Nivolumab in Treating Patients With Recurrent and/or Metastatic Nasopharyngeal Cancer
Condition: Nasopharyngeal Nonkeratinizing Carcinoma; Recurrent Nasopharynx Carcinoma; Stage III Nasopharyngeal Carcinoma AJCC v7; Stage IV Nasopharyngeal Carcinoma AJCC v7; Stage IVA Nasopharyngeal Carcinoma AJCC v7; Stage IVB Nasopharyngeal Carcinoma AJCC v7; Stage IVC Nasopharyngeal Carcinoma AJCC v7
MeSH terms: Carcinoma; Nasopharyngeal Carcinoma; Recurrence
Intervention: Laboratory Biomarker Analysis; Nivolumab
Intervention description: Correlative studies; Given IV
Intervention MeSH terms: Nivolumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well nivolumab works in treating patients with nasopharyngeal
      cancer that has returned after a period of improvement (recurrent) and/or has spread to other
      parts of the body (metastatic). Monoclonal antibodies, such as nivolumab, may block tumor
      growth in different ways by targeting certain cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Histologically or cytologically confirmed non-keratinizing nasopharyngeal carcinoma
             (NPC) that has recurred at locoregional and/or distant sites; NOTE: patients with
             local recurrence at the bony skull-base as the only site of index disease are
             excluded; patients with locoregional recurrence without distant metastases must have
             undergone radical radiotherapy previously

          -  Measurable disease according to the RECIST criteria (version 1.1), for the evaluation
             of measurable disease

          -  Received one or more lines of chemotherapy, which must include prior treatment with a
             platinum agent and must not be amenable to potentially curative radiotherapy or
             surgery

          -  Archived or fresh tumor sample available; willingness to donate blood and tissue for
             mandatory correlative research studies

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

          -  Absolute neutrophil count >= 1.5 x 10^9/L

          -  Platelet count >= 100 x 10^9/L

          -  Hemoglobin >= 8.0 g/dL

          -  Serum alanine aminotransferase ([ALT]; serum glutamate-pyruvate transferase [SGPT]),
             or serum aspartate aminotransferase [AST] where available at the center) < 2.5 x upper
             limit of normal (ULN), OR < 5 x ULN in the presence of liver metastases

          -  Serum total bilirubin < 2 x ULN (except patients with Gilbert syndrome, who can have
             total bilirubin < 3.0 mg/dL)

          -  Serum creatinine < 1.5 x ULN

        Exclusion Criteria:

          -  Any of the following:

               -  Chemotherapy =< 4 weeks prior to registration

               -  Radiotherapy =< 4 weeks prior to registration

               -  Nitrosoureas =< 6 weeks prior to registration or

               -  Mitomycin C =< 6 weeks prior to registration

               -  Those who have not recovered from adverse events (to grade =< 1 in severity) due
                  to agents administered more than 4 weeks earlier; prior palliative radiotherapy
                  to bone metastases =< 2 weeks prior to registration (i.e. prior palliative
                  radiotherapy to bone metastases is allowed if it is performed > 2 weeks prior to
                  registration)

          -  Prior investigational agents =< 4 weeks prior to registration

          -  Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-cytotoxic T-lymphocyte
             antigen 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting
             T-cell co-stimulation or immune checkpoint pathways

          -  Known brain metastases or leptomeningeal metastases; NOTE: symptomatic, and/or if they
             require immunosuppressive doses of corticosteroids (e.g. > 10 mg/day prednisone or
             equivalents) for at least 2 weeks prior to study drug administration; patients with
             treated brain metastases who are deemed clinically stable and without radiological
             progression on positron emission tomography (PET), MRI or computed tomography (CT)
             scan performed =< 8 weeks of study entry, are not excluded; NOTE: primary
             nasopharyngeal cancers that directly invade the skull base and extend into the
             infratemporal fossa (e) are not regarded as brain metastases and are not excluded

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to nivolumab

          -  History of severe hypersensitivity reaction to any monoclonal antibody

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Any of the following:

               -  Pregnant women

               -  Nursing women

               -  Men or women of childbearing potential who are unwilling to employ adequate
                  contraception NOTE: breastfeeding should be discontinued if the mother is treated
                  with nivolumab; women of childbearing potential and men must use two forms of
                  contraception (hormonal or barrier method of birth control; abstinence) prior to
                  study entry and for the duration of study participation; they must adhere to
                  contraception for a period of 31 weeks after the last dose of nivolumab

          -  For patients with unknown human immunodeficiency virus (HIV) status at the time of
             enrollment, HIV serology must be tested during screening; patients who are tested
             positive for HIV could be included if there is an adequate cluster of differentiation
             4 (CD4) count (> 350/ul) on a stable regimen of highly active anti-retroviral therapy
             (HAART) with no detectable or minimal viral burden, and no active infections

          -  For patients with unknown hepatitis B virus surface antigen (HbsAg) status, must be
             tested during study screening; patients who are tested positive test for HBsAg are
             excluded if they have inadequately controlled hepatitis B and/or Child-Pugh Class B or
             C cirrhosis; however, patients with adequately controlled hepatitis are not excluded
             from the study if they satisfy all of the following criteria: (i) must be receiving a
             nucleoside analog anti-viral drug for 3 or more months; and (ii) have a serum
             hepatitis B virus (HBV) deoxyribonucleic acid (DNA) level of less than 100 IU/ml via
             polymerase chain reaction quantification assays prior to enrollment

          -  For patients with unknown hepatitis C virus ribonucleic acid (HCV antibody) status,
             must be tested during study screening; patients who are tested positive for HCV
             antibody are excluded from the study if they have inadequately controlled hepatitis C
             and/or Child-Pugh Class B or C cirrhosis; patients with adequately controlled
             hepatitis are not excluded from the study as defined by having undetectable level of
             serum HCV antibody level prior to enrollment; patients who are currently on interferon
             or other anti-HCV therapy will be excluded from study

          -  Active autoimmune disease or history of autoimmune disease that might recur, which may
             affect vital organ function or require immune suppressive treatment including systemic
             corticosteroids; NOTE: 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), 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; patients with vitiligo, endocrine
             deficiencies including thyroiditis managed with replacement hormones including
             physiologic corticosteroids are eligible; patients with rheumatoid arthritis and other
             arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and
             patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid
             antibodies should be evaluated for the presence of target organ involvement and
             potential need for systemic treatment but should otherwise be eligible

          -  Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus,
             residual hypothyroidism due to autoimmune condition only requiring hormone
             replacement, psoriasis not requiring systemic treatment, or conditions not expected to
             recur in the absence of an external trigger (precipitating event)

          -  Condition requiring systemic treatment with either corticosteroids (> 10 mg daily
             prednisone equivalents) or other immunosuppressive medications within 14 days of study
             drug administration; inhaled or topical steroids and adrenal replacement doses =< 10
             mg daily prednisone equivalents are permitted in the absence of active autoimmune
             disease; patients are permitted to use topical, ocular, intra-articular, intranasal,
             and inhalational corticosteroids (with minimal systemic absorption); physiologic
             replacement doses of systemic corticosteroids are permitted, even if =< 10 mg/day
             prednisone equivalents; a brief course of corticosteroids for prophylaxis (e.g.,
             contrast dye allergy) or for treatment of non-autoimmune conditions (e.g.,
             delayed-type hypersensitivity reaction caused by contact allergen) is permitted

          -  Evidence of active or acute (i.e. current, or recent within 4 weeks prior to
             registration) diverticulitis, intra-abdominal abscess, gastrointestinal (GI)
             obstruction and abdominal carcinomatosis which are known risk factors for bowel
             perforation; patients with abdominal carcinomatosis, a history of non-recent
             intra-abdominal abscess, or a history of non-recent GI obstruction should be evaluated
             for the potential need for additional treatment before coming on study