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Advanced Malignant Solid NeoplasmPhase 1NCT01591356

EphA2 siRNA in Treating Patients With Advanced or Recurrent Solid Tumors

A Phase 1 study testing EphA2-targeting DOPC-encapsulated siRNA, Laboratory Biomarker Analysis and Pharmacological Study in people with Advanced Malignant Solid Neoplasm, run by M.D. Anderson Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Malignant Solid Neoplasm
What is being tested?
EphA2-targeting DOPC-encapsulated siRNA, Laboratory Biomarker Analysis and Pharmacological Study
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
49 participants
Where
1 siteUnited States
Study dates
1 Jul 2015to 30 Apr 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Prothrombin time (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 partial thromboplastin time (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 gonadotropin-releasing hormone [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 first dose of study drug (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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: EphA2 Gene Targeting Using Neutral Liposomal Small Interfering RNA Delivery: A Phase I Clinical Trial

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
EphA2-targeting DOPC-encapsulated siRNA, Laboratory Biomarker Analysis, Pharmacological Study

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EphA2-targeting DOPC-encapsulated siRNADrug

    Also called siRNA-EphA2-DOPC

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

Study groups in NCT01591356
Study groupRoleWhat they receive
Treatment (EphA2-targeting DOPC-encapsulated siRNA)ExperimentalPatients 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.
Receives: Drug: EphA2-targeting DOPC-encapsulated siRNA; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Up to 5 years

  2. 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.

    Measured: Up to 21 days

Secondary outcomes (6)

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

    Will be calculated along with 90% exact confidence intervals.

    Measured: Up to 5 years

  2. Changes in ephrin type-A receptor 2 expression

    Tissue effects will be assessed in core biopsy samples collected pre-treatment and course 1 day 2 or day 3 (timed with biomarker assessment).

    Measured: Baseline to up to day 4 of course 1

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

    Analysis will be performed for both between (dose-effect) and within (changes from baseline) patient cohorts.

    Measured: Up to 5 years

  4. Objective response

    The best response recorded from the start of the treatment until disease progression/recurrence

    Measured: Up to 5 years

  5. Duration of response

    measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

    Measured: Up to 5 years

  6. Time to treatment progression

    The duration of time from study entry to time of recurrence or death, whichever occurs first.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 May 2012 (estimated)
  2. Study start1 Jul 2015
  3. Primary completion30 Apr 2027 (estimated)
  4. Study completion30 Apr 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
49 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01591356
Sponsor's protocol ID
2011-0216
Other IDs
NCI-2015-00745, RP120214, NCI-2012-00755, 2011-0216, P50CA093459
Status last verified
Jul 2026
First submitted
2 May 2012
Last updated
21 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 28265009

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing EphA2-targeting DOPC-encapsulated siRNA, Laboratory Biomarker Analysis and Pharmacological Study in people with Advanced Malignant Solid Neoplasm, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 21 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Toxicity profile of ephrin type-A receptor 2-targeting 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine-encapsulated short-interfering ribonucleic acid (time frame: Up to 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01591356, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2026; AzTrials last refreshed its copy on 6 Nov 2026.

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