This pilot clinical trial studies the side effects of recombinant EphB4-HSA fusion protein before surgery in treating patients with transitional cell carcinoma of the bladder, prostate cancer, or kidney cancer. Recombinant EphB4-HSA fusion protein may block an enzyme needed for tumor cells to multiply and may also prevent the growth of new blood vessels that bring nutrients to the tumor. Giving recombinant EphB4-HSA fusion protein before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
PRIMARY OBJECTIVES: I. To determine the feasibility of, and adverse events associated with, treatment with soluble ephrin type-B receptor 4 (sEphB4)-human serum albumin (HSA) (recombinant EphB4-HSA fusion protein) prior to minimally invasive robotic surgery in patients with either muscle-invasive transitional cell carcinoma of the bladder; clear cell renal cell carcinoma (4 cm or greater); or prostate cancer Gleason (7 or under). SECONDARY OBJECTIVES: I. To determine tumor response to neoadjuvant sEphB4 as measured by imaging response and pathologic response. TERTIARY OBJECTIVES: I. To evaluate the expression of ephrin type-B receptor 4 (EphB4) and eph-related receptor tyrosine kinase ligand 5 (EphrinB2) in the archival tumor samples and explore potential associations with outcome. II. To bank specimens for future correlative biomarker studies based on the results of ongoing biomarkers analyses in the phase I of sEphB4-HSA as a single agent. III. To evaluate changes in deoxyribonucleic acid (DNA) methylation of the surgical specimen after being treated with sEphB4-HSA. IV. To evaluate the infiltration of immune cells into the tumor due to administering sEphB4-HSA. V. To evaluate the impact sEphB4-HSA has on vessel density on the tumor tissue. VI. To assess the applicability of using sEphB4-HSA for treating genitourinary cancers. VII. To assess the applicability of using contrast-enhanced ultrasound imaging for determining pathological complete response (pCR) rate. OUTLINE: Patients receive recombinant EphB4-HSA fusion protein intravenously (IV) over 60 minutes once weekly for 3 weeks (3 doses) in the absence of disease progression or unacceptable toxicity. Patients who agree may receive the fourth dose after an additional week as determined by the study medical oncologist. Two to four weeks after the last dose of recombinant EphB4-HSA fusion protein, patients undergo robotic-assisted radical cystectomy or robotic-assisted radical or partial nephrectomy. After completion of study treatment, patients are followed up for 30 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
2
Correlative studies
Correlative studies
Undergo robotic-assisted radical cystectomy
Given IV
Undergo robotic-assisted radical or partial nephrectomy
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
Feasibility, defined as the percentage of patients completing at least 3 doses of drug therapy without dose limiting toxicities (DLTs) and who are able to undergo minimally-invasive surgery as planned
Feasibility is defined for the purpose of this study as \>= 90% of patients completing at least 3 doses of drug therapy without DLTs and are able to undergo minimally-invasive surgery as planned.
Time frame: Up to 30 days after the last dose of sEphB4-HSA
Incidence of adverse events graded according to CTCAE version 4 or the Clavien-Dindo classification
All observed adverse events and complications will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity, and time of onset. Tables will be created to summarize these adverse events and complications, overall, by disease cohort, and by phase (neoadjuvant, during surgery, within 30 days post-operative, and days 31-90 post-operative).
Time frame: Up to 90 days post-surgery
Complete pathologic response defined as no residual evidence of invasive disease at the time of cystectomy or nephrectomy
Pathologic response rates will be calculated and 90% confidence intervals will be constructed.
Time frame: At the time of surgery
Radiologic response as evaluated by Response Evaluation Criteria in Solid Tumors version 1.1
Radiologic response rates will be calculated and 90% confidence intervals will be constructed.
Time frame: Up to 30 days post-surgery
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