Summary

This phase II trial studies sEphB4-HSA in treating patients with Kaposi sarcoma. sEphB4-HSA protein may block the growth of blood vessels that provide blood to the cancer, and may also prevent cancer cells from growing.

Objectives

PRIMARY OBJECTIVE:
I. To evaluate the clinical response and toxicity of recombinant EphB4-HSA fusion protein (sEphB4-HSA) (at initial dosing of 10 mg/kg every 2 weeks) in participants with Kaposi sarcoma.

SECONDARY OBJECTIVES:
I. To assess the safety of sEphB4-HSA in participants with Kaposi sarcoma (KS).
II. To determine trough level exposure of sEphB4-HSA and correlate with tumor response.
III. To characterize the pharmacodynamics of sEphB4-HSA and correlate these effects with clinical response.
IIIa. Effects on viral replication and gene expression of human herpes virus-8 (HHV-8).
IIIb. Changes in vascular endothelial growth factor (VEGF)-Notch-EphrinB2 angiogenic pathway.
IIIc. Effects on immune response and modulation.
IIId. Effects on tumor cell apoptosis and proliferation.
IIIe. Effects on sEphB4-HSA on human immunodeficiency virus (HIV) plasma viral loads in participants with HIV.
IV. To archive peripheral blood mononuclear cells (PBMCs) and tissue samples to be used in conjunction with samples collected in subsequent trials of sEphB4-HSA for future studies including identification of biomarkers predictive of response.

EXPLORATORY OBJECTIVE:
I. Describe baseline quality of life (QOL) scores, using the functional assessment of HIV Infection (FAHI) + Kaposi sarcoma (KS) questionnaire, in participants with KS, and explore changes in QOL of participants on treatment with sEphB4-HSA.

OUTLINE:
Patients receive sEphB4-HSA intravenously (IV) over 1 hour on days 1 and 15. Treatment repeats every 28 days for up to 12 cycles in the absence of further disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 1 month; patients with partial response or better are followed up every 3 months for up to 1 year.

Eligibility

1. Participants may be treatment naive, refractory to or intolerant of one or more prior therapies, or treated with prior systemic treatment including but not limited to liposomal doxorubicin
2. Participants must have biopsy-proven KS involving skin with or without visceral involvement
3. If HIV-positive, any cluster of differentiation (CD)4 count will be allowed on study
4. Eastern Cooperative Oncology Group (ECOG) performance status =< 2 or Karnofsky performance score (KPS) >= 50%
5. Life expectancy of greater than 3 months
6. Absolute neutrophil count >= 1,500/mcL* (within 21 days of enrollment) * Participants may be receiving growth factor support to meet these criteria
7. Platelets >= 100,000/mcL (within 21 days of enrollment)
8. Total bilirubin =< 1.5 x upper limit of normal (ULN) (within 21 days of enrollment)
9. Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN
10. 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 (within 21 days of enrollment)
11. 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
12. 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)
13. 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, 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
14. If participant is HIV positive, participants must be on a stable antiretroviral regimen for at least 12 weeks prior to study enrollment
15. 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
16. Participants must, in the opinion of the investigator, be capable of complying with the protocol