CancerPhase 1NCT00004988
Treatment of Patients With Cancer With Genetically Modified Salmonella Typhimurium Bacteria
A Phase 1 study testing VNP20009 in people with Cancer and Neoplasm, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Cancer, Neoplasm, Neoplasm Metastasis
- What is being tested?
- VNP20009
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2000to Oct 2002
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Only patients must have advanced and/or metastatic, histologically documented solid tumors will be included.
- Patients must have a solid tumor which is no longer considered responsive to available conventional modalities or treatments (failed any known standard curative or palliative therapy for that disease), or a previously untreated tumor for which no effective standard treatment is available. Patients must have measurable or evaluable metastatic disease.
- All patients must have at least one tumor mass suitable and easily accessible for excisional biopsy or fine needle aspiration. The procedure must be able to be performed with minimum morbidity and discomfort to the patient.
- ECOG performance status of 0 or 1.
- Patients must be 18 years of age or older.
- Patients must have expected survival of at least 3 months.
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- Men and women of child-bearing potential (i.e., women who are premenopausal or not surgically sterile), must use acceptable contraceptive methods (abstinence, intrauterine device (IUD), oral contraceptive or double barrier device), and women must have a negative serum or urine pregnancy test 1 week before beginning treatment on this trial. Nursing patients are also excluded.
- Must be able and willing to give written informed consent.
- Must be able and willing to execute a durable power of attorney (DPA).
- No treatment with cytotoxic agents, or treatment with biologic agents within 3 weeks prior to treatment with VNP20009. Must have fully recovered from toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities.
- Patients must have the following clinical laboratory values: (a) Granulocyte count of greater than or equal to 2,000/mm(3); (b) Platelets greater than or equal to 100,000/mm(3); (c) Serum creatinine less than or equal to 1.5 mg/dl; (d) Bilirubin less than or equal to 1.6 mg/dl, ALT, AST less than or equal to 1.5 times the upper limit of normal, alkaline phosphatase less than or equal to 1.5 times the upper limit of normal, (ALT, AST, alkaline phosphatase less than or equal to 3 times the upper limit in presence of liver metastases); (e) Prothrombin Time (PT) and activated partial thromboplastin time (aPTT) less than or equal to 1.5 times the upper limit of normal; (f) Hematocrit greater than or equal to 30% (may be corrected by transfusion); (g) Patients should have daily T max less than or equal to 38.0 degrees C.
Who cannot join
- Patients with any one of the following criteria will not be eligible for study participation:
- Diagnosis of lymphoma or other hematologic malignancy.
- An artificial implant that cannot be removed (e.g., heart valves, prosthetic hips or knees, or other devices) which could represent a nidus of infection.
- Known history of valvular disease or severe arteriosclerosis. Patients with a significant murmur on physical examination will undergo an echocardiogram to evaluate for valvular disease.
- Known clinically significant atherosclerotic disease, peripheral vascular disease, or arterial aneurysm(s) or arterial or venous malformations. Patients in atrial fibrillation will undergo an echocardiogram to rule out presence of thrombus, which would make them ineligible.
- An ultrasound will be performed pre-treatment in patients with intact gallbladders. No patients with any evidence of cholelithiasis or obstruction, unless they are able to undergo a simple cholecystectomy with minimal morbidity, in which case they would be eligible once they have fully recovered to their baseline status.
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- All patients will be screened with an ultrasound of the kidneys. Patients with urolithiasis will be excluded.
- Active infection of any kind, including Hepatitis B or chronic viral hepatitis.
- Documented Salmonella infections within 6 months.
- Currently using antibiotics.
- Patients with tumor fever, or fever of unknown origin or cause.
- Any known bleeding disorder.
- Patients must not have had a splenectomy or documented immunodeficiency such as HIV infection. These patients are excluded because VNP2009 may be more toxic in severely immunocompromised patients.
- Patients on steroids, immunosuppressives, or any other medications that can directly or indirectly suppress the immune system.
- Presence of any other life-threatening illness, such as unstable angina, severe oxygen dependent chronic obstructive pulmonary disease (COPD), end stage liver or renal disease.
- Requirement immediate palliative treatment of any kind including surgery.
- Presence of a known brain metastases. Patients with previously treated brain metastases and no evidence of recurrence are eligible.
- Unwilling and unable to follow protocol requirements.
- Hypersensitivity (history of allergic reactions) to quinolone or cephalosporin antibodies.
- Patients who have been vaccinated against Salmonella Typhii within the past 6 months.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Cancer Institute (NCI)
Bethesda, Maryland, 20892
About this study
Official title: A Phase I Trial of a Live, Genetically Modified Salmonella Typhimurium (VNP20009) for the Treatment of Cancer by Intravenous Administration
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.
Read more
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.
Read the detailed description
Patients with metastatic cancer will receive the intravenous injection of live genetically modified Salmonella typhimurium. This bacteria has been genetically modified to alter its pathogenicity and to attempt to increase its localization to sites of growing cancer. Cohorts of patients will receive increasing doses of the bacteria to establish the maximum tolerated dose.
- Conditions
- Cancer, Neoplasm, Neoplasm Metastasis
- Being tested
- VNP20009
- Keywords
- Anti-Tumor Effects, Maximum Tolerated Dose (MTD), Metastatic Cancer, Pharmacokinetics, Solid Tumors, Tumor
- Medical subject headings
- Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VNP20009Drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2000 (estimated)
- Study startMar 2000
- Study completionOct 2002
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Enrolment
- 45 participants
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00004988
- Sponsor's protocol ID
- 000098
- Other IDs
- 00-C-0098
- Status last verified
- Oct 2002
- First submitted
- 18 Mar 2000
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Pawelek JM, Low KB, Bermudes D. Tumor-targeted Salmonella as a novel anticancer vector. Cancer Res. 1997 Oct 15;57(20):4537-44.
PubMed 9377566Low KB, Ittensohn M, Le T, Platt J, Sodi S, Amoss M, Ash O, Carmichael E, Chakraborty A, Fischer J, Lin SL, Luo X, Miller SI, Zheng L, King I, Pawelek JM, Bermudes D. Lipid A mutant Salmonella with suppressed virulence and TNFalpha induction retain tumor-targeting in vivo. Nat Biotechnol. 1999 Jan;17(1):37-41. doi: 10.1038/5205.
PubMed 9920266Chen JJ, Sun Y, Nabel GJ. Regulation of the proinflammatory effects of Fas ligand (CD95L). Science. 1998 Nov 27;282(5394):1714-7. doi: 10.1126/science.282.5394.1714.
PubMed 9831564
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of a Live, Genetically Modified Salmonella Typhimurium (VNP20009) for the Treatment of Cancer by Intravenous Administration
- ClinicalTrials.gov ID
- NCT00004988
- Acronym / sponsor ID
- 000098
- Conditions
- Cancer, Neoplasm, Neoplasm Metastasis
- Keywords
- Anti-Tumor Effects, Maximum Tolerated Dose (MTD), Metastatic Cancer, Pharmacokinetics, Solid Tumors, Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Mar 2000
- Study completion
- Oct 2002
- First posted
- 20 Mar 2000 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Patients with metastatic cancer will receive the intravenous injection of live genetically modified Salmonella typhimurium. This bacteria has been genetically modified to alter its pathogenicity and to attempt to increase its localization to sites of growing cancer. Cohorts of patients will receive increasing doses of the bacteria to establish the maximum tolerated dose.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- Only patients must have advanced and/or metastatic, histologically documented solid tumors will be included.
- Patients must have a solid tumor which is no longer considered responsive to available conventional modalities or treatments (failed any known standard curative or palliative therapy for that disease), or a previously untreated tumor for which no effective standard treatment is available. Patients must have measurable or evaluable metastatic disease.
- All patients must have at least one tumor mass suitable and easily accessible for excisional biopsy or fine needle aspiration. The procedure must be able to be performed with minimum morbidity and discomfort to the patient.
- ECOG performance status of 0 or 1.
- Patients must be 18 years of age or older.
Key exclusion criteria (20 listed)
- Patients with any one of the following criteria will not be eligible for study participation:
- Diagnosis of lymphoma or other hematologic malignancy.
- An artificial implant that cannot be removed (e.g., heart valves, prosthetic hips or knees, or other devices) which could represent a nidus of infection.
- Known history of valvular disease or severe arteriosclerosis. Patients with a significant murmur on physical examination will undergo an echocardiogram to evaluate for valvular disease.
- Known clinically significant atherosclerotic disease, peripheral vascular disease, or arterial aneurysm(s) or arterial or venous malformations. Patients in atrial fibrillation will undergo an echocardiogram to rule out presence of thrombus, which would make them ineligible.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VNP20009 | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 9377566Pawelek JM, Low KB, Bermudes D. Tumor-targeted Salmonella as a novel anticancer vector. Cancer Res. 1997 Oct 15;57(20):4537-44.
- Background: PubMed 9920266Low KB, Ittensohn M, Le T, Platt J, Sodi S, Amoss M, Ash O, Carmichael E, Chakraborty A, Fischer J, Lin SL, Luo X, Miller SI, Zheng L, King I, Pawelek JM, Bermudes D. Lipid A mutant Salmonella with suppressed virulence and TNFalpha induction retain tumor-targeting in vivo. Nat Biotechnol. 1999 Jan;17(1):37-41. doi: 10.1038/5205.
- Background: PubMed 9831564Chen JJ, Sun Y, Nabel GJ. Regulation of the proinflammatory effects of Fas ligand (CD95L). Science. 1998 Nov 27;282(5394):1714-7. doi: 10.1126/science.282.5394.1714.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing VNP20009 in people with Cancer and Neoplasm, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00004988, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.