A Study of GL-ONC1, an Oncolytic Vaccinia Virus, in Patients With Advanced Peritoneal Carcinomatosis
The purpose of this study is to determine whether GL-ONC1, an attenuated vaccinia virus, is safe when administered to patients with peritoneal carcinomatosis via an infusion within the abdominal cavity through an implanted catheter. The study seeks also to arrive at a recommended dose and schedule for future investigations, evidence of anti-tumor activity, detection of virus in body fluids, analysis of viral delivery to tumor and normal cells, and to evaluate if there is an antibody response to vaccinia virus.
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of Intraperitoneal Administration of GL-ONC1, a Genetically Modified Vaccinia Virus, in Patients With Peritoneal Carcinomatosis|
- Determine safety of administering GL-ONC1 intraperitoneally by the evaluation of the number of patients experiencing Adverse Events (type, frequency, and severity) [ Time Frame: Change from baseline over 24 hours, on days 2, 3, 4,5,6, 7 post treatment (Cycle 1) and change from baseline for Cycles 2- 4 CX/Days 1, 2, 3, 5, 8 post-treatment. Each cycle is 4 weeks and treatment will occur for a total of 4 cycles. ] [ Designated as safety issue: Yes ]The safety of GL-ONC1 will be assessed by the evaluation of the type, frequency, and severity of adverse events (AEs), changes in laboratory tests (haematological, chemistry, urinary), immunogenicity and physical examination
- Dose Level and Dose Schedule [ Time Frame: End of Phase I (at 18 mo.), at monthly treatments, and after study completion (expected at 36 mo.) ] [ Designated as safety issue: Yes ]Determination of recommended dose and schedule for phase II portion of trial and future investigations by analysis of safety and efficacy data
- Detection of Anti-tumor Activity [ Time Frame: Tumor imaging [pre-study, mid-term (Day 43), after last treatment (Day 106), for 1 year @ 12-week intervals for patients with stable disease/better); Tumor markers and peritoneal cytologies collected on average over 4 months ] [ Designated as safety issue: No ]Sampling of evidence of anti-tumor activity via standard imaging practices, viral delivery to tumor and normal cells, and immune response activity.
|Study Start Date:||February 2012|
|Estimated Study Completion Date:||November 2014|
|Estimated Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
Peritoneal carcinomatosis includes a variety of tumors with extensive metastasis throughout the peritoneal cavity (inside surface of the abdomen) and can be found with gall bladder, liver, colon, appendix, ovarian, pancreas, mesothelioma, pseudomyxoma peritonei, rectal, small bowel and stomach cancers. It broadly includes multiple tumors that develop in and line the peritoneal abdominal cavity and linings. These tumors may be difficult to completely remove surgically and may recur despite conventional systemic chemotherapy, thereby resulting in poor patient outcomes. In preclinical studies, GL-ONC1, an oncolytic vaccinia virus, has shown the ability to preferentially locate, colonize and destroy tumor cells in more than 30 different human tumors. A Phase I clinical study focusing on the safety and tolerability of GL-ONC1 intravenously administered to patients with a variety of solid tumor entities has shown that GL-ONC1 is well-tolerated at therapeutic dose levels, with documented evidence of antitumor activity. This additional Phase I/II study seeks to evaluate GL-ONC1 administered repetitively every 4 weeks up to 4 cycles via infusion using an implanted catheter in the peritoneal cavity. In Phase I, patients will be individually assessed for safety and dose limiting toxicity. The study aims of Phase II portion are continued collection of safety information to better define the tolerability of GL-ONC1, as well as viral replication and the action or effect of GL-ONC1 in humans at the selected dose level and dosing schedule for future trials. Throughout both phases of the study, anti-tumor effects will be evaluated.
|Contact: Ulrich M. Lauer, Prof.Dr.med.||+49 (0) 7071 298 email@example.com|
|University Hospital Tuebingen||Recruiting|
|Tuebingen, Germany, D-72076|
|Principal Investigator:||Ulrich M. Lauer, Prof. Dr. med.||University Hospital Tuebingen|
|Principal Investigator:||Michael Bitzer, Prof.Dr.med.||University Hospital Tuebingen|