sEphB4-HSA in Treating Patients With Kaposi Sarcoma

Inclusion Criteria:

• Participants may be treatment naïve, refractory to or intolerant of one or moreprior therapies, or treated with prior systemic treatment including but not limitedto liposomal doxorubicin

• Participants must have biopsy-proven KS involving skin with or without visceralinvolvement

• If HIV-positive, any cluster of differentiation (CD)4 count will be allowed on study

• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 or Karnofskyperformance 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 creatinineclearance >= 60 mL/min/1.73 m^2 as calculated by Cockcroft-Gault formula forparticipants with creatinine levels above institutional normal

• Participants must have cutaneous lesion(s) amenable to four (4) 5-mm tumor biopsiesduring the study (either 4 separate lesions measuring >= 5 mm each OR 2 separatelesions measuring >= 10 mm each) and at least five additional lesions measurable forassessment with no improvement over the past month

• Females of childbearing potential (FCBP)* must have a negative serum or urinepregnancy test with a sensitivity of at least 25 mIU/mL within 14 days prior toenrollment and again within 24 hours prior to starting cycle 1 of sEphB4-HSA;further, they must either commit to continued abstinence from heterosexualintercourse or begin TWO acceptable methods of birth control: one highly effectivemethod and one additional effective method AT THE SAME TIME during receipt ofsEphB4-HSA, and 12 weeks after discontinuation of sEphB4-HSA; FCBP must also agreeto ongoing pregnancy testing; men must agree to use a latex condom during sexualcontact with a FCBP even if they have had a successful vasectomy

• A female of childbearing potential is a sexually mature woman who: 1) has notundergone a hysterectomy or bilateral oophorectomy; or 2) has not beennaturally postmenopausal for at least 24 consecutive months (i.e., has hadmenses at any time in the preceding 24 consecutive months)

• Documentation of HIV status; if participant is HIV positive, HIV-1 infection, asdocumented by any federally approved, licensed HIV rapid test performed inconjunction with screening (or enzyme-linked immunosorbent assay [ELISA], test kit,and confirmed by Western blot or other approved test); alternatively, thisdocumentation may include a record demonstrating that another physician hasdocumented the participant's HIV status based on either: 1) approved diagnostictests, or 2) the referring physician's written record that HIV infection wasdocumented, with supporting information on the participant's relevant medicalhistory and/or current management of HIV infection

• If the participant is HIV negative, documentation of a negative result for anyfederally approved, licensed HIV rapid test within 4 weeks prior to studyenrollment will suffice; if the initial rapid test is positive, furtherapproved confirmatory test results must be present to document the subject'sHIV status

• If participant is HIV positive, participants must be on a stable antiretroviralregimen for at least 12 weeks prior to study enrollment

• There should be no evidence for improvement in KS in the 3 months prior to studyenrollment, unless there is evidence for progression of KS in the 4 weeksimmediately prior to study enrollment

• Participants must, in the opinion of the investigator, be capable of complying withthe protocol

Exclusion Criteria:

• Inability to understand and inability to provide informed consent

• Participants who are receiving any other investigational agents

• Participants who have had anti-neoplastic treatment for KS (including chemotherapy,radiotherapy, local treatment including topical fluorouracil [5-FU], biologicaltherapy or investigational therapy) within 4 weeks (6 weeks for nitrosoureas ormitomycin C) prior to entering the study OR those who have not recovered fromadverse events due to agents administered more than 4 weeks earlier

• Participants with known brain metastases should be excluded from this clinical trial

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition to sEphB4-HSA or other agents used in study

• Participants who refuse antiretroviral therapy for HIV, if HIV positive

• Concurrent, acute, active infection, or treatment for infection, other than oralthrush or genital herpes, within 14 days of enrollment

• Participants for whom front-line cytotoxic therapy is indicated (i.e. symptomaticvisceral or pulmonary KS or symptomatic KS impairing functional status)

• Concurrent neoplasia requiring cytotoxic therapy

• Participant is =< 2 years free of another primary malignancy; exceptions include thefollowing:

• Basal cell skin cancer

• Cervical carcinoma in situ

• Anal carcinoma in situ

• Any steroid treatment except for that required for replacement therapy in adrenalinsufficiency, topical or injected testosterone for hypogonadism, or inhaledsteroids for the treatment of asthma

• Previous local therapy of any KS-indicator lesion unless the lesion has clearlyprogressed since that local treatment; any prior local treatment to indicatorlesions regardless of the elapsed time should not be allowed unless there isevidence of clear-cut progression of said lesion

• Female participants who are pregnant, lactating, or breast-feeding

• Breastfeeding should be discontinued if the mother is treated with sEphB4-HSA

• Participants with a recent history (< 6 months) of a major infarct including but notinclusive to bowel ischemia, cerebral vascular accident, transient ischemic attack,myocardial infarction, limb ischemia, or skin necrosis

• Participants with a QTcF (Fridericia correction formula) > 480 ms on 2 out of 3electrocardiograms (EKGs) (if first EKG is < 480, no need to repeat, if first EKG is > 480 repeat twice for a total of 3 EKGs)

• Participants with uncontrolled sustained hypertension which will be defined assystolic blood pressure > 140, and diastolic blood pressure > 90, even with use ofanti-hypertensive medications

• Participants with a recent history (< 6 months) of a major bleed which will bedefined as a symptomatic bleeding in a critical area or organ, such as intracranial,intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, orintramuscular with compartment syndrome, and/or bleeding causing a fall inhemoglobin level 2 grams/dL or more, or leading to transfusion of two or more unitsof whole blood or packed red cells

• Participants on any dose of warfarin or are on full dose anticoagulation with otheragents including low molecular weight heparin, antithrombin agents, antiplateletagents and full dose aspirin within 7 days prior to study enrollment; participantson prophylactic doses of low molecular weight heparin and low dose anticoagulantsare allowed.

• Cardiac related illnesses including, but not limited to:

• Symptomatic congestive heart failure including participants with grade III/IVcardiac disease as defined by the New York Heart Association functionalcriteria

• Unstable angina pectoris

• Cardiac arrhythmia

• Proteinuria as defined as > 2+ on urine dipstick; if dipstick urinalysis shows >= 2+proteinuria, 24-hour urine for protein must be < 2 grams

• Participants with diabetes mellitus with ketoacidosis or chronic obstructivepulmonary disease (COPD) requiring hospitalization in the preceding 6 months, or anyother intercurrent medical condition that contraindicates treatment with sEphB4-HSAor places the participant at undue risk for treatment related complications

• Physical or psychiatric illness/social situations that in the estimation of theinvestigator would limit compliance with study requirements or place the participantat high risk of toxicity or non-compliance