with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137)
• •History of severe (grade 3-4) hypersensitivity reaction to any monoclonal antibody including nivolumab and/or any of its excipients
• •Severe, active co-morbidity defined as follows:
• •* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
• •* Myocardial infarction within the last 6 months
• •* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
• •* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration
• •* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
• •* History of (non-infectious) pneumonitis that required steroids or has current pneumonitis requiring steroids and/or immunosuppressive therapy
• •* History of active TB (Bacillus tuberculosis, not known to be multi-drug resistant) as defined by the need to receive systemic treatment within the last 2 years or any known history of multi-drug resistant TB. Note: Patients who had a distant history of treated TB (not known to be multi-drug resistant) at 5 or more years from enrollment and have no current symptoms suggestive of active TB, are not excluded from this study. Note: Testing for prior exposure to TB is not required in this study since TB is endemic in parts of Asia
• •* Prior solid organ transplant or bone marrow transplant
• •* History of active primary immunodeficiency including, but not limited to acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; Note: Human immunodeficient virus (HIV) testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatment involved in this protocol may be immunosuppressive
• •* Condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone or equivalents) or other immunosuppressive medications within 14 days of registration. Inhaled or topical steroids and adrenal replacement doses \< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Steroid premedication for the prophylaxis of CT contrast-related allergies is allowed. The use of dexamethasone as an anti-emetic premedication prior to chemotherapy is also allowed
• •* Active autoimmune disease requiring systemic treatment (i.e. disease modifying agents, corticosteroids, or immunosuppressive drugs) within the past 2 years. These include but are not limited to patients with a history of immune-related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), rheumatoid arthritis, connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease
• •* Note: Patients are permitted to enroll if they have vitiligo; type I diabetes mellitus; hypothyroidism, pituitary or adrenal insufficiency requiring only hormone replacement; psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event)
• •Patients who are pregnant or breastfeeding and unwilling to discontinue breastfeeding
• •Known history of grade 3-4 allergic reaction and/or hepatic toxicity to cisplatin, carboplatin, or gemcitabine
• •* Note: For patients with known history of grade 3-4 renal toxicity to cisplatin or known history of clinically significant hearing loss (grade 2 or above) attributed to cisplatin, or other intolerances to cisplatin that are of clinical significance, carboplatin can be used in this study and therefore these patients are NOT excluded from enrollment
• •Known central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with base of skull involvement by NPC are not excluded unless their disease is directly invading the brain parenchyma and is associated with clinical symptoms (headaches, nausea and vomiting, neurological abnormalities on physical examination) and/or cerebral edema on radiological imaging
• •Patients who have received a live vaccine within 30 days prior to the first dose of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
• •History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator