Ignite Creation Date:
2025-12-24 @ 11:29 PM
Ignite Modification Date:
2025-12-25 @ 9:16 PM
Study NCT ID:
NCT01591356
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-07-28
First Post:
2012-05-02
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
EphA2 siRNA in Treating Patients With Advanced or Recurrent Solid Tumors
Sponsor:
M.D. Anderson Cancer Center
Organization:
Study Overview
Official Title:
EphA2 Gene Targeting Using Neutral Liposomal Small Interfering RNA Delivery: A Phase I Clinical Trial
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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.
Detailed Description:
PRIMARY OBJECTIVES:
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.
SECONDARY OBJECTIVES:
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.
EXPLORATORY OBJECTIVES:
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 \[18FDG-PET\]).
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.
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.
SECONDARY OBJECTIVES:
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.
EXPLORATORY OBJECTIVES:
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 \[18FDG-PET\]).
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.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: