vvDD-hIL2 for Abdominal Cancer

(RIOT3 Trial)

Overseen By AHN Clinical Trial Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Pregnancy, Immunodeficiency, Cardiac disease, others

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

Compensation: Varies

Number of Visits: 7

Duration: 8 weeks

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called vvDD-hIL2, a specially modified virus designed to help the immune system attack abdominal cancer. The researchers aim to find the safest and most effective dose by injecting it directly into tumors. Participants should have advanced abdominal cancer and have previously tried standard treatments without success. The trial involves several clinic visits where doctors monitor side effects and assess tumor response. 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 innovative therapy.

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

The trial requires that you stop taking systemic corticosteroids or other immunosuppressive medications at least two weeks before the study treatment. If you're on anticoagulant therapy, you must be able to suspend it for study-specific procedures.

Is there any evidence suggesting that vvDD-hIL2 is likely to be safe for humans?

In earlier studies with people, the treatment vvDD-hIL2 caused some side effects, including pain, rash, or swelling at the injection site, mild fevers, flu-like symptoms, and tiredness. These side effects were usually mild and manageable. There is a rare chance that a rash could spread to others with open skin. Participants will receive advice on handling and preventing this. The treatment uses a genetically modified virus, similar to the one in smallpox vaccines, but it targets cancer cells. This design aims to fight cancer while remaining safe for healthy tissues. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for abdominal cancer, which often involve chemotherapy or surgery, vvDD-hIL2-2-RG-1 is unique because it uses a genetically engineered virus to deliver human interleukin-2 (hIL-2) directly into the tumor. This delivery method, known as intra-tumoral injection, allows for a more targeted approach, potentially minimizing damage to surrounding healthy tissues. Researchers are excited about vvDD-hIL2-2-RG-1 because it combines the virus's ability to selectively infect cancer cells with the immune-boosting properties of hIL-2, offering a novel way to enhance the body's natural defense against cancer.

What evidence suggests that vvDD-hIL2 might be an effective treatment for abdominal cancer?

Research shows that vvDD-hIL2, a modified virus, targets and destroys cancer cells while boosting the body's immune system to combat the tumor. Studies have demonstrated that this method enhances the body's tumor-fighting ability in mice and extends their lifespan. Additionally, combining this virus with other treatments has proven more effective than using a single treatment. Although these results are promising for some cancers, response rates can be low, and resistance to treatment remains a challenge. Researchers are still studying its effectiveness in humans, and this trial will specifically evaluate vvDD-hIL2 for its potential in fighting abdominal cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Patrick Wagner, MD

Principal Investigator

Allegheny Health Network

Are You a Good Fit for This Trial?

This trial is for patients with advanced abdominal cancers like esophageal, stomach, liver, peritoneal, and colorectal cancer. Participants must be able to travel to AHN West Penn for multiple visits. Those with immune system disorders or who have had recent vaccinations may not qualify.

Inclusion Criteria

I am mostly able to care for myself.

Anticipated survival of at least 12 weeks

I am capable of becoming pregnant and have a negative pregnancy test.

Exclusion Criteria

Medical condition that would subject the subject to prohibitive risk by participation in this study

Household contacts with specific conditions may lead to exclusion

Inability or unwillingness to give informed consent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of vvDD-hIL2-2-RG-1 via intra-tumoral injection, followed by monitoring for side effects and tumor response

8 weeks

7 clinic visits, 4 lab visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• vvDD-hIL2-2-RG-1

Trial Overview The study tests vvDD-hIL2-2-RG-1, a modified vaccinia virus aimed at destroying tumors by boosting the immune response. It involves direct tumor injections at increasing doses to find the safest and most effective level.

How Is the Trial Designed?

Group I: vvDD-hIL-2-RG-1 Experimental Treatment 1 Intervention

vvDD-hIL-2-RG-1 administered via intra-tumoral (IT) injection

Who Is Running the Clinical Trial?

Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)

Lead Sponsor

Trials

52

Recruited

13,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07001592

NCT07001592 | Intra-tumoral (IT) Injection of vvDD-hIL2-2- ... The modification is intended to target and destroy tumors while minimizing harm to healthy tissues by stimulating the body's immune response.

2. withpower.com withpower.com/trial/phase-1-esophageal-neoplasms-4-2025-4050c

vvDD-hIL2 for Abdominal Cancer (RIOT3 Trial) This research study aims to evaluate the safety and determine the optimal dose of a new experimental drug, vvDD-hIL2 (vaccinia virus double-deleted human ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12133479/

Advances of oncolytic vaccinia viruses armed with ... These results suggested that vvDD-IL-2-RG enhanced anti-tumor immunity and improved survival in mice (62). IL-2 combined with cisplatin is effective in treating ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1359610125001406

Role of Cytokine-based Immunotherapy Approaches in ... Despite encouraging results in select GI cancers, response rate is low, and treatment resistance poses a challenge in clinical practice.

5. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1272351/full

Recent progress in combination therapy of oncolytic ... Combining oncolytic VV therapy with other conventional cancer treatments has been shown to be synergistic and more effective than monotherapies.

6. go.drugbank.com go.drugbank.com/conditions/DBCOND0028483

Gastric Cancer (DBCOND0028483) A taxoid chemotherapeutic agent used as first-line and subsequent therapy for the treatment of advanced carcinoma of the ovary, and other various cancers ...