| 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 CD4 count will be allowed on study.
- Age = 18 years.
- ECOG performance status = 2 or Karnofsky performance score (KPS) = 50%
- Life expectancy of greater than 3 months.
- Absolute neutrophil count = 1,000/mcL
- Platelets = 75,000/mcL
- Total bilirubin = 1.5 X ULN
- AST (SGOT) / ALT (SGPT) = 2.5 X ULN
- Creatinine within normal institutional limit for the reference lab OR creatinine
clearance = 60 mL/min/1.73 m2 as calculated by Cockcroft-Gault formula for
participants with creatinine levels above institutional normal.
- Participants taking part in the optional biopsies must have cutaneous lesion(s)
amenable to two (2) 5-mm tumor biopsy at study entry and optional second biopsy on
therapy at week 8-12. Patients must have 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 ELISA test kit, and confirmed by Western blot or other approved
test, or HIV rapid multispot antibody differentiation assay). 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, participant must be on a stable antiretroviral
regimen for at least 12 weeks prior to study enrollment.
- There should be no evidence for improvement in Kaposi Sarcoma in the 3 months prior to
study enrollment, unless there is evidence for progression of Kaposi Sarcoma 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 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
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse events.
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to sEphB4-HSA or other agents used in study.
- Concurrent, acute, active infection, or treatment for infection, other than oral
thrush or genital herpes, within 14 days of enrollment. Mycobacterium avium complex
(MAC) that is undergoing treatment is allowed.
- Participants for whom front-line cytotoxic therapy is indicated (i.e. symptomatic
visceral or pulmonary Kaposi Sarcoma or symptomatic Kaposi Sarcoma 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.
- Pregnant women are excluded from this study because sEphB4-HSA has not been tested in
pregnant women and it could have potential 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 sEphB4-HSA, 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 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 systolic blood pressure >120 mm Hg or diastolic blood pressure >80
mm Hg who are unwilling to start antihypertensives (see Section 5.4 uncontrolled
sustained for recommendations for management of hypertension which will be defined as
during the study), or participants with systolic blood pressure > 140, and mm Hg, or
diastolic blood pressure > 90, even mm Hg, with or without use of anti-hypertensive
medications. (participants may not enroll onto the study until BP is = 140/90 mm Hg
with or without antihypertensives).
- 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 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
- 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.
- Patients with a history of CVA or TIA in the past 12 months
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