Cancer of the LiverPhase 1NCT01099631
IL-2 Expressing, Attenuated Salmonella Typhimurium in Unresectable Hepatic Spread
A Phase 1 study testing Salmonella typhimurium in people with Cancer of the Liver and Liver Cancer, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
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 Salmonella typhimurium in the treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer of the Liver, Liver Cancer, Hepatoma
- What is being tested?
- Salmonella typhimurium
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2010to Jun 2014
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologic documentation of malignancy (any solid tumor type) that has spread to the liver and deemed unresectable, and for which no effective standard therapies are available. Patients with additional disease outside of the liver will be allowed.
- Patients may have received any number of other prior therapies; however at least 3 weeks must have passed since last dose of chemotherapy or radiotherapy (6 weeks for Nitrosoureas or Mitomycin C) prior to study entry.
- Must have recovered from all acute toxicities (defined per National Cancer Institute's Common Toxicity Criteria for Adverse Events 3.0 ≤ grade 1) associated with previous treatment.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
- Life expectancy of greater than 2 months as determined by the enrolling investigator
- Adequate organ function within 1 week of treatment start defined as:
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- Adequate bone marrow reserve: leukocytes ≥ 3,000/μl, absolute neutrophil count (ANC) ≥ 1,500/μl, platelets ≥ 100,000/μl
- Hepatic: bilirubin ≤1.5 times institutional upper limit of normal (×ULN), aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN
- Renal: serum creatinine ≤ 1.5 x ULN
- Women of child-bearing potential and sexually active men must agree to use adequate contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
Who cannot join
- Unable to take oral drugs or clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to: malabsorption syndrome, major resection of stomach or small bowel
- Receiving any other investigational agents
- Known central nervous system metastases
- Residing in a household or having close contact with pregnant women, young children (under the age of 1 year) or immune compromised persons
- Engaged in activities that might pose a risk for widespread dissemination of this organism, including, but not limited to; health care, child care, or food service.
- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations.
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- Pregnant or breastfeeding. Women of child bearing potential must have a negative serum or urine pregnancy test within 7 days of prior to the start of treatment. Pregnancy testing is not required for post-menopausal or surgically sterilized women. Breast-feeding mothers will be asked to discontinue feeding infants prior to enrolling in the study.
- Known HIV infection, need for chronic steroids or other immunosuppressant drugs, or other medical conditions that in the investigator's opinion result in a significant degree of immunosuppression. Patients without identified HIV risk factors are not required to have HIV testing to be eligible.
- Known active hepatitis B or C infection
- Known HLA B27
- Have permanent artificial implants (such as, but not limited to prosthetic valves and joints.)
- Any other condition which in the investigator's opinion renders the patient at high risk for overwhelming infection
Trial locations and contacts
1 site in 1 country.
About this study
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
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 Salmonella typhimurium in the treatment.
Read the detailed description
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 Salmonella Typhimurium. Six dose levels of Salmonella will be studied with a minimum of 3 patients enrolled in a dose level.
- Conditions
- Cancer of the Liver, Liver Cancer, Hepatoma, Liver Neoplasms, Biliary Cancer
- Being tested
- Salmonella typhimurium
- Keywords
- Salmonella typhimurium, unresectable hepatic cancer, attenuated Salmonella typhimurium, IL-2
- Medical subject headings
- Liver Neoplasms, Carcinoma, Hepatocellular, Biliary Tract Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Salmonella typhimuriumBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| Salmonella typhimurium 10 to the 5th - Level 1 | Experimental | Patients will receive (a minimum of 3 patients) escalating doses of Salmonella typhimurium to achieve a maximum tolerated dose (MTD). Receives: Biological: Salmonella typhimurium |
| Salmonella typhimurium 10 to the 6th -- Level 2 | Experimental | Patients will receive (a minimum of 3 patients) escalating doses of Salmonella typhimurium to achieve a maximum tolerated dose (MTD). Receives: Biological: Salmonella typhimurium |
| Salmonella typhimurium 10 to the 7th -- Level 3 | Experimental | Patients will receive (a minimum of 3 patients) escalating doses of Salmonella typhimurium to achieve a maximum tolerated dose (MTD). Receives: Biological: Salmonella typhimurium |
| Salmonella typhimurium 10 to the 8th - Level 4 | Experimental | Patients will receive (a minimum of 3 patients) escalating doses of Salmonella typhimurium to achieve a maximum tolerated dose (MTD). Receives: Biological: Salmonella typhimurium |
| Salmonella typhimurium 10 to the 9th - Level 5 | Experimental | Patients will receive (a minimum of 3 patients) escalating doses of Salmonella typhimurium to achieve a maximum tolerated dose (MTD). Receives: Biological: Salmonella typhimurium |
| Salmonella typhimurium 10 to the 10th - Level 1 | Experimental | Patients will receive (a minimum of 3 patients) escalating doses of Salmonella typhimurium to achieve a maximum tolerated dose (MTD). Receives: Biological: Salmonella typhimurium |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Limiting Events to Determine the Maximum Tolerated Dose (MTD) of Salmonella Typhimurium
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.
Measured: Up to 24 Weeks After Dose of Salmonella typhimurium
Secondary outcomes (3)
Number of Participants With Complete Response to Treatment
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).
Measured: 8 Weeks After Treatment with Salmonella Typhimurium
Peripheral Blood NK Cells Count
Patients receiving doses of 10^5 through 10^10 Colony forming units of Salmonella typhimurium had their peripheral blood flow cytometry performed to identify the NK (Natural killer) cells population (CD8-, CD4-, CD49b+) prior to administration and at 5 weeks post administration.
The flow cytometry data below was gathered by gating on the lymphocyte population of cells in the patient's blood, as determined by FSC vs. SSC. The mean percentage of NK cells in sample's lymphocyte population is given.
Measured: Baseline and 5 Weeks After Dosing with Salmonella typhimurium
Peripheral Blood T Cells Count
Patients receiving doses of 10^5 through 10^10 Colony forming units of Salmonella typhimurium had their peripheral blood flow cytometry performed to identify the NK (Natural killer) cells population (CD25+, FoxP3+) prior to administration and at 5 weeks post administration.
The flow cytometry data below was gathered by gating on the lymphocyte population of cells in the patient's blood, as determined by FSC vs. SSC. The mean percentage of T cells in sample's lymphocyte population is given.
Measured: Baseline and 5 Weeks After Dosing with Salmonella typhimurium
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2010 (estimated)
- Study startApr 2010
- Primary completionJan 2014
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cancer of the LiverStudies of the same condition, open and under way.
- More trials run by Masonic Cancer Center, University of MinnesotaThe 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
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Edward W. Greeno, MD, Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01099631
- Sponsor's protocol ID
- 2009LS003
- Other IDs
- 0906M68041, Protocol #0907-991
- Status last verified
- Jul 2020
- First submitted
- 6 Apr 2010
- Last updated
- 20 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01099631
- Acronym / sponsor ID
- 2009LS003
- Conditions
- Cancer of the Liver, Liver Cancer, Hepatoma, Liver Neoplasms, Biliary Cancer
- Keywords
- Salmonella typhimurium, unresectable hepatic cancer, attenuated Salmonella typhimurium, IL-2
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- Apr 2010
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 7 Apr 2010 (estimated)
- Results
- Posted 20 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 Salmonella typhimurium in the treatment.
Detailed description
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 Salmonella Typhimurium. Six dose levels of Salmonella will be studied with a minimum of 3 patients enrolled in a dose level.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Salmonella typhimurium 10 to the 5th - Level 1 | Experimental | Biological: Salmonella typhimuriumPatients will receive (a minimum of 3 patients) escalating doses of Salmonella typhimurium to achieve a maximum tolerated dose (MTD). |
| Salmonella typhimurium 10 to the 6th -- Level 2 | Experimental | Biological: Salmonella typhimuriumPatients will receive (a minimum of 3 patients) escalating doses of Salmonella typhimurium to achieve a maximum tolerated dose (MTD). |
| Salmonella typhimurium 10 to the 7th -- Level 3 | Experimental | Biological: Salmonella typhimuriumPatients will receive (a minimum of 3 patients) escalating doses of Salmonella typhimurium to achieve a maximum tolerated dose (MTD). |
| Salmonella typhimurium 10 to the 8th - Level 4 | Experimental | Biological: Salmonella typhimuriumPatients will receive (a minimum of 3 patients) escalating doses of Salmonella typhimurium to achieve a maximum tolerated dose (MTD). |
| Salmonella typhimurium 10 to the 9th - Level 5 | Experimental | Biological: Salmonella typhimuriumPatients will receive (a minimum of 3 patients) escalating doses of Salmonella typhimurium to achieve a maximum tolerated dose (MTD). |
| Salmonella typhimurium 10 to the 10th - Level 1 | Experimental | Biological: Salmonella typhimuriumPatients will receive (a minimum of 3 patients) escalating doses of Salmonella typhimurium to achieve a maximum tolerated dose (MTD). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Histologic documentation of malignancy (any solid tumor type) that has spread to the liver and deemed unresectable, and for which no effective standard therapies are available. Patients with additional disease outside of the liver will be allowed.
- Patients may have received any number of other prior therapies; however at least 3 weeks must have passed since last dose of chemotherapy or radiotherapy (6 weeks for Nitrosoureas or Mitomycin C) prior to study entry.
- Must have recovered from all acute toxicities (defined per National Cancer Institute's Common Toxicity Criteria for Adverse Events 3.0 ≤ grade 1) associated with previous treatment.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
- Life expectancy of greater than 2 months as determined by the enrolling investigator
Key exclusion criteria (12 listed)
- Unable to take oral drugs or clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to: malabsorption syndrome, major resection of stomach or small bowel
- Receiving any other investigational agents
- Known central nervous system metastases
- Residing in a household or having close contact with pregnant women, young children (under the age of 1 year) or immune compromised persons
- Engaged in activities that might pose a risk for widespread dissemination of this organism, including, but not limited to; health care, child care, or food service.
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 |
|---|---|---|
| Salmonella typhimuriumAttenuated 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. | Biological | Salmonella typhimurium 10 to the 10th - Level 1, Salmonella typhimurium 10 to the 5th - Level 1, Salmonella typhimurium 10 to the 6th -- Level 2, Salmonella typhimurium 10 to the 7th -- Level 3, Salmonella typhimurium 10 to the 8th - Level 4, Salmonella typhimurium 10 to the 9th - Level 5 |
Primary outcome
Number of Participants With Dose Limiting Events to Determine the Maximum Tolerated Dose (MTD) of Salmonella Typhimurium
Time frame: Up to 24 Weeks After Dose of Salmonella typhimurium
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.
3 secondary outcomes
Number of Participants With Complete Response to Treatment
Time frame: 8 Weeks After Treatment with Salmonella Typhimurium
Peripheral Blood NK Cells Count
Time frame: Baseline and 5 Weeks After Dosing with Salmonella typhimurium
Peripheral Blood T Cells Count
Time frame: Baseline and 5 Weeks After Dosing with Salmonella typhimurium
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Edward W. Greeno, MD principal investigator
Masonic Cancer Center, University of Minnesota
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 Salmonella typhimurium in people with Cancer of the Liver and Liver Cancer, run by Masonic Cancer Center, University of Minnesota 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 12 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 20 Jul 2020. 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?
Yes. Results are posted in the registry (first posted 20 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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.
What does the primary outcome measure?
Number of Participants With Dose Limiting Events to Determine the Maximum Tolerated Dose (MTD) of Salmonella Typhimurium (time frame: Up to 24 Weeks After Dose of Salmonella typhimurium). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Jul 2020.