Cabozantinib for Adults With Advanced Soft Tissue Sarcoma

* INCLUSION CRITERIA: * Patients must have histologically or cytologically confirmed soft tissue sarcoma that is metastatic or unresectable and for which standard treatment that prolongs survival does not exist or is no longer effective. * Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>20 mm with conventional techniques or as \>10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam. * Patients are allowed prior vascular endothelial growth factor receptor (VEGFR)-tyrosine kinase inhibitors (TKI) therapy. * Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of cabozantinib in patients \<18 years of age, children are excluded from this study. * Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1 (Karnofsky \>70%). * Life expectancy \> 3 months. * Patients must have normal organ and marrow function as defined below: * leukocytes greater than or equal to 3,000/mcL * absolute neutrophil count greater than or equal to 1,500/mcL * platelets greater than or equal to 100,000/mcL * total bilirubin less than or equal to 1.5 times ULN * Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase(SGOT)/alanine aminotransferase (ALT) serum glutamic pyruvic transaminase(SGPT) less than or equal to 2.5 times institutional upper limit of normal creatinine within normal institutional limits * creatinine within normal institutional limits OR clearance greater than or equal to 60 mL/min/1.73 m(2) for patients with creatinine levels above institutional normal. * hemoglobin greater than or equal to 9 g/dL * serum albumin greater than or equal to 2.8g/dL * lipase \<2.0 times upper limit of normal (ULN) and no radiologic or clinical evidence of pancreatitis * urine protein/creatinine ratio (UPCR) less than or equal to 1 * serum phosphorus calcium, magnesium and potassium greater than or equal to lower limit of normal (LLN) * Subjects must have blood pressure (BP) no greater than 140 mmHg (systolic) and 90 mmHg (diastolic) for eligibility. Initiation or adjustment of BP medication is permitted prior to study entry provided that the average of three BP readings at the time of enrollment is less than or equal to 140/90 mmHg * Patients must be able to swallow whole tablets. Tablets must not be crushed or chewed. * The effects of cabozantinib on the developing human fetus are unknown. For this reason and because receptor tyrosine kinases are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception. All subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of the study and for 4 months after the last dose of study drug(s). Sexually active subjects (men and women) must agree to use medically accepted barrier methods of contraception (e.g., male or female condom) during the course of the study and for 4 months after the last dose of study drug(s), even if oral contraceptives are also used. -Ability to understand and the willingness to sign a written informed consent document. EXCLUSION CRITERIA: * Patients who have had anticancer therapy, including kinase inhibitors or any investigational agent within 4 weeks or 5 half-lives (whichever is shorter) (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered to baseline from adverse events (except alopecia and other non-clinically significant adverse events (AEs). Patients who have received prior cabozantinib or inhibitors of tyrosine-protein kinase mesenchymal epithelial transition factor (c-MET) or hepatocyte growth factor (HGF) are ineligible. * The subject has received radionuclide treatment within 6 weeks of the first dose of study treatment * The subject has received radiation therapy within 4 weeks (greater than or equal to 2 weeks for palliative radiation therapy) * Patients with active brain metastases or carcinomatous meningitis or epidural disease are excluded from this clinical trial. Subjects with brain metastases previously treated with whole brain radiation or radiosurgery or subjects with epidural disease previously treated with radiation who are asymptomatic and have remained stable for 4 weeks and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible. Neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment. Baseline brain imaging with contrast-enhanced CT or MRI scans for subjects with known brain metastases is required to confirm eligibility. * Eligibility of subjects receiving any medications or substances known to affect or with the potential to affect the activity of cabozantinib will be determined following review of their cases by the Principal Investigator. Patients who are taking enzyme-inducing anticonvulsant agents are not eligible. * Patients with refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that could interfere with absorption. * Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant women are excluded from this study because cabozantinib has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cabozantinib, breastfeeding should be discontinued if the mother is treated with cabozantinib. * Strong inhibitors and inducers of cytochrome P450 3A4 (CYP3A4) can affect levels of cabozantinib and should be avoided whenever possible or switched to alternatives. Subjects requiring chronic concomitant treatment of strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's Wort) are not eligible for this study. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/; medical reference texts such as the Physicians Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over the-counter medicine or herbal product. * Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with cabozantinib. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated. * The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or Factor Xa inhibitors, or antiplatelet agents (e.g., clopidogrel). Low dose aspirin (less than or equal to 81 mg/day), low-dose warfarin (less than or equal to 1 mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted. (Please note that there may be cases in which patients on study require anticoagulation for deep vein thrombosis (DVT)/pulmonary embolism (PE) management; this does not necessitate taking the patient off study.) * The subject has experienced any of the following * clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment * hemoptysis of greater than or equal to 0.5 teaspoon (2.5 mL) of red blood within 3 months before the first dose of study treatment * any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment * The subject has radiographic evidence of cavitating pulmonary lesion(s). * The subject has tumor in contact with, invading, or encasing any major blood vessels * The subject has evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib * The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: 1. Cardiovascular disorders including: 1. Congestive heart failure (CHF): New York Heart Association (NYHA) Class III (moderate) or Class IV (severe) at the time of screening 2. Concurrent uncontrolled hypertension defined as sustained BP \> 140 mm Hg systolic, or \> 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment 3. Any history of congenital long QT syndrome 4. Any of the following within 6 months before the first dose of study treatment: * unstable angina pectoris * clinically-significant cardiac arrhythmias * stroke (including transient ischemic attack (TIA), or other ischemic event) * myocardial infarction * thromboembolic event requiring therapeutic anticoagulation (Note: subjects with a venous filter (e.g. vena cava filter) are not eligible for this study) 2. Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including: 1. Any of the following within 28 days before the first dose of study treatment * intra-abdominal tumor/metastases invading GI mucosa * active peptic ulcer disease, * inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis * malabsorption syndrome 2. Any of the following within 6 months before the first dose of study treatment: * abdominal fistula * gastrointestinal perforation * bowel obstruction or gastric outlet obstruction * intra-abdominal abscess. Note: Complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more that 6 months before the first dose of study treatment. 3. Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the first dose of study therapy 4. Other clinically significant disorders such as: 1. serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment 2. history of organ transplant, including allogeneic bone marrow transplant 3. concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment 4. history of major surgery as follows: i. Major surgery within 3 months of the first dose of cabozantinib if there were no wound healing complications or within 6 months of the first dose of cabozantinib if there were wound complications ii. Minor surgery within 1 months of the first dose of cabozantinib if there were no wound healing complications or within 3 months of the first dose of cabozantinib if there were wound complications In addition, complete wound healing from prior surgery must be confirmed at least 28 days before the first dose of cabozantinib irrespective of the time from surgery * The subject is unable to swallow tablets * The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) \>500 ms within 28 days before enrollment. Note: if initial QTcF is found to be \> 500 ms, two additional EKGs separated by at least 3 minutes should be performed. If the average of these three consecutive results for QTcF is less than or equal to 500 ms, the subject meets eligibility in this regard. * The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee. * The subject has had evidence within 2 years of the start of study treatment of another malignancy which required systemic treatment. * Patients should not have any clinical evidence of an active infection at the time of enrollment. INCLUSION OF WOMEN AND MINORITIES: Both men and women of all races and ethnic groups are eligible for this trial.