Daily Oral Regorafenib for Chemotherapy-Refractory, Metastatic and Locally Advanced Angiosarcoma

Inclusion Criteria:

* Life expectancy of at least 4 months
* Histologically confirmed angiosarcoma
* Tumor deemed unresectable or metastatic
* Measurable disease per RECIST v 1.1
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
* Progressive disease under last palliative therapy with a history of prior ifosfamide, doxorubicin or taxane therapy for angiosarcoma; up to 4 prior therapies are allowed
* All acute toxic effects of any prior treatment have resolved to grade 1 or less (by National Cancer Institute-Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] v 4.0) at the time of registration; NOTE: Exceptions to this criterion will include alopecia and fatigue
* 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 phosphatase limit =\< 2.5 x ULN (=\< 5 x ULN for subjects with liver involvement of their cancer)
* Lipase =\< 1.5 x the ULN
* Serum creatinine =\< 1.5 x the ULN
* International normalized ratio (INR)/partial thromboplastin time (PTT) \< 1.5 x ULN
* Platelet count \> 100000/mm\^3
* Hemoglobin \> 9 g/dL
* Absolute neutrophil count \> 1500/mm\^3
* If baseline urine protein creatinine (UPC) \>= 1, a 24-hour urine protein must be assessed; patients must have a 24-hour urine protein value \< grade 3 (\> 3.5 g/24 hours) to be eligible
* NOTE: Blood transfusion to meet the above criteria will not be allowed; NOTE: Patients who are prophylactically 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 of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care
* 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 age \>= 50 years and no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test
* Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at registration 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
* Subject must be able to swallow and retain oral medication
* Subjects must be able to understand and be willing to sign the written informed consent form; a signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure

Exclusion Criteria:

* Uncontrolled hypertension (systolic pressure \> 140 mmHg or diastolic pressure \> 90 mmHg on repeated measurement) despite optimal medical management
* Active or clinically significant cardiac disease including:

  * Congestive heart failure - New York Heart Association \> 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 registration, or myocardial infarction within 6 months before registration
* Evidence or history of bleeding diathesis or coagulopathy
* Any hemorrhage or bleeding event grade 3 within 4 weeks prior to registration
* 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 informed consent
* Subjects with any previously untreated or concurrent cancer unrelated to angiosarcoma; NOTE: Exceptions include 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 registration are allowed; all treatments must have been completed at least 3 years prior to registration
* Patients with pheochromocytoma
* Patients with severe hepatic impairment (Child-Pugh class C)
* 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
* Evidence of significant central nervous system disease including seizure disorder requiring medication, symptomatic metastatic brain or meningeal tumors
* Presence of a non-healing wound, non-healing ulcer, or bone fracture
* Renal failure requiring hemo-or peritoneal dialysis
* Dehydration \> grade 1
* Interstitial lung disease with ongoing signs and symptoms at the time of registration
* Pleural effusion or ascites that causes respiratory compromise (\>= 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
* Evidence of abdominal fistula, gastrointestinal (GI) perforation or intraabdominal abscess
* Women who are pregnant or breast-feeding
* Concurrent anti-cancer therapy (chemotherapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than study treatment (regorafenib)
* Prior use of regorafenib
* Prior use of sorafenib
* Use of cytotoxic chemotherapy within 21 days of registration
* Use of targeted therapy within two half-lives of registration
* Radiation directed at target lesion within 28 days of registration
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before registration
* Therapeutic anticoagulation with Vitamin-K antagonists (e.g., warfarin) or with heparins and heparinoids; NOTE: Prophylactic anticoagulation as described below is allowed:

  * Low dose warfarin (1 mg orally, once daily) with prothrombin time (PT)-international normalized ratio (INR) =\< 1.5 x ULN is permitted; infrequent bleeding or elevations in PT-INR have been reported in some subjects taking warfarin while on regorafenib therapy; therefore, subjects taking concomitant warfarin should be monitored regularly for changes in PT, PT-INR or clinical bleeding episodes
  * Low dose aspirin (=\< 100 mg daily)
  * Prophylactic doses of heparin
* 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