Temozolomide With or Without Capecitabine in Treating Patients With Advanced Pancreatic Neuroendocrine Tumors

Prior treatment

• Prior temozolomide, dacarbazine (DTIC), or capecitabine, or 5-FU (fluorouracil) therapy
• Receiving any other investigational agents while on study treatment
• Receiving Coumadin while on treatment; other anticoagulants are allowed

Other illness

• Active or uncontrolled infection or serious medical or psychiatric illness
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or capecitabine
• Patients with a history of the following within 12 months of study entry:
  • Arterial thromboembolic events
  • Unstable angina
  • Myocardial Infarction
• Symptomatic peripheral vascular disease

Age

• Patients with previous or concurrent malignancy; exceptions are made for patients who meet any of the following conditions:
  • Non-melanoma skin cancer, in situ cervical cancer, or breast cancer in situ OR
  • Prior malignancy completely excised or removed and patient has been continuously disease free for \> 5 years OR
  • Prior malignancy cured by non-surgical modalities and patient has been continuously disease free for \> 5 years

Other

• Small cell carcinoma
• Patients with either clinically apparent central nervous system metastases or carcinomatous meningitis are ineligible
• Absorption issues that would limit the ability to absorb study agents
• Pregnant or breast-feeding

• Patient must have histologically or pathologically confirmed locally unresectable or metastatic low or intermediate grade pancreatic neuroendocrine tumor
• Patient must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria; baseline measurements and evaluations of all sites of disease must be obtained \<= 4 weeks prior to randomization and must be acquired by multiphasic CT or contrast magnetic resonance imaging (MRI)
• Date of last documented disease progression must be within 12 months from date of randomization
• Prior everolimus and/or sunitinib therapy is allowed, so long as it was discontinued \>= 4 weeks prior to randomization
• Concurrent somatostatin analogues are allowed provided that patients
  • Have been on a stable dose for 8 weeks and
  • Have documented disease progression on that dose
• Chemoembolization is allowed if ≥ 4 weeks from study entry. There are 2 possible scenarios:
  • If patient has hepatic disease only: they need to have progressed in the liver since chemoembolization and have measurable disease by RECIST 1.1 in order to be eligible.
  • If patient has hepatic and extrahepatic disease: they will need to have progressed inside OR outside the liver and have measureable disease by RECIST 1.1 in order to be eligible.
• Leukocytes \>= 3,000/mm\^3
• Absolute neutrophil count \>= 1,500/mm\^3
• Hemoglobin \>= 9 g/dL
• Platelets \>= 100,000/mm\^3
• Total bilirubin \<= institutional upper limit of normal (ULN) or \<= 1.5 X institutional ULN (if the patient has liver metastases)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \<= 3 X institutional ULN or (\<= 5 X institutional ULN if the patient has liver metastases)
• Serum creatinine \<= 1.5 X institutional ULN
• Patient must have Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Patient must have life expectancy \>= 12 weeks all females of childbearing potential must have a blood test or urine study within =\< 2 weeks prior to randomization to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:
  • Has not undergone a hysterectomy or bilateral oophorectomy; or
  • Has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
• Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study; should a woman become pregnant while participating in this study, she should inform her treating physician immediately; if a man impregnates a woman while participating in this study, he should inform his treating physician immediately
• Patient must be able to swallow pills
• Patient must be able to tolerate CT or magnetic resonance (MR) imaging including contrast agents as required for their treatment and the protocol