The main purpose of this study is to see whether Axitinib will help prolong the time that the patient's carcinoid tumors remain stable, and to examine their treatment response through testing. Researchers also want to find out if Axitinib is safe and tolerable.

This is a bi-institutional, prospective phase II, open-label study. The target population is comprised of adult patients with histologically confirmed unresectable or metastatic carcinoid tumors. Carcinoid tumors are defined as well to moderately differentiated neuroendocrine tumors of the digestive tract and lungs. Patients with metastatic carcinoid tumors of unknown primary as well as rare primaries (renal, ovarian, thymic, hepatic) will also be eligible. Patients will be drawn from two institutions Moffitt Cancer Center (MCC) and The University of California, San Francisco (UCSF).

Inclusion Criteria:

• Locally unresectable or metastatic well-and moderately-differentiated (low- or intermediate- grade) neuroendocrine tumors of the aerodigestive tract (e.g. foregut, midgut, and hindgut) and unknown primary site as well as rare primary sites (renal, ovarian, thymic, hepatic); Otherwise known as typical or atypical carcinoid tumors
• Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) Criteria
• Functional or nonfunctional tumors allowed
• Evidence of progressive disease within 12 months of study entry
• Adequate hepatic function: total bilirubin ≤1.5 x upper limit of normal (ULN)mg/dl; aspartic transaminase (AST) ≤2.5 x ULN (≤5 x ULN if attributable to liver metastases)
• Adequate renal function: serum creatinine ≤ 1.5 x ULN
• Adequate bone marrow function: absolute neutrophil count ≥ 1,500/mm³; platelets ≥75,000/mm³
• Prothrombin time (PT) and activated partial thromboplastin time (aPTT) levels ≤1.5 x ULN (unless patients receiving coumadin anticoagulation in which case a stable international normalization ration (INR) of 2-3 is required).
• Urine protein <2+proteinuria (or <2 g proteinuria /24 hr)
• Prior somatostatin-analog therapy required in patients with midgut carcinoid tumors
• Minimum 4 weeks since completion of prior treatment (investigational or other). Prior treatment with chemotherapy, radiotherapy, hepatic artery embolization, surgery or other therapeutic agents is allowed.
• Treatment related toxicity should have returned to baseline and/or ≤grade 1 prior to study treatment.
• Prior or concurrent therapy with somatostatin analogs is permitted for the control of hormone-mediated symptoms, provided patient has been on a stable dose for at least 2 months and progressive disease on somatostatin analogs (SSTa) has been documented
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to treatment.
• Ability to sign informed consent
• Willingness and ability to comply with scheduled visits, laboratory tests and other study procedures

Exclusion Criteria:

• Poorly differentiated, high-grade (e.g. small cell or large cell) neuroendocrine carcinomas are excluded.
• Pancreatic neuroendocrine tumors (NETs), paragangliomas, pheochromocytomas and medullary thyroid cancers are excluded.
• Adenocarcinoid tumors and goblet cell carcinoid tumors are excluded.
• Prior antiangiogenic therapy with a dedicated vascular endothelial growth factor (VEGF) pathway inhibitor
• Clinically apparent central nervous system metastases
• Any of the following within 12 months prior to study: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack
• Deep venous thrombosis or pulmonary embolism within 6 months of study
• Major surgery 4 weeks prior to enrollment
• Inability to take oral medication or prior surgical procedures affecting absorption (including total gastric resection)
• Active gastrointestinal bleeding, if transfusion dependent
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
• History of pulmonary hemorrhage or evidence of significant hemoptysis
• History of serious non-healing wound, ulcer, or bone fracture within the past 28 days
• Pre-existing thyroid abnormality allowed provided thyroid function can be controlled with medication.
• Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (i.e. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, etc.)
• Current use or anticipated need for treatment with drugs that are known inducers of CYP3AR or CYP1A2 (i.e carbamazepine, dexamethasone, omeprazole, phenobarbital, phenytoin, rifampin, St. John's Wart, etc.)
• Uncontrolled serious medical or psychiatric illness. Patients with a "currently active" second malignancy other than non-melanoma skin cancers, carcinoma in situ of the cervix, resected incidental prostate cancer (staged pathological tumor-2 (pT2) with Gleason Score ≤ 6 and postoperative prostatic specific antigen (PSA) < 0.5 ng/mL), or other adequately treated carcinoma-in-situ are ineligible. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for ≥3 years.
• Pregnant or lactating women, or adults of reproductive potential who are not using effective birth-control methods.
• Prior antitumor therapy within 4 weeks of enrollment (with exception of somatostatin analogs)
• Liver-directed therapy within 2 months of enrollment. Prior treatment with radiotherapy (including radio-labeled spheres and/or cyberknife, hepatic arterial embolization (with or without chemotherapy) or cryotherapy/ablation is allowed if these therapies did not affect the areas of measurable disease being used for this protocol or if progressive disease can be documented in the previously treated area.
• Recent infection requiring systemic anti-infective treatment that was completed ≤14 days prior to enrollment (with the exception of uncomplicated urinary tract infection or upper respiratory tract infection)
• Uncontrolled hypertension (blood-pressure >140/90). Patient with baseline hypertension may be eligible after initiation of antihypertensive therapy.

All participants.

3 years, 10 months

Results are limited by a relatively high rate of participant withdrawal before progression due to toxicity. Post analysis, 2 participants are still on study at UCSF.