sEphB4-HSA in Treating Participants With BCG-Unresponsive or Refractory Bladder Cancer

Inclusion Criteria:

• Patients with bladder CIS, or completely resected high grade Ta/T1 lesions that areBCG unresponsive; unresponsive is BCG refractory and/or BCG relapsing
• BCG refractory: persistent high-grade disease at 6 months despite receiving atleast 5-6 induction instillations and at least one maintenance (two of threeinstillations) in a 6 month period
• BCG relapsing: recurrence of high-grade disease after achieving a disease-freestate at 6 months after receiving at least 5-6 induction instillations and atleast one maintenance (two of three instillations) in a 6 month period
• Eastern Cooperative Oncology Group performance status 0 to 2
• Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information
• NOTE: HIPAA authorization may be included in the informed consent or obtainedseparately
• Females must not be breastfeeding
• Patients must be willing to undergo additional radiologic imaging while on study
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcl
• Total bilirubin =< 1.5 X institutional upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
• Creatinine =< 1.5 X institutional upper limit of normal
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, forthe duration of study participation, and for 90 days following completion of therapy;should a woman become pregnant or suspect she is pregnant while participating in thisstudy, she should inform her treating physician immediately
• Female of child-bearing potential is any woman (regardless of sexual orientation,having undergone a tubal ligation, or remaining celibate by choice) who meets thefollowing criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
• Ability to understand and the willingness to sign a written informed consent
• Absence of concomitant upper tract urothelial carcinoma (i.e. cancer within the kidneyor ureter) as evidenced on computed tomography (CT) urogram and no visible lesionand/or biopsy proven evidence of urothelial carcinoma within the prostatic urethra (i.e. biopsy proven presence of cancer within the prostatic urethra)
• Patient has a desire to preserve organ, understanding the risks of delaying standardof care
• Patient is ineligible, declines, or is considered ineligible to undergo radicalcystectomy

Exclusion Criteria:

• If they are undergoing or have undergone in the past 4 weeks (28 days) any othertherapy for their cancer, including radiation therapy and chemotherapy
• If they have a major systemic infection requiring antibiotics 72 hours or less priorto the first dose of study drug
• If they have untreated central nervous system (CNS) metastasis; patients whose CNSmetastases have been treated by surgery or radiotherapy, who are no longer oncorticosteroids, and who are neurologically stable may be enrolled in the doseescalation portion of the trial
• If they have New York Heart Association (NYHA) class 3 or 4; myocardial infarction,acute coronary syndrome, 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-HSA orplaces the patient at undue risk for treatment related complications
• If they have any other condition, including mental illness or substance abuse, deemedby the investigator to be likely to interfere with a patient?s ability to signinformed consent, cooperate and participate in the study, or interferes with theinterpretation of the results
• If they are pregnant or lactating
• If they are on any dose of warfarin or are on full dose anticoagulation with otheragents, including low molecular weight heparin, antithrombin agents, anti-plateletagents and full dose aspirin within 7 days prior to first dose of study drug; patientson prophylactic doses of low-molecular weight heparin are allowed
• If they have had any active bleeding in the last =< 4 weeks or have an otherwise knownbleeding diathesis
• Patients may not be receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologiccomposition to agent(s) or other agents used in study
• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliance withstudy requirements
• Patients must not be pregnant or nursing due to the potential for congenitalabnormalities and the potential of this regimen to harm nursing infants
• Evidence of a history of a stroke or myocardial infarction within the last 6 monthsprior to study enrollment
• Previous intravesical immunotherapy less than 3 months before study entry; Note: if apatient is eligible for the study but has had intravesical immunotherapy within thepast 3 months, they can enroll in the study and initiation of treatment of the drugwill be delayed until a minimum of 90 days has passed since the previous treatment
• Renal and hepatic function values exceeding 2 times the upper normal value
• Patients who cannot hold instillation for 2 hours
• Patients who cannot tolerate intravesical dosing or intravesical surgical manipulation