Phase II Study of Axitinib (AG-013736) With Evaluation of the VEGF-Pathway in Metastatic, Recurrent or Primary Unresectable Adrenocortical Cancer

* INCLUSION CRITERIA: 1. Pathologic confirmation of adrenocortical cancer by the Laboratory of Pathology, National Cancer Institute (NCI). 2. Measurable disease at presentation. 3. A life expectancy of at least 3 months and Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2. 4. Age greater than or equal to 18 years. 5. Last dose of chemotherapy or experimental therapy more than 4 weeks (6 weeks in the case of nitrosourea) prior to enrollment date; 2 weeks if the last therapy was received as part of a phase 0 or exploratory investigational new drug (IND) trial. Last surgery more than 4 weeks prior to enrollment, to allow for wound healing. Core biopsies or fine needle aspiration (FNA) will not require any waiting period. 6. Last radiotherapy treatment 4 weeks prior to starting treatment with this protocol and there must be sites of measurable disease that did not receive radiation. 7. Prior mitotane therapy is allowed. Patients with a history of a functional tumor who are receiving mitotane to control the excess hormone production may continue to receive mitotane. 8. Organ and marrow function as defined below: * Total bilirubin less than or equal to 1.5 x ULN (upper limit of normal), unless the patient meets the criteria for Gilbert's Syndrome. The upper limit value for bilirubin for subjects with Gilbert's Syndrome is less than 3 mg/dl. Note: A diagnosis of Gilbert's disease will be made in the presence of (1) unconjugated hyperbilirubinemia noted on several occasions; (2) normal results from complete blood count (CBC) count, reticulocyte count, and blood smear; (3) normal liver function test results; and (4) an absence of other disease processes that can explain the unconjugated hyperbilirubinemia. * Aspartate aminotransaminase (AST) less than or equal to 2.5 times ULN, alanine aminotransaminase (ALT) greater than or equal to 2.5 times ULN * Amylase and lipase equal to, or less than, the institutional ULN. * Creatinine clearance greater than or equal to 40 ml/min (measured in a timed urine collection) or serum creatinine less than or equal to 1.6 mg/dl * Absolute neutrophil count greater than or equal to 1000/mm\^3. * Platelet count greater than or equal to 100,000/ mm\^3. 9\. Ability to understand and sign an informed consent document. 10\. Ability and willingness to follow the guidelines of the clinical protocol including visits to NCI, Bethesda, Maryland for treatment and follow up visits. 11\. Because the effects of chemotherapy on the developing human fetus are potentially harmful, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier methods) before, during the study and for a period of 3 months after the last dose of chemotherapy. EXCLUSION CRITERIA: 1. Patients with adrenocortical tumors potentially curable by surgical excision alone as determined by the Principal Investigator in discussions with the surgical consultants. 2. Patients who have large abdominal masses impinging on bowel or pulmonary masses with encroached vessels and a potential to bleed will be considered on case by case basis after careful consultation with multiple disciplines such as radiologists and surgeons with main intent being patient safety. 3. Unstable hypertension defined as a systolic blood pressure greater than 140 mm Hg or diastolic pressure greater than 90 mmHg despite optimal medical management and patients who are receiving more than 1 antihypertensive agent at trial entry, (not including spironolactone) unless the patient has Cushing's Disease with its associated hypertension and is well controlled on medications. 4. Untreated brain metastases (or local treatment of brain metastases within the last 6 months) due to the poor prognosis of these patients and difficulty ascertaining the cause of neurologic adverse events. 5. Pregnancy, due to the possible adverse effects on the developing fetus. 6. Lactating women who are breast-feeding due to the possibility of transmitting axitinib to the child. 7. The presence of a second malignancy, other than a skin cancer or in situ cervical cancer because it will complicate the primary objective of the study. Cancer survivors who have been free of disease for at least two years can be enrolled in this study. 8. Patients with evidence of a bleeding diathesis. 9. Phosphorus level equal to, or less than, the institutional lower limits of normal that cannot be corrected. 10. Gastrointestinal abnormalities including: 1. inability to take oral medications 2. requirement for intravenous alimentation 3. prior surgical procedure affecting absorption including total gastric resection 4. treatment for active peptic ulcer disease in the past 6 months 5. active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy 6. malabsorption syndrome 11. Current use or anticipated need for treatment with drugs that are known potent cytochrome P450 3A4 (CYP3A4) inhibitors (i.e., grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, telithromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, and delavirdine). 12. Current use or anticipated need for treatment with drugs that are known CYP3A4 inducers (i.e., carbamazepine, Phenobarbital, phenytoin, amobarbital, nevirapine, primidone, rifabutin, rifampin, and St. John's wort). 13. Requirement of anticoagulant therapy with oral vitamin K antagonists. Low-dose anticoagulants for maintenance of patency of central venous access devise or prevention of deep venous thrombosis is allowed. Therapeutic use of low molecular weight heparin is allowed. 14. Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis. 15. Any of the following within 12 months prior to study drug administration: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack and 6 months for deep vein thrombosis or pulmonary embolism. 16. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study. 17. Current use of drugs that are known inhibitors or inducers of Breast Cancer Resistance Protein (BCRP) and Organic Anion Transporting Polypeptide (OATP)1B1/3 or known to affect protein binding should be used with caution and with acknowledgement of the principal investigator (PI).