Gastric NeoplasmsPhase 1RIOT3NCT07001592
Intra-tumoral (IT) Injection of vvDD-hIL2-2-RG-1 for Metastatic Gastrointestinal and Peritoneal Tumors
A Phase 1 study testing vvDD-hIL-2-RG-1 in people with Gastric Neoplasms and Esophageal Cancer, run by Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute) at 1 site in United States.
Trial summary
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 interleukin 2), in patients with advanced abdominal cancer. The study will involve three dose levels, with three to six patients enrolled at each level. Read more about this study
- Who is it for?
- Ages 18 to 69 years
- Conditions the study is for
- Gastric Neoplasms, Esophageal Cancer, Liver Cancer
- What is being tested?
- vvDD-hIL-2-RG-1
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 6 May 2025to May 2028
- 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 to 69 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females age, 18 to < 70 years at the time of consent
- Histologically confirmed metastases from gastrointestinal tumors with molecular determinants for MSI and KRAS.
- For microsatellite stable (MSS) tumors, subjects must have failed (or be ineligible for) standard 1st and 2nd line chemotherapy. For microsatellite instability-high (MSI-H) tumors, subjects must also have failed (or be ineligible for) systemic immunotherapy.
- Karnofsky Performance Status (KPS) of > 70
- Anticipated survival of at least 12 weeks.
- Written informed consent in accordance with national, local, and institutional guidelines obtained prior to any study procedures (subject or subject's legally authorized representative (LAR) must have the ability to understand and willingness to sign a written informed consent).
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- Adequate bone marrow function: WBC > 2,000 and <50,000 cells/mm3, ANC > 1,000 cells/mm3, hemoglobin >8 g/dL, and platelet count >100,000 cells/mm3.
- Adequate renal function: serum creatinine level ≤ 2xULN
- Adequate liver function: Serum bilirubin < 1.5 x ULN
- Acceptable coagulation status: INR < ULN +15%. All patients must be able to suspend anticoagulant therapy for study specific biopsies and intra-tumoral injection.
- Women of childbearing potential (defined as all women physiologically capable of becoming pregnant) must have negative serum or urine pregnancy test.
- If sexually active, to prevent pregnancy and to prevent the spread of virus, subject must use an acceptable method of contraception as well as barrier contraception from screening through 6 weeks following study treatment with vvDD-hIL-2-RG-1.
- Subjects must be willing to comply with all study procedures, requirements, adhere to post-treatment care instructions and follow-up examinations.
- Have measurable disease based on RECIST 1.1 criteria.
- Have at least one tumor at least 1 cm in diameter amenable to safe intra-tumoral injection.
Who cannot join
- Pregnant or nursing an infant.
- Systemic corticosteroid or other immunosuppressive medication use within 2 weeks of the study treatment.
- Significant immunodeficiency (e.g. due to underlying illness and/or medication) in subject or household contacts (must be able to avoid household contact with immunodeficient person for 3 weeks).
- Clinically significant active infection or uncontrolled medical condition (e.g., pulmonary, neurological, cardiovascular, gastrointestinal, genitourinary) considered high risk for investigational new drug treatment, per investigator discretion.
- Active eczema or psoriasis or other inflammatory skin conditions
- Unstable cardiac disease which includes but is not limited to any of the following within 6 months prior to study entry: myocardial infarction (MI), unstable angina, congestive heart failure, myocarditis, ventricular arrhythmias diagnosed and requiring medication.
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- New York Heart Association functional class III-IV heart failure on active treatment
- Pulse oximetry of < 90% in room air at rest
- Subjects who have received radiation, chemotherapy or other potentially immunosuppressive therapy within 2 weeks prior to study screening and within 4 weeks prior to anticipated vvDD-hIL-2-RG-1 treatment.
- Experienced a severe systemic reaction or side-effect as a result of a previous smallpox vaccination.
- Subjects who, in the opinion of the Investigator, have a medical condition that would subject the subject to prohibitive risk by participation in this study, or who may be unable to safely complete the required tumor biopsies.
- Subjects with household contacts who are children < 5 years old, have active eczema, psoriasis or other inflammatory skin conditions or have a significant immunodeficiency due to underlying illness (e.g. human immunodeficiency virus) and/or medication (e.g. systemic corticosteroids) will be excluded unless alternate living arrangements can be made during the subject's active dosing period and for three weeks following the study medication.
- Vaccination with a live virus in the previous 60 days prior to Day 0.
- Inability or unwillingness to give informed consent.
- Is unable or unwilling to comply with protocol follow-up requirements. -
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
AHN West Penn Hospital
Pittsburgh, Pennsylvania, 15224
Patrick Wagner, MD, 412-359-3731, patrick.wagner@ahn.org
AHN Clinical Trial Contact, 412-359-3731, clinicaltrials@ahn.org
About this study
Official title: A Phase I Dose-Escalation Trial of vvDD-hIL2-2-RG-1 (Vaccina Virus Double Deleted) Administered by Intra-tumoral (IT) Injection for Metastatic Gastrointestinal and Peritoneal Tumors
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 interleukin 2), in patients with advanced abdominal cancer. The study will involve three dose levels, with three to six patients enrolled at each level.
vvDD-hIL2 is a genetically modified vaccinia virus, derived from the virus previously used for smallpox vaccination. The modification is intended to target and destroy tumors while minimizing harm to healthy tissues by stimulating the body's immune response.
Read more
Participants will receive an injection of vvDD-hIL2 directly into their abdominal tumors at AHN West Penn. The study team will monitor for side effects and assess tumor response to the treatment.
Active participation will last up to two months, involving seven clinic visits and approximately four lab visits at AHN West Penn Hospital. Visits will include standard of care procedures as well as study-specific tests and exams. Most visits will last one to two hours, with some extending to two to three hours. The drug administration day will require a twelve-hour visit.
Effectiveness and side effects will be evaluated through blood draws, oral swabs, urinalysis and tissue biopsies. Tissue samples will be used for genomic analysis and stored for potential future research. Data collected may also be used for future research purposes.
Previous human trials of vvDD-hIL2 have reported side effects such as pain, rash or inflammation at the injection site, low-grade fevers, flu-like symptoms, and fatigue. There is a rare risk of rash transmission to close contacts with skin openings, and information on limiting contact and managing rash development will be provided.
Read the detailed description
This is a Phase I, open-label, single dose, dose-escalation trial in subjects with metastatic gastrointestinal tumors who have failed standard systemic chemotherapy or immunotherapy. Gastrointestinal tumors include esophageal cancer (EC), gastric cancer (GC), colon cancer (CC), rectal cancer (RC), liver cancer (LC), and pancreatic cancer (PC)
The vvDD-IL-2 virus was designed to activate T-cells with a goal to reduce systemic toxicity while optimizing immune clearance of tumors following intraperitoneal delivery. Utilizing a platform of a thymidine kinase (tk) and vaccinia growth factor (vgf) deleted oncolytic Western Reserve (WR) strain vaccinia virus (vvDD), vvDD-IL-2 variants have been designed to deliver membrane bound IL-2 into the tumor microenvironment.
All subjects who have refractory tumors will receive the virus at one of the three dose levels in a single dose sequential dose modified toxicity probability interval (mTPI) design. Eligible subjects will receive one needle injection (per tumor) of vvDD-hIL-2-RG-1. A minimum of 28 days observation period must pass after injection of the first subject in each level without experiencing a dose-limiting toxicity (DLT) before administering/injecting the second patient at that dose level. A new dose level will not be initiated until the completion of the 28-day observation period from the administration of the previous dose level.
- Conditions
- Gastric Neoplasms, Esophageal Cancer, Liver Cancer, Liver Metastasis, MSS-CRC, MSS
- Being tested
- vvDD-hIL-2-RG-1
- Keywords
- Oncolytic virus, vaccinia, immunotherapy, intra-tumoral, intra-peritoneal
- Medical subject headings
- Stomach Neoplasms, Esophageal Neoplasms, Liver Neoplasms, Vaccinia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
vvDD-hIL-2-RG-1Biological
A single dose of the investigational agent will be injected intratumorally at one of the following three dose levels.
Level 1: 3 x 108 p.f.u. Level 2: 1 x 109 p.f.u. Level 3: 3 x 109 p.f.u. p.f.u = Plaque-forming unit(s)
Dose will be escalated in cohorts of 3, according to a standard 3+3 design.
| Study group | Role | What they receive |
|---|---|---|
| vvDD-hIL-2-RG-1 | Experimental | vvDD-hIL-2-RG-1 administered via intra-tumoral (IT) injection Receives: Biological: vvDD-hIL-2-RG-1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events (Safety) of vvDD-hIL-2-RG-1
Measured by frequency and severity of adverse events (AEs) at each dose level as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Measured: maximum 28 days
Maximally-tolerated dose (MTD) of vvDD-hIL-2-RG-1
Determined by measuring the number of AEs and DLTs at each dose level
Measured: maximum 28 days
Maximum-feasible dose (MFD) of vvDD-hIL-2-RG-1
Determined by measuring the number of AEs and DLTs at each dose level
Measured: maximum 28 days
Secondary outcomes (2)
Determine the replication rate of vvDD-hIL-2-RG-1 following IT injection
Measured by virus replication in biospecimens (blood, tumor tissue, oral swabs, urine samples and swabs of any skin lesions)
Measured: maximum 28 days
Determine changes in cytokine concentrations and immune cell populations in blood and tissue following vvDD-hIL-2-RG-1 injection using magnetic bead flow cytometry-based assays
Measured by examining concentrations of a panel cytokines and density of immune cell subpopulations in blood and tissue following vvDD-hIL-2-RG-1 injection
Measured: maximum 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2025
- Study start6 May 2025
- Primary completionApr 2028 (estimated)
- Study completionMay 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastric NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Patrick Wagner, MD, FACS, Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
- Investigators
- Patrick Wagner, MD, Principal investigator, Allegheny Health Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07001592
- Sponsor's protocol ID
- RIOT3 - vvDD-hIL2-2-RG-1
- Other IDs
- 2024-087
- Acronym
- RIOT3
- Status last verified
- May 2025
- First submitted
- 6 May 2025
- Last updated
- 3 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose-Escalation Trial of vvDD-hIL2-2-RG-1 (Vaccina Virus Double Deleted) Administered by Intra-tumoral (IT) Injection for Metastatic Gastrointestinal and Peritoneal Tumors
- ClinicalTrials.gov ID
- NCT07001592
- Acronym / sponsor ID
- RIOT3 / RIOT3 - vvDD-hIL2-2-RG-1
- Conditions
- Gastric Neoplasms, Esophageal Cancer, Liver Cancer, Liver Metastasis, MSS-CRC, MSS
- Keywords
- Oncolytic virus, vaccinia, immunotherapy, intra-tumoral, intra-peritoneal
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)University, hospital or other
- Study start
- 6 May 2025 (actual)
- Primary completion
- Apr 2028 (estimated)
- Study completion
- May 2028 (estimated)
- First posted
- 3 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 interleukin 2), in patients with advanced abdominal cancer. The study will involve three dose levels, with three to six patients enrolled at each level.
vvDD-hIL2 is a genetically modified vaccinia virus, derived from the virus previously used for smallpox vaccination. The modification is intended to target and destroy tumors while minimizing harm to healthy tissues by stimulating the body's immune response.
Participants will receive an injection of vvDD-hIL2 directly into their abdominal tumors at AHN West Penn. The study team will monitor for side effects and assess tumor response to the treatment.
Active participation will last up to two months, involving seven clinic visits and approximately four lab visits at AHN West Penn Hospital. Visits will include standard of care procedures as well as study-specific tests and exams. Most visits will last one to two hours, with some extending to two to three hours. The drug administration day will require a twelve-hour visit.
Effectiveness and side effects will be evaluated through blood draws, oral swabs, urinalysis and tissue biopsies. Tissue samples will be used for genomic analysis and stored for potential future research. Data collected may also be used for future research purposes.
Previous human trials of vvDD-hIL2 have reported side effects such as pain, rash or inflammation at the injection site, low-grade fevers, flu-like symptoms, and fatigue. There is a rare risk of rash transmission to close contacts with skin openings, and information on limiting contact and managing rash development will be provided.
Detailed description
This is a Phase I, open-label, single dose, dose-escalation trial in subjects with metastatic gastrointestinal tumors who have failed standard systemic chemotherapy or immunotherapy. Gastrointestinal tumors include esophageal cancer (EC), gastric cancer (GC), colon cancer (CC), rectal cancer (RC), liver cancer (LC), and pancreatic cancer (PC)
The vvDD-IL-2 virus was designed to activate T-cells with a goal to reduce systemic toxicity while optimizing immune clearance of tumors following intraperitoneal delivery. Utilizing a platform of a thymidine kinase (tk) and vaccinia growth factor (vgf) deleted oncolytic Western Reserve (WR) strain vaccinia virus (vvDD), vvDD-IL-2 variants have been designed to deliver membrane bound IL-2 into the tumor microenvironment.
All subjects who have refractory tumors will receive the virus at one of the three dose levels in a single dose sequential dose modified toxicity probability interval (mTPI) design. Eligible subjects will receive one needle injection (per tumor) of vvDD-hIL-2-RG-1. A minimum of 28 days observation period must pass after injection of the first subject in each level without experiencing a dose-limiting toxicity (DLT) before administering/injecting the second patient at that dose level. A new dose level will not be initiated until the completion of the 28-day observation period from the administration of the previous dose level.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| vvDD-hIL-2-RG-1 | Experimental | Biological: vvDD-hIL-2-RG-1vvDD-hIL-2-RG-1 administered via intra-tumoral (IT) injection |
Who may qualify
- Ages
- 18 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Males or females age, 18 to < 70 years at the time of consent
- Histologically confirmed metastases from gastrointestinal tumors with molecular determinants for MSI and KRAS.
- For microsatellite stable (MSS) tumors, subjects must have failed (or be ineligible for) standard 1st and 2nd line chemotherapy. For microsatellite instability-high (MSI-H) tumors, subjects must also have failed (or be ineligible for) systemic immunotherapy.
- Karnofsky Performance Status (KPS) of > 70
- Anticipated survival of at least 12 weeks.
Key exclusion criteria (15 listed)
- Pregnant or nursing an infant.
- Systemic corticosteroid or other immunosuppressive medication use within 2 weeks of the study treatment.
- Significant immunodeficiency (e.g. due to underlying illness and/or medication) in subject or household contacts (must be able to avoid household contact with immunodeficient person for 3 weeks).
- Clinically significant active infection or uncontrolled medical condition (e.g., pulmonary, neurological, cardiovascular, gastrointestinal, genitourinary) considered high risk for investigational new drug treatment, per investigator discretion.
- Active eczema or psoriasis or other inflammatory skin conditions
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| vvDD-hIL-2-RG-1A single dose of the investigational agent will be injected intratumorally at one of the following three dose levels. Level 1: 3 x 108 p.f.u. Level 2: 1 x 109 p.f.u. Level 3: 3 x 109 p.f.u. p.f.u = Plaque-forming unit(s) Dose will be escalated in cohorts of 3, according to a standard 3+3 design. | Biological | vvDD-hIL-2-RG-1 |
Primary outcome
Incidence of Treatment-Emergent Adverse Events (Safety) of vvDD-hIL-2-RG-1
Time frame: maximum 28 days
Measured by frequency and severity of adverse events (AEs) at each dose level as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Maximally-tolerated dose (MTD) of vvDD-hIL-2-RG-1
Time frame: maximum 28 days
Determined by measuring the number of AEs and DLTs at each dose level
Maximum-feasible dose (MFD) of vvDD-hIL-2-RG-1
Time frame: maximum 28 days
Determined by measuring the number of AEs and DLTs at each dose level
2 secondary outcomes
Determine the replication rate of vvDD-hIL-2-RG-1 following IT injection
Time frame: maximum 28 days
Determine changes in cytokine concentrations and immune cell populations in blood and tissue following vvDD-hIL-2-RG-1 injection using magnetic bead flow cytometry-based assays
Time frame: maximum 28 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Patrick Wagner, MD principal investigator
Allegheny Health Network
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing vvDD-hIL-2-RG-1 in people with Gastric Neoplasms and Esophageal Cancer, run by Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute) 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 15 inclusion and 15 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: looking for participants now, as of the sponsor's last update on 3 Jun 2025. 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?
Contact Patrick Wagner, MD (412-359-3731, patrick.wagner@ahn.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events (Safety) of vvDD-hIL-2-RG-1 (time frame: maximum 28 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Jun 2025.