This phase I trial studies the side effects and best dose of EphA2 siRNA in treating patients
with solid tumors that have spread to other places in the body and usually cannot be cured or
controlled with treatment (advanced) or have come back after a period of improvement
(recurrent). EphA2-targeting DOPC-encapsulated siRNA may slow the growth of tumor cells by
shutting down the activity of a gene that causes tumor growth.
I. To determine the safety and tolerability (toxicity profile) of EphA2-targeting
DOPC-encapsulated siRNA (EphA2 siRNA) delivered via neutral liposome
(1,2-dioleoyl-sn-glycero-3-phosphatidylcholine or DOPC) administered intravenously in
patients with advanced/recurrent malignancies.
II. To determine the maximal tolerated dose (MTD) or maximal administered dose (MAD) using a
modified toxicity probability interval (mTPI) design.
I. To determine efficacy (EphA2 expression modulation) at the MTD or MAD. II. To evaluate the
effect of EphA2 siRNA-DOPC on tumor and endothelial cell apoptosis.
III. To record the clinical activity (objective response, duration of response, and time to
treatment progression) of intravenous (IV) EphA2 siRNA -DOPC.
IV. To describe the symptom burden of patients receiving siRNA-EphA2-DOPC treatment.
I. To determine the pharmacokinetic profile of siRNA-EphA2-DOPC in blood. II. To determine
the effect of EphA2 siRNA-DOPC on tumor perfusion, apparent diffusion, and metabolism by
radiographic imaging (dynamic contrast-enhanced-magnetic resonance imaging [DCE-MRI],
diffusion weighted [DW]-MRI and fludeoxyglucose F-18-positron emission tomography
III. To determine the impact of EphA2 siRNA-DOPC on surrogate biomarkers in blood (cell-free
deoxyribonucleic acid [DNA], plasma/serum markers [vascular endothelial growth factor (VEGF),
caveolin 1 (CAV1), soluble EphrinA1], and exosomes).
OUTLINE: This is a dose-escalation study.
Patients receive EphA2-targeting DOPC-encapsulated siRNA IV over 120 minutes on days 1 and 4.
Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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