Combination Chemotherapy in Treating Patients with Metastatic High Grade Neuroendocrine Carcinoma of the Gastrointestinal Tract or Pancreas

Inclusion Criteria

• Patients must have histologically or cytologically confirmed neuroendocrine carcinoma of the gastrointestinal (GI) tract; patients with unknown origin for the neuroendocrine carcinoma in which a gastroenteropancreatic origin is suspected (per pathologist or investigator discretion) will be eligible for the study
• Tumors must have a Ki-67 index greater than 20% and/or > 20 mitotic figures/10 high-power fields
• Patients must have metastatic disease
• Patients must measurable disease, as defined by RECIST 1.1 criteria
• Any line of treatment (first line versus beyond first line)
• Life expectancy of greater than 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Absolute neutrophil count >= 1,500/mm^3
• Platelets >= 100,000/mm^3
• Total bilirubin =< 1.5 X institutional upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 X institutional upper limit of normal
• Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Patients who have had chemotherapy or radiotherapy within 3 weeks prior to entering the study
• Patients may not be receiving any other investigational agents
• Patients with untreated brain or meningeal metastases
• Prior treatment with 5-fluorouracil, irinotecan or oxaliplatin
• Patients with pre-treatment peripheral neuropathy greater than grade 1 per the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 will be excluded
• 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
• Patients with a secondary primary cancer (excluding baso/squamous cell carcinoma of skin) within 1 year will be excluded
• Active viral hepatitis or autoimmune hepatitis; the work-up to confirm active hepatitis or autoimmune hepatitis will only be done if clinical suspicion based on investigator discretion
• Patients with childbearing potential who are not willing to use adequate contraception precautions during the study and for 3 months after stopping study chemotherapy * Women of childbearing potential (and men) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; female patients of childbearing age will be required to have a negative pregnancy test within a week prior to consenting for study * All women are considered of childbearing potential, unless they meet at least one of the following criteria: ** Females who are menopausal, defined as follows: i) females who are younger than 55 years old will be considered menopausal if they satisfy all the following three requirements during screening: 1) they are in amenorrhea, defined as absence of menstruation for the previous 12 months; 2) they have a negative urine pregnancy test; and 3) they have a serum follicle-stimulating hormone (FSH) level within the laboratory reference range for postmenopausal females; ii) females who are older than 55 years old: they will be considered menopausal if they are in amenorrhea, defined as absence of menstruation for the previous 12 months before screening ** Females who have a documented hysterectomy and/or bilateral oophorectomy and/or tubal ligations * All men are considered of childbearing potential, unless they meet at least one of the following criteria: ** Males who have a documented vasectomy more than 6 months prior to the administration of the first study treatment. ** Female partner/partners who are menopausal (as previously defined) and/or who have a documented hysterectomy and/or bilateral oophorectomy and/or tubal ligations