IL-2 Expressing, Attenuated Salmonella Typhimurium in Unresectable Hepatic Spread
The working hypothesis is that oral administration of an attenuated strain of Salmonella typhimurium is safe and efficacious for patients with unresectable hepatic metastasis from a solid tumor cancer. The primary objective of the study is to determine the MTD of Samonella typhimurium in the treatment.
Cancer of the Liver
Biological: Salmonella typhimurium
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1 Study of an IL-2 Expressing, Attenuated Salmonella Typhimurium in Patients With Unresectable Hepatic Spread From Any Non-Hematologic Primary|
- Maximum Tolerated Dose (MTD) of Samonella typhimurium [ Time Frame: Up to 24 Weeks After Dose of Samonella typhimurium ] [ Designated as safety issue: Yes ]Maximum tolerated dose will be determined by the number of patients with Dose limiting toxicity (DLT) at a given dose level. DLT is defined as treatment related: Sepsis (salmonella) syndrome, Grade 4 vomiting or diarrhea, Other grade 3 or greater toxicity. If > or = 2 patients at a dose level has a DLT, this level will be declared the MTD.
- Efficacy of Salmonella typhimurium in Treating Unresectable Hepatic Metastases [ Time Frame: 8 Weeks After Treatment with Salmonella typhir ] [ Designated as safety issue: No ]Evaluation is performed using Response Evaluation Criteria in Solid Tumors (RECIST). Each patient will be assigned one of the following categories: Complete response (CR) the disappearance of all target lesion; Partial response (PR) at least a 30% decrease; Progressive disease (PD) at least a 20% increase, or the appearance of one or more new lesions; Stable disease (SD) neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease; early death from malignant disease; unknown (insufficient evaluation to determine response status).
- IL-2 Effect of Immune Function [ Time Frame: Baseline and 4 Weeks After Dosing with Salmonella typhimurium ] [ Designated as safety issue: No ]The in-vivo (within the living body) production of IL-2 and its effect on immune function will be tested using peripheral blood lymphocytes.
|Study Start Date:||April 2010|
|Study Completion Date:||June 2014|
|Primary Completion Date:||January 2014 (Final data collection date for primary outcome measure)|
Experimental: Treatment with Salmonella typhimurium
Patients will receive (a minimum of 3 patients) escalating doses of Salmonella typhimurium to achieve a maximum tolerated dose (MTD).
Biological: Salmonella typhimurium
Attenuated Salmonella typhimurium (virulent strain x4550) will be given orally in escalating dose groups: Level 1 = 10^5, Level 2 = 10^6, Level 3 = 10^7, Level 4 = 10^8, Level 5 = 10^9, Level 6 = 10^10.
This phase I study will be done to evaluate a dose escalation scheme of oral administration of an attenuated strain of Salmonella typhimurium expressing human interleukin-2 (IL-2) in patients with unresectable hepatic metastases from a solid tumor cancer. Standard Phase I dose escalation scheme will be used to determine the MTD of Samonella typhimurium. Six dose levels of Salmonella will be studied with a minimum of 3 patients enrolled in a dose level.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01099631
|United States, Minnesota|
|Edward W. Greeno, MD|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Edward W. Greeno, MD||Masonic Cancer Center, University of Minnesota|