Treatment of Patients With Cancer With Genetically Modified Salmonella Typhimurium Bacteria
Status:
Completed
Trial end date:
2002-10-01
Target enrollment:
Participant gender:
Summary
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.