Source: https://www.mycancergenome.org/content/clinical_trials/NCT01591356/
Timestamp: 2019-08-18 19:38:02
Document Index: 524127365

Matched Legal Cases: ['art 1', 'art 2', 'art 1', 'art 2', 'art 1', 'art 2']

Clinical Trial: NCT01591356 - My Cancer Genome
https://clinicaltrials.gov/show/NCT01591356
Brief Title:EphA2 Gene Targeting Using Neutral Liposomal Small Interfering RNA Delivery
Official Title:EphA2 Gene Targeting Using Neutral Liposomal Small Interfering RNA Delivery (IND# 72924): A Phase I Clinical Trial
ORG STUDY ID: 2011-0216
SECONDARY ID: NCI-2012-00755
SECONDARY ID: RP120214
NCT ID: NCT01591356
siRNA-EphA2-DOPC siRNA-EphA2-DOPC
You will be given standard drugs (hydrocortisone and diphenhydramine) to help decrease the risk of side effects. You may ask the study staff for information about how the drugs are given and their risks.
- Any updates to your medical history will be recorded, including any drugs you may be taking and any side effects you may be having.
- Blood (about 4-6 teaspoons) will be drawn for routine tests. If you are able to become pregnant, this blood and/or urine will be used for a pregnancy test.
- Blood (about 2 teaspoons each time) will be drawn for pharmacokinetic (PK) testing before the study drug dose, 1 time during the dose, at the end of the dose, and 6 times during the 6 hours after the dose. PK testing measures the amount of study drug in the body at different time points.
- Blood (about 3 tablespoons) will be drawn for biomarker testing.
- If you are in the third dose level in Part 1 of if you are in Part 2, you will have a dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) scan, a diffusion weighted imaging MRI (DWI-MRI) scan, and a fluorodeoxyglucose positron emission tomography (FDG-PET) scan to check if the study drug may be able to affect the tumor.
- You will have a core biopsy at the same site(s) that may have been tested at screening to check the status of the disease. This sample will be compared to the sample collected at screening.
- If you are in the third dose level in Part 1 of if you are in Part 2, you will have an FDG-PET scan, DCE-MRI scan, and a DWI-MRI to check the status of the disease and to learn how the drug may be affecting the tumor.
- Blood (about 2 teaspoons each time) will be drawn for PK testing before and at the end of the study drug dose.
- Blood (about 2 teaspoons each time) will be drawn for routine tests.
- Blood (about 2 teaspoons will be drawn for routine tests.
Before Cycle 2, if you are in the third dose level in Part 1 of if you are in Part 2, you will have an FDG-PET scan, DCE-MRI scan, and a DWI-MRI to check the status of the disease and to learn how the drug may be affecting the tumor.
- You will have a physical exam, including measurement of your vital signs, and weight.
- You will be asked about any drugs you may be taking and about any side effects you may be having.
- If you are able to become pregnant, blood (about 2 teaspoons) and/or urine will be collected for a pregnancy test.
- In Cycle 3 only, blood (about 4 teaspoons) will be drawn for biomarker testing.
- You will have a CT scan or x-ray to check the status of the disease.
- Blood (about 4-6 teaspoons) will be drawn for routine tests.
- Blood (about 4 teaspoons) will be drawn for biomarker testing.
- You will have a CT scan, MRI scan, or x-ray to check the status of the disease.
siRNA-EphA2-DOPC Experimental 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.
1. All patients with histologic proof of advanced solid tumors, who are not candidates for known regimens or protocol treatments of higher efficacy or priority.
2. 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).
3. ECOG performance status </=2.
4. All patients (dose escalation and dose expansion phases) must be willing to undergo pre- and post-treatment biopsies.
5. For the dose escalation phase, the trial population will be limited to solid tumor types
6. For dose expansion phase: patients must have EphA2 overexpression overall H-score of 3 or above in IHC evaluation.CLIA certified EphA2 IHC staining to be performed on formalin fixed, paraffin-embedded tissue sections using monoclonal EphA2 antibody. EphA2 expression to be assessed through a combo of % of positive cells and staining intensity. The % of positive cells will be rated: 0 points (pts), 0 to 5%; 2 pts, 6 to 50%; 3 pts, 50%. The staining intensity will be rated as follows: 1 pt, weak intensity; 2 pts, moderate intensity; 3 pts, strong intensity. Pts for expression and % of positive cells will be added; an overall score will be assigned. Tumors to be categorized into 4 groups: negative (overall score 0), 5% cells stained, regardless of intensity; weak expression (overall score 1), 1 - 2 pts; moderate expression (overall score 2), 3 - 4 pts; and strong expression (overall score 3), 5 - 6 pts. Overall H-score of 3 or above will be defined as EphA2 overexpression in tumor cells.
7. 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, CT, and 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.
8. Resolution of any effects of prior therapy (except alopecia) to NCI CTCAE Version 4.03 grade </= 1 and to baseline laboratory values as defined in inclusion criteria 7.
9. 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 X institutional ULN; Renal function: Creatinine < 1.5 x 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.
10. Patients should be free of active infection requiring intravenous antibiotics.
11. 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.
12. 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).
13. 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.
14. Male subject agrees to use an acceptable method of contraception for the duration of the study.
15. 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.
1. Patients may not be receiving any other investigational agents and/or other therapy for their cancer.
2. History of allergic reactions attributed to compounds of similar chemical or biologic composition to DOPC, Magnevist, or FDG.
3. 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.
4. Patients with history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases.
5. Patients with 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.
6. 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.
7. Patients whose circumstances do not permit completion of the study or the required follow-up.
8. Patients who are pregnant or nursing. To date, no fetal studies in animals or humans have been performed with this agent.
9. History of HIV or HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with EphA2 siRNA-DOPC.
10. Patients whose tumor is not accessible for a core biopsy.
11. 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.
12. Exclusion criteria (PET specific): Pregnant or nursing women. Extreme claustrophobia. Weight near or greater than 350 pounds.
Measure: Toxicity Profile of siRNA-EphA2
Description: Dose-limiting toxicity (DLT) defined as any event during the first cycle of study treatment that is considered possibly, probably or definitely related to study drug: Hematologic toxicity or Non-hematologic toxicity.