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
Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
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. 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.
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)…
Eligibility
- Age range
- 18–69 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Males or females age, 18 to \< 70 years at the time of consent 2. Histologically confirmed metastases from gastrointestinal tumors with molecular determinants for MSI and KRAS. 3. 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. 4. Karnofsky Performance Status (KPS) of \> 70 5. Anticipated survival of at least 12 weeks. 6. Written informed consent in accordance wi…
Interventions
- BiologicalvvDD-hIL-2-RG-1
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.
Location
- AHN West Penn HospitalPittsburgh, Pennsylvania