A Study of sEphB4-HSA in Kaposi Sarcoma

NCT03993106 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 101
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 3

Brief Summary

sEphB-HSA may prevent tumor cells from multiplying and blocks several compounds that promote the growth of blood vessels that bring nutrients to the tumor. The purpose of this study is to learn if sEphB4-HSA will decrease the number or size of Kaposi sarcoma lesions in people.

Conditions

Kaposi Sarcoma

Outcome Measures

Primary Outcomes (1)

• Evaluate the change in clinical response and toxicity of sEphB4-HSA at 10 mg/kg every 2 weeks in participants with KS.

  The observed proportions of participants experiencing clinical response and unacceptable toxicity will be calculated with 95% confidence intervals. For clinical response, the Kaplan-Meier method will be used to estimate the distribution for time to death assessed for up to 1 month after treatment completion; for time to progression assessed from chemotherapy initiation to first documented progression up to 1 month after treatment completion; and for time to response assessed from the first dose until first documented response up to 1 month after completion of treatment. The Kaplan-Meier method will then be used to estimate the distribution of time to response, time to relapse, and time to death. Adverse events will be tabulated according to type and severity.

  Every 4 weeks until study completion (average 6 months).

Secondary Outcomes (10)

• Effects of sEphB4-HSA on tumor cell apoptosis and proliferation.

  Optional skin biopsies at study entry and any Day Cycle 3 (one cycle is 28 days).

• Effects of sEphB4-HSA on immune response as measured in blood

  Blood draws at baseline, Cycle 1 Days 1 & 15 (one cycle is 28 days) and Day 1 of Cycles 4, 7, 10 and at study completion (average of 6 months)

• Effects of sEphB4-HSA on immune response as measured in tissue

  Optional skin biopsies at study entry and any Day Cycle 3 (one cycle is 28 days).

• Effects of sEphB4-HSA on viral replication and gene expression of human herpes virus-8 (HHV-8).

  Baseline, Cycle 1, Day 1, Day 1 of every third cycle (one cycle is 28 days) thereafter and at study completion (average of 6 months).

• Changes in the VEGF-Notch-EphrinB2 angiogenic pathway

  At study entry and week 8-12 of study drug.

Study Arms (1)

Study Drug

EXPERIMENTAL

All study participants will receive sEphB4-HSA through a needle in a vein in their arm for an hour in an outpatient clinic. All study participants will receive two doses of study drug on Days 1 and 15 of each 4 week cycle.

Drug: sEphB4-HSA

Interventions

sEphB4-HSA DRUG

sEphB-HSA may prevent tumor cells from multiplying and blocks several compounds that promote the growth of blood vessels that bring nutrients to the tumor.

Study Drug

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vasgene Therapeutics, Inc: lead

Study Sites (3)

AIDS Healthcare Foundation

Beverly Hills, California, 90211, United States

RECRUITING

CAN (Community AIDS Network) Community Health

Sarasota, Florida, 34237, United States

RECRUITING

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

MeSH Terms

Conditions

Sarcoma, Kaposi

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue

Study Officials

• Carl Millner, M.D.

  AIDS Healthcare Foundation

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarah E. Cole, M.S.

CONTACT

626-840-7756; scoleemail@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2019
• First Posted: June 20, 2019
• Study Start: September 17, 2020
• Primary Completion: December 1, 2024
• Study Completion: June 1, 2025
• Last Updated: May 2, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)