| Eligibility |
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 potential (FCBP)* must have a negative serum or urine
pregnancy test with a sensitivity of at least 25 mIU/mL within 14 days prior to
enrollment and again within 24 hours prior to starting cycle 1 of sEphB4-HSA; further,
they must either commit to continued abstinence from heterosexual intercourse or begin
TWO acceptable methods of birth control: one highly effective method and one
additional effective method AT THE SAME TIME during receipt of sEphB4-HSA, and 12
weeks after discontinuation of sEphB4-HSA; FCBP must also agree to ongoing pregnancy
testing; men must agree to use a latex condom during sexual contact with a FCBP even
if they have had a successful vasectomy
- A female of childbearing potential is a sexually mature woman who: 1) has not
undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally
postmenopausal for at least 24 consecutive months (i.e., has had menses at any
time in the preceding 24 consecutive months)
- Documentation of HIV status; if participant is HIV positive, HIV-1 infection, as
documented by any federally approved, licensed HIV rapid test performed in conjunction
with screening (or enzyme-linked immunosorbent assay [ELISA], test kit, and confirmed
by Western blot or other approved test); alternatively, this documentation may include
a record demonstrating that another physician has documented the participant's HIV
status based on either: 1) approved diagnostic tests, or 2) the referring physician's
written record that HIV infection was documented, with supporting information on the
participant's relevant medical history and/or current management of HIV infection
- If the participant is HIV negative, documentation of a negative result for any
federally approved, licensed HIV rapid test within 4 weeks prior to study
enrollment will suffice; if the initial rapid test is positive, further approved
confirmatory test results must be present to document the subject's HIV status
- If participant is HIV positive, participants must be on a stable antiretroviral
regimen for at least 12 weeks prior to study enrollment
- There should be no evidence for improvement in KS in the 3 months prior to study
enrollment, unless there is evidence for progression of KS in the 4 weeks immediately
prior to study enrollment
- Participants must, in the opinion of the investigator, be capable of complying with
the 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], biological
therapy or investigational therapy) within 4 weeks (6 weeks for nitrosoureas or
mitomycin C) prior to entering the study OR those who have not recovered from adverse
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 or biologic
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 oral
thrush or genital herpes, within 14 days of enrollment
- Participants for whom front-line cytotoxic therapy is indicated (i.e. symptomatic
visceral 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 the
following:
- Basal cell skin cancer
- Cervical carcinoma in situ
- Anal carcinoma in situ
- Any steroid treatment except for that required for replacement therapy in adrenal
insufficiency, topical or injected testosterone for hypogonadism, or inhaled steroids
for the treatment of asthma
- Previous local therapy of any KS-indicator lesion unless the lesion has clearly
progressed since that local treatment; any prior local treatment to indicator lesions
regardless of the elapsed time should not be allowed unless there is evidence 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 not
inclusive 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 3
electrocardiograms (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 as
systolic blood pressure > 140, and diastolic blood pressure > 90, even with use of
anti-hypertensive medications
- Participants with a recent history (< 6 months) of a major bleed which will be defined
as a symptomatic bleeding in a critical area or organ, such as intracranial,
intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or
intramuscular with compartment syndrome, and/or bleeding causing a fall in hemoglobin
level 2 grams/dL or more, or leading to transfusion of two or more units of whole
blood or packed red cells
- Participants on any dose of warfarin or are on full dose anticoagulation with other
agents including low molecular weight heparin, antithrombin agents, antiplatelet
agents and full dose aspirin within 7 days prior to study enrollment; participants on
prophylactic doses of low molecular weight heparin and low dose anticoagulants are
allowed.
- Cardiac related illnesses including, but not limited to:
- Symptomatic congestive heart failure including participants with grade III/IV
cardiac disease as defined by the New York Heart Association functional criteria
- 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 obstructive pulmonary
disease (COPD) requiring hospitalization in the preceding 6 months, or any other
intercurrent medical condition that contraindicates treatment with sEphB4-HSA or
places the participant at undue risk for treatment related complications
- Physical or psychiatric illness/social situations that in the estimation of the
investigator would limit compliance with study requirements or place the participant
at high risk of toxicity or non-compliance
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