sEphB4-HSA in Treating Patients With Kaposi Sarcoma

Inclusion Criteria: * Participants may be treatment naïve, refractory to or intolerant of one or more prior therapies, or treated with prior systemic treatment including but not limited to liposomal doxorubicin * Participants must have biopsy-proven KS involving skin with or without visceral involvement * If HIV-positive, any cluster of differentiation (CD)4 count will be allowed on study * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 or Karnofsky performance score (KPS) \>= 60% * Life expectancy of greater than 3 months * Absolute neutrophil count \>= 1,500/mcL\* * Participants may be receiving growth factor support to meet these criteria * Platelets \>= 100,000/mcL * Total bilirubin =\< 1.5 x upper limit of normal (ULN) * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN * Creatinine within normal institutional limit for the reference lab OR creatinine clearance \>= 60 mL/min/1.73 m\^2 as calculated by Cockcroft-Gault formula for participants with creatinine levels above institutional normal * Participants must have cutaneous lesion(s) amenable to four (4) 5-mm tumor biopsies during the study (either 4 separate lesions measuring \>= 5 mm each OR 2 separate lesions measuring \>= 10 mm each) and at least five additional lesions measurable for assessment with no improvement over the past month * Females of childbearing potent…