EphA2 siRNA for Cancer

Overseen By Shannon Westin, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Investigational agents

Disqualifiers: CNS disease, Cardiovascular disease, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 21 days per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with advanced solid tumors that have spread or returned after treatment. The goal is to determine the optimal dose and understand the side effects of EphA2 siRNA, a gene-targeting therapy designed to slow tumor growth by targeting a specific gene. This treatment may suit those who have tried other treatments without success and have tumors that are not easily treatable. Participants must have at least one tumor that can be measured and biopsied. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I have to stop taking my current medications for the trial?

The trial requires that any hormonal therapy directed at the malignant tumor be stopped at least one week before joining the study, but hormone replacement therapy and stable hormonal therapy for prostate, ovarian, or breast cancer can continue. Other cancer treatments must be stopped at least three weeks before the first dose of the study drug.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that EPHARNA, a treatment targeting a gene linked to tumor growth, has been promising in lab studies by reducing the activity of this gene. Early safety tests in animals indicated that the treatment was generally well-tolerated, with no major side effects.

As a phase 1 trial, the main goal is to determine the best dose and identify any side effects in humans. While lab studies provide some evidence, the treatment remains in the early stages of human testing. The full range of possible side effects in humans is not yet known. However, reaching this stage suggests it has shown enough potential for human trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard cancer treatments that often involve chemotherapy or radiation, the EphA2-targeting DOPC-encapsulated siRNA offers a unique approach. This treatment uses small interfering RNA (siRNA) to specifically target the EphA2 protein, which is commonly overexpressed in certain cancers. By encapsulating the siRNA in DOPC nanoparticles, it allows for more precise delivery to cancer cells, potentially minimizing harm to healthy tissues. Researchers are excited because this targeted mechanism could lead to fewer side effects and improved effectiveness in halting cancer progression.

What evidence suggests that EphA2-targeting DOPC-encapsulated siRNA might be an effective treatment for advanced or recurrent solid tumors?

Research has shown that a new treatment, which participants in this trial will receive, can slow tumor growth by targeting a specific gene called EphA2. This treatment uses tiny particles to deliver a substance that deactivates the EphA2 gene, known to aid tumor growth. In earlier studies, this method successfully reduced EphA2 gene activity in tumors just 48 hours after a single dose. Additionally, research indicates that targeting EphA2 can hinder cancer cells from adhering to nearby tissues, potentially preventing tumor spread. These early results suggest that this approach could be promising for treating advanced or recurring solid tumors. ^{1 3 6 7 8}

Who Is on the Research Team?

Shannon Westin, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced or recurrent solid tumors. Participants must have a performance status indicating they can carry out some activity and care for themselves, be willing to undergo biopsies, and not be on other cancer treatments. They should have measurable disease, acceptable organ function tests, no active infections requiring IV antibiotics, and agree to use birth control. Those with certain cardiovascular diseases, bleeding risks, severe allergies to similar drugs or components used in the study are excluded.

Inclusion Criteria

I agree to use contraception throughout the study.

I do not have an infection that needs IV antibiotics.

I am a woman who is post-menopausal, surgically sterilized, or will use birth control during and 3 months after the study.

Exclusion Criteria

Patients who are pregnant or nursing

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

I have a history or signs of brain or spinal cord disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive EphA2-targeting DOPC-encapsulated siRNA intravenously over 120 minutes on days 1 and 4, with cycles repeating every 21 days

21 days per cycle

2 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• EphA2-targeting DOPC-encapsulated siRNA

Trial Overview The trial is testing EphA2 siRNA encapsulated in DOPC liposomes which might inhibit tumor growth by targeting a gene linked to cancer progression. It's a phase I study aiming to determine the safest dose while observing how well patients tolerate it and its effect on their tumors through biomarker analysis.

How Is the Trial Designed?

Group I: Treatment (EphA2-targeting DOPC-encapsulated siRNA) Experimental Treatment 3 Interventions

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.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Gateway for Cancer Research

Collaborator

Trials

47

Recruited

2,500+

Institutional Funding for Federally Supported Clinical Trials (IFSCT)

Collaborator

Trials

1

Recruited

50+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01591356

Study Details | NCT01591356 | EphA2 siRNA in Treating ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7433191/

Targeting EphA2 in cancer - PMC - PubMed Central - NIH The immediate biological consequences of EphA2 phosphorylation include decreased cell–extracellular matrix (ECM) attachment. Ephrin A1- ...

3. aacrjournals.org aacrjournals.org/cancerres/article/65/15/6910/518373/Therapeutic-EphA2-Gene-Targeting-In-vivo-Using

Therapeutic EphA2 Gene Targeting In vivo Using Neutral ... DOPC-encapsulated siRNA targeting the oncoprotein EphA2 was highly effective in reducing in vivo EphA2 expression 48 hours after a single dose.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8309123/

Clinical Advances of siRNA-Based Nanotherapeutics for ... This review mainly focuses on the progress of siRNAs-loaded nanoparticles that have undergone clinical trials for cancer treatment.

5. withpower.com withpower.com/trial/phase-1-6-2015-83cb8

EphA2 siRNA for Cancer · Info for Participants 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 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28265009/

Preclinical Mammalian Safety Studies of EPHARNA ... - PubMed We developed 1,2-Dioleoyl-sn-Glycero-3-Phosphatidylcholine (DOPC) nanoliposomal EphA2-targeted therapeutic (EPHARNA). Here, we performed safety studies of ...

7. jhoonline.biomedcentral.com jhoonline.biomedcentral.com/articles/10.1186/s13045-020-00944-9

Targeting EphA2 in cancer - Journal of Hematology & Oncology The present manuscript reviewed the clinical associations and biological and cellular consequences of EphA2 overexpression in cancer.

8. asco.org asco.org/abstracts-presentations/ABSTRACT496098

EphA2 siRNA in DOPC nanoliposomes (EPHARNA) Background: EphA2 overexpression is common in human cancers and has an important role in promoting tumor growth and metastasis. Further, EphA2 has ...