Regorafenib in Treating Patients With Advanced or Metastatic Neuroendocrine Tumors

This phase II trial studies regorafenib in treating patients with neuroendocrine tumors that have spread from the primary site (place where it started) to other places in the body. Regorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To assess progression-free survival (PFS) in advanced/metastatic in patients with carcinoid or pancreatic islet cell tumors.

SECONDARY OBJECTIVES:

I. To assess overall survival and response rate in advanced/metastatic poor prognosis in patients with carcinoid or pancreatic islet cell tumors.

II. To assess the toxicity of patients treated with regorafenib. III. To explore markers of angiogenesis as they relate to outcome in carcinoid and pancreatic islet cell tumors.

OUTLINE:

Patients receive regorafenib orally (PO) once daily (QD) on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Eligibility Criteria:
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 =\< 1.5 x the upper limits of normal (ULN)
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x ULN (=\< 5 x ULN for subjects with liver involvement of their cancer)
* Alkaline phosphastase limit =\< 2.5 x ULN (=\< 5 x ULN for subjects with liver involvement of their cancer)
* Lipase =\< 1.5 x the ULN
* Amylase =\< 1.5 x the ULN
* Serum creatinine =\< 1.5 x the ULN
* International normalized ratio (INR)/ partial thromboplastin time (PTT) \< 1.5 x ULN; (subjects who are treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists; close monitoring \[day 5 of cycle 1 and day 1 of each cycle\] is mandatory) will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care)
* Platelet count \>= 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 a non-healing wound, non-healing ulcer, or bone fracture
* Renal failure requiring hemo-or peritoneal dialysis
* Dehydration grade \>= 1 NCI-CTCAE v4.0
* Patients with seizure disorder requiring medication
* Persistent proteinuria \>= grade 3 NCI-CTCAE v4.0 (\> 3.5 g/24 hrs, measured by urine protein:creatinine ratio on a random urine sample)
* Interstitial lung disease with ongoing signs and symptoms at the time of informed consent
* Pleural effusion or ascites that causes respiratory compromise (\>= NCI-CTCAE version 4.0 grade 2 dyspnea)
* History of organ allograft (including corneal transplant)
* Known or suspected allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulations given during the course of this trial
* Any malabsorption condition
* Women who are pregnant or breast-feeding
* Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation
* Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results
* Patients with known brain metastases should be excluded from this clinical trial
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to regorafenib or other agents used in study
* 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
* Excluded therapies and medications, previous and concomitant

  * Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than study treatment (regorafenib)
  * Prior use of regorafenib
  * Concurrent use of chemotherapy, radiotherapy or another investigational drug or device therapy (i.e., outside of study treatment) during, or within 4 weeks of trial entry (signing of the ICF)
  * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication
  * Use of any herbal remedy (e.g. St. John's wort \[Hypericum perforatum\])