Treatment of Patients With Cancer With Genetically Modified Salmonella Typhimurium Bacteria
This study will examine the safety and toxicities of intravenously administering a genetically modified type of Salmonella bacteria (VNP20009) and its impact on tumor growth in advanced or metastatic cancer (cancer that has spread from the primary site). The first patients in the study will be given the smallest dose of VNP20009, and those who enter later will receive increasingly larger doses. This will be done to determine the maximum dose that can be given without serious side effects.
Normally, Salmonella bacteria ingested in food or water can cause diarrhea or more severe illness. The bacteria in this study are altered genetically so they can be injected through a vein and circulate in the blood with less likelihood of causing side effects. It is believed that the bacteria will travel in the blood to the tumor and infect it. In studies of mice, tumor growth slowed in animals whose tumors were infected with VNP0009.
Patients with advanced or metastatic cancer 18 years of age or older whose disease is not responding to standard treatment, or for which there is no treatment, may be eligible for this study. Candidates will undergo a medical history and physical examination, including blood tests, scans, X-rays, electrocardiogram, and urine, stool and blood cultures.
Study participants will be admitted to the hospital for 2 to 4 days. On day 1, they will receive the first dose of VNP0009, infused over a 30-minute period through an intravenous catheter (a small plastic tube inserted into a vein). Blood will be drawn every day to determine if the bacteria are still in the body. After discharge, patients will return to the hospital on days after approximately 1-2 weeks and again after 4-5 weeks for additional blood tests to measure levels of the bacteria and for collection of blood, urine and stool samples. Patients whose tumors are on or just beneath the skin may be asked to have one or two tumors removed surgically.
Patients will have tests after approximately 4-5 weeks, including CTs and X-rays, to determine the size and extent of the tumor. Patients whose tumor remained the same size or smaller than before starting treatment, and whose side effects were acceptable will be offered a second treatment cycle. Those whose tumor grew during treatment will be taken off the study. Patients remaining in the study will begin the second cycle on approximately day 36. Tumor growth will be evaluated again between days 64 and 70, and a third cycle will be offered to patients whose tumors have remained stable or have shrunk. Patients may have up to 12 treatment cycles as long as evaluations continue to show the tumor is stable or shrinking. Completing all 12 cycles takes about 13 months. Patients will continue to be evaluated after treatment ends, if they agree to continued follow-up.
Patients must follow health precautions to prevent infecting others with Salmonella bacteria as long as they, themselves, remain infected. These include, for example, stringent hand washing practices and avoiding contact with people with weakened immune systems. All the precautions will be explained to the study participants.
Patients who leave the study must take antibiotic therapy to rid the body of any remaining bacteria. They will return for urine, stool and blood cultures 30 days after the start of antibiotics, and may undergo three types of scans to look for sites of infection. Treatment will be given as needed.
|Study Design:||Endpoint Classification: Safety Study
Primary Purpose: Treatment
|Official Title:||A Phase I Trial of a Live, Genetically Modified Salmonella Typhimurium (VNP20009) for the Treatment of Cancer by Intravenous Administration|
|Study Start Date:||March 2000|
|Estimated Study Completion Date:||October 2002|
Please refer to this study by its ClinicalTrials.gov identifier: NCT00004988
|United States, Maryland|
|National Cancer Institute (NCI)|
|Bethesda, Maryland, United States, 20892|