EphA2 Gene Targeting Using Neutral Liposomal Small Interfering RNA Delivery
Verified November 2014 by M.D. Anderson Cancer Center
Ovarian Cancer Research Fund
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
First received: May 2, 2012
Last updated: November 7, 2014
Last verified: November 2014
The goal of this clinical research study is to learn about the safety of siRNA-EphA2-DOPC when given to patients with advanced, recurrent cancer. Researchers also want to learn the highest tolerable dose of this drug that can be given.
siRNA-EphA2-DOPC is designed to shut down the activity of a gene that causes tumor growth.
||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||EphA2 Gene Targeting Using Neutral Liposomal Small Interfering RNA Delivery (IND# 72924): A Phase I Clinical Trial
Primary Outcome Measures:
| Estimated Enrollment:
| Study Start Date:
| Estimated Primary Completion Date:
||March 2020 (Final data collection date for primary outcome measure)
siRNA-EphA2-DOPC administered by vein twice weekly on Days 1 and 4 of each week for 3 weeks. One cycle equals 3 weeks of treatment (21 day schedule). Treatment will normally be administered on an outpatient basis; however, inpatient administration may be relevant in some situations. siRNA-EphA2-DOPC administered over 30 (+/- 5 minutes). Starting dose level of siRNA-EphA2-DOPC 450 ug/m2 by vein twice weekly.
Starting dose: 450 ug/m2 by vein twice weekly on Days 1 and 4 of each 3 week cycle.
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- All patients with histologic proof of advanced solid tumors, who are not candidates for known regimens or protocol treatments of higher efficacy or priority.
- Subject/patient must be 18 years or older (no dosing or adverse event data are currently available on the use of EphA2 siRNA-DOPC in patients < 18 years of age).
- Eastern Cooperative Oncology Group (ECOG) performance status </=2.
- Clinical Laboratory Improvement Act (CLIA) certified Epha2 immunohistochemistry (IHC) evaluation. IHC staining will be performed on formalin fixed, paraffin-embedded tissue sections using a monoclonal EphA2 antibody. EphA2 expression will be assessed through a combination of the % of positive cells and the staining intensity. The % of positive cells will be rated as follows: 0 points, 0 to 5%; 2 points, 6 to 50%; 3 points, 50%. The staining intensity will be rated as follows: 1 point, weak intensity; 2 points, moderate intensity; 3 points, strong intensity. Points for expression and percentage of positive cells will be added, and an overall score will be assigned. Tumors will then be categorized into four groups: negative (overall score 0), 5% cells stained, regardless of intensity; weak expression (overall score 1), 1 to 2 points; moderate expression (overall score 2), 3 to 4 points; and strong expression (overall score 3), 5 to 6 points. An overall score of 3 will be defined as EphA2 overexpression in tumor cells.
- Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension. At least one lesion greater than 2 cm in short axis is required to ensure serial biopsy. When imaging (DCE-MRI, DW-MRI and PET-CT imaging) is being performed for Secondary Objectives (Dose Level III and during the Expansion Phase) at least one lesion (>/=2 cm) not adjacent to the diaphragm will be required when measured by conventional techniques, including palpation, plain x-ray, computed tomography (CT), and magnetic resonance imaging (MRI). A second lesion accessible for biopsy must also be present. Patients must have at least one 'target lesion' to be used to assess response on this protocol as defined by RECIST. This may be one of the lesions mentioned above. Tumors within a previously irradiated field will be designated as 'non-target' lesions.
- Resolution of any effects of prior therapy (except alopecia) to NCI CTCAE Version 4 grade </= 1 and to baseline laboratory values as defined in inclusion criteria 6.
- Patients must have adequate: Bone marrow function: HGB >/= 9 g/dL, WBC >/= 3,000/mcL, ANC >/= 1,500/mcL, PLT >/= 100,000/mcL; Hepatic function: Total bilirubin less than or equal to 1.5, SGOT and SGPT < 2.5 * institutional ULN; Renal function: Creatinine < 1.5 * ULN or creatinine clearance > 60ml/min according to Cockcroft-Gault formula; Neurologic function: Neuropathy (sensory and motor) </= to CTCAE grade 1; Blood coagulation parameters: PT such that international normalized ratio (INR) is < 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin or low molecular weight heparin) and a PTT < 1.2 times control.
- Patients should be free of active infection requiring intravenous antibiotics.
- Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration (study enrollment). Continuation of hormone replacement therapy is permitted. Stable regimens of hormonal therapy i.e. for prostate cancer (e.g. leuprolide, a GnRH agonist), ovarian or breast cancer are not exclusionary.
- Any other prior therapy directed at the malignant tumor, including immunologic agents, must be discontinued at least three weeks prior to registration (study enrollment) (6 weeks for nitrosoureas or mitomycin C).
- Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study and for at least 3 months after completion of EphA2 siRNA-DOPC therapy.
- Male subject agrees to use an acceptable method of contraception for the duration of the study.
- Patients must voluntarily sign an informed consent indicating that they are aware of the investigational nature of this study in keeping with the policies of the hospital.
- Patients may not be receiving any other investigational agents and/or other therapy for their cancer.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to DOPC, Magnevist, or FDG.
- Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as a known bleeding disorder, coagulopathy, or tumor involving major vessels.
- Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within 6 months of the first date of treatment on this study.
- Patients with clinically significant cardiovascular disease; this includes: Uncontrolled hypertension (greater than 140/90); Myocardial infarction or unstable angina within 6 months prior to registration; New York Heart Association (NYHA) Grade II or greater congestive heart failure; Serious cardiac arrhythmia requiring medication; Grade II or greater peripheral vascular disease; Patients with clinically significant peripheral artery disease, e.g., those with claudication, within 6 months of first date of treatment on this study.
- Patients whose circumstances do not permit completion of the study or the required follow-up.
- Patients who are pregnant or nursing. To date, no fetal studies in animals or humans have been performed with this agent.
- History of human immunodeficiency virus (HIV) or HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with EphA2 siRNA-DOPC.
- Patients whose tumor is not accessible for a core biopsy.
- Exclusion criteria (MRI specific): Patients who are ineligible to undergo an MRI scan for reasons such as claustrophobia or the presence of implanted devices or metallic foreign bodies that are not MR compatible. Patients with a known history of allergic reaction to gadolinium contrast agents. Patients with a history of a GFR of less than 60 or acute renal disease.
- Exclusion criteria (PET specific): Pregnant or nursing women. Extreme claustrophobia. Weight near or greater than 350 pounds.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01591356
|Contact: Robert Coleman, MD
|University of Texas MD Anderson Cancer Center
|Houston, Texas, United States, 77030 |
M.D. Anderson Cancer Center
Ovarian Cancer Research Fund
||Robert Coleman, MD
||M.D. Anderson Cancer Center
No publications provided
||M.D. Anderson Cancer Center
History of Changes
|Other Study ID Numbers:
|Study First Received:
||May 2, 2012
||November 7, 2014
||United States: Food and Drug Administration
Keywords provided by M.D. Anderson Cancer Center:
ClinicalTrials.gov processed this record on November 27, 2014
Advanced solid tumors