Nivolumab, Chemotherapy, and Radiation Therapy in Treating Patients with Locally Advanced Esophageal Squamous Cell Carcinoma

Inclusion Criteria

• Histologically or cytologically confirmed, treatment-naive esophageal squamous cell carcinoma
• Previously obtained archival tumor tissue, or tissue obtained by endoscopically guided core biopsy at screening
• Tany N1-3 or T3-4 N0 as determined by endoscopic ultrasound (EUS) or PET/CT; all palpable or CT/PET visible lymph nodes outside the usual surgical field must be biopsy-proven negative for cancer
• All patients must have locoregional staging determined by endoscopic ultrasound (EUS) if technically feasible; endoscopy reports or subsequent gastrointestinal (GI) clinic note should clearly state both the T and N stage
• All patients must have initial PET/CT scans to document no evidence of metastatic or unresectable squamous cell cancer
• All patients with tumors involving the thoracic esophagus must undergo bronchoscopy to document the absence of a fistula no known contraindication to the use of taxanes or platinum compounds
• No history of severe hypersensitivity reaction to Cremophor EL
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• A patient must be capable of giving informed consent or have an acceptable surrogate capable of giving consent on the subject’s behalf
• Deemed a suitable candidate for esophagectomy by the treating surgeon as documented in a pre-operative assessment visit per standard practice at each participating institution
• Deemed a suitable candidate for radiation therapy by the treating radiation oncologist as documented in a standard pretreatment visit per standard practice at each participating institution
• Patient must be non-pregnant and non-nursing; women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours prior to cycle 1 day 1 (C1D1)
• White blood cells (WBC) >= 2000/uL (obtained within 14 days prior to C1D1)
• Neutrophils >= 1500/uL (obtained within 14 days prior to C1D1)
• Platelets >= 100,000 4/uL (obtained within 14 days prior to C1D1)
• Hemoglobin > 9.0 g/dL (obtained within 14 days prior to C1D1)
• Serum creatinine =< 1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) >= 40 mL/min (obtained within 14 days prior to C1D1); calculated using the Cockcroft-Gault formula
• Aspartate aminotransferase (AST) =< 3 x ULN (obtained within 14 days prior to C1D1)
• Alanine aminotransferase (ALT) =< 3 x ULN (obtained within 14 days prior to C1D1)
• Total Bilirubin =< 1.5 x ULN , except subjects with Gilbert syndrome, who can have total bilirubin < 3.0 mg/dL (obtained within 14 days prior to C1D1)
• Oxygen saturation (O2 Sat.) >= 92% on ambient air (obtained within 14 days prior to C1D1)
• Rapid human immunodeficiency virus (HIV) 1/2 antibodies negative (obtained within 14 days prior to C1D1)
• Patients with a positive hepatitis B viral load are allowed on the study as long as patients are getting active treatment for hepatitis B on or prior to the first dose of treatment on this trial and continue throughout this trial
• All patients have to agree to participate in the correlative study of sample collection for immune correlative assays in order to participate in the main study; however, if the sample cannot be obtained due to feasibility issues, the patient will be allowed to continue on treatment

Exclusion Criteria

• T1-2 N0 as determined by EUS and PET/CT
• Pregnant or lactating women
• Active or prior documented autoimmune or inflammatory disorders including but not limited to inflammatory bowel disease; systemic lupus erythematosus; Wegener syndrome [granulomatosis with polyangiitis]; myasthenia gravis; Graves’ disease; rheumatoid arthritis, hypophysitis, uveitis) within the past 3 years prior to the start of treatment; the following are exceptions to this criterion: * Subjects with vitiligo or alopecia * Subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• The use of immunosuppressive medication within 28 days prior to the first dose of nivolumab; the following are exceptions to this criterion: * Intranasal, topical, inhaled corticosteroids or local steroid injections (e.g. intra-articular injection) * Systemic corticosteroids at physiologic doses =< 10 mg/day of prednisone or equivalent * Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication)
• Positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Active hepatitis B or hepatitis C (defined as positive-HBV surface antigen or detectable HCV-antibody); patients with a positive Hepatitis B core antibody (HBVcAb) must have negative viral load measurement
• Prior treatment with any immunotherapy
• Any other factors, including psychiatric or social, that in the opinion of the treating physician makes the patient an inappropriate candidate for a study
• Patients are excluded if they have active brain metastases or leptomeningeal metastases; subjects with brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for [lowest minimum is 4 weeks or more] after treatment is complete and within 28 days prior to the first dose of nivolumab administration; there must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration
• Patients should be excluded if they have an active, known or suspected autoimmune disease; subjects are permitted to enroll if they have vitiligo, 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
• Patients should be excluded if they have a 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
• As there is potential for hepatic toxicity with nivolumab or nivolumab non-drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen
• Patients with a history of allergy to the study drug components are excluded