Regorafenib in Treating Patients With Advanced or Metastatic Neuroendocrine Tumors

Inclusion Criteria

• Advanced metastatic, progressing carcinoid or pancreatic islet cell cancers
• No prior targeted treatment (tx) or anti-angiogenic therapy; patients may have received one line of prior therapy with octreotide, locoregional therapy; continuation of concurrent octreotide is allowed; patients will be maintained on octreotide (sandostatin) for the duration of their treatment
• Life expectancy of at least 12 weeks (3 months)
• Subjects must be able to understand and be willing to sign the written informed consent form (ICF); a signed ICF must be appropriately obtained prior to the conduct of any trial-specific procedure
• All acute toxic effects of any prior treatment have resolved to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version (v)4.0 grade 1 or less at the time of signing the informed consent form (ICF); exceptions to this include alopecia
• Total bilirubin = = 100,000 /mm^3
• Hemoglobin (Hb) >= 9 g/dL
• Absolute neutrophil count (ANC) >= 1, 500/mm^3; blood transfusion to meet the inclusion criteria will not be allowed
• Glomerular filtration rate (GFR) >= 30 ml/min/1.73 m^2 according to the Modified Diet in Renal Disease (MDRD) abbreviated formula
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug; post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test; the definition of adequate contraception will be based on the judgement of the investigator
• Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the ICF until at least 3 months after the last dose of study drug; the definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate
• Subject must be able to swallow and retain oral medication
• Southwest Oncology Group (SWOG) performance status 0-1
• Patients must have measurable disease

Exclusion Criteria

• Previous assignment to treatment during this study; subjects permanently withdrawn from study participation will not be allowed to re-enter study
• Uncontrolled hypertension (systolic pressure > 140 mm Hg or diastolic pressure > 90 mm Hg [NCI-CTCAE v4.0] on repeated measurement) despite optimal medical management
• Active or clinically significant cardiac disease including:
• Congestive heart failure - New York Heart Association (NYHA) > class II
• Active coronary artery disease
• Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin
• Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before randomization, or myocardial infarction within 6 months before randomization
• Evidence or history of bleeding diathesis or coagulopathy
• Any hemorrhage or bleeding event >= NCI-CTCAE grade 3 within 4 weeks prior to start of study medication
• Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) deep vein thrombosis or pulmonary embolism within 6 months of start of study treatment
• Subjects with any previously untreated or concurrent cancer that is distinct in primary site or histology from carcinoid or pancreatic islet cancer except cervical cancer in-situ, treated basal cell carcinoma, or superficial bladder tumor; subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before randomization are allowed; all cancer treatments must be completed at least 3 years prior to study entry (i.e., signature date of the informed consent form)
• Patients with pheochromocytoma
• Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy
• Ongoing infection > grade 2 NCI-CTCAE v4.0
• Presence of