EphA2 siRNA in Treating Patients With Advanced or Recurrent Solid Tumors

NCT01591356 | Active Not Recruiting Phase 1 FDA Drug

• 5 other identifiers: 2011-0216NCI-2015-00745RP120214NCI-2012-00755P50CA093459
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (2)

• Toxicity profile of ephrin type-A receptor 2-targeting 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine-encapsulated short-interfering ribonucleic acid

  Will be graded according to Common Terminology Criteria for Adverse Events version 4.0

  Up to 5 years

• Maximal tolerated dose or maximal administered dose

  Will be defined as the dose level with the smallest difference among all tried doses. Will be determined using modified toxicity probability interval design.

  Up to 21 days

Secondary Outcomes (6)

• Percent of patients with ephrin type-A receptor 2 expression modulation, defined as a 50% decrease from baseline expression

  Up to 5 years

• Changes in ephrin type-A receptor 2 expression

  Baseline to up to day 4 of course 1

• Changes in endothelial and tumor cell apoptosis conducted by terminal deoxynucleotidyl transferase dUTP nick end labeling assay

  Up to 5 years

• Objective response

  Up to 5 years

• Duration of response

  Up to 5 years

Study Arms (1)

Treatment (EphA2-targeting DOPC-encapsulated siRNA)

EXPERIMENTAL

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.

Drug: EphA2-targeting DOPC-encapsulated siRNA; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (EphA2-targeting DOPC-encapsulated siRNA)

Pharmacological Study OTHER

Correlative studies

Treatment (EphA2-targeting DOPC-encapsulated siRNA)

EphA2-targeting DOPC-encapsulated siRNA DRUG

Given IV

Also known as: siRNA-EphA2-DOPC

Treatment (EphA2-targeting DOPC-encapsulated siRNA)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients with histologic proof of advanced solid tumors, who are not candidates for known regimens or protocol treatments of higher efficacy or priority
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• All patients (dose escalation and dose expansion phases) must be willing to undergo pre- and post-treatment biopsies
• For the dose escalation phase, the trial population will be limited to solid tumor types
• For dose expansion phase: patients must have EphA2 overexpression overall H-score of 3 or above in immunohistochemistry (IHC) evaluation; Clinical Laboratory Improvement Amendments (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
• Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension; at least one biopsiable lesion must be available; when imaging (DCE-MRI, DW-MRI and PET-computed tomography \[CT\] imaging) is being performed for secondary objectives (dose level III \[or when the dose reaches at least 1,500 ug/m\^2\] 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 Response Evaluation Criteria in Solid Tumors (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 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 grade =\< 1 and to baseline laboratory values as defined below
• Hemoglobin (HGB) \>= 9 g/dL
• White blood cells (WBC) \>= 3,000/mcL
• Absolute neutrophil count (ANC) \>= 1,500/mcL
• Platelet (PLT) \>= 100,000/mcL
• Total bilirubin less than or equal to 1.5
• Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) \< 2.5 x institutional upper limit of normal (ULN)
• Creatinine \< 1.5 x ULN or creatinine clearance \> 60 ml/min according to Cockcroft-Gault formula
• Neuropathy (sensory and motor) =\< to CTCAE grade 1

You may not qualify if:

• 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 fluorodeoxyglucose (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
• 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
• 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
• History of human immunodeficiency virus (HIV) or HIV-positive patients on combination antiretroviral therapy are ineligible
• Patients whose tumor is not accessible for a core biopsy
• 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 magnetic resonance (MR) compatible; patients with a known history of allergic reaction to gadolinium contrast agents; patients with a history of a glomerular filtration rate (GFR) of less than 60 or acute renal disease
• Pregnant or nursing women; extreme claustrophobia; weight near or greater than 350 pounds

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Gateway for Cancer Research: collaborator
• Institutional Funding for Federally Supported Clinical Trials (IFSCT): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Wagner MJ, Mitra R, McArthur MJ, Baze W, Barnhart K, Wu SY, Rodriguez-Aguayo C, Zhang X, Coleman RL, Lopez-Berestein G, Sood AK. Preclinical Mammalian Safety Studies of EPHARNA (DOPC Nanoliposomal EphA2-Targeted siRNA). Mol Cancer Ther. 2017 Jun;16(6):1114-1123. doi: 10.1158/1535-7163.MCT-16-0541. Epub 2017 Mar 6.

  PMID: 28265009 DERIVED

Related Links

• MD Anderson Cancer Center

Study Officials

• Shannon Westin

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2012
• First Posted: May 4, 2012
• Study Start: July 1, 2015
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2027
• Last Updated: January 7, 2026

Record last verified: 2026-01

Locations

US (1)