IL-2 Expressing, Attenuated Salmonella Typhimurium in Unresectable Hepatic Spread

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01099631
Recruitment Status : Completed
First Posted : April 7, 2010
Last Update Posted : December 2, 2017
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Brief 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 Samonella typhimurium in the treatment.

Condition or disease Intervention/treatment Phase
Cancer of the Liver Liver Cancer Hepatoma Liver Neoplasms Biliary Cancer Biological: Salmonella typhimurium Phase 1

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 Samonella typhimurium. Six dose levels of Salmonella will be studied with a minimum of 3 patients enrolled in a dose level.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : April 2010
Actual Primary Completion Date : January 2014
Actual Study Completion Date : June 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of Samonella typhimurium [ Time Frame: Up to 24 Weeks After Dose of Samonella 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.

Secondary Outcome Measures :
  1. Efficacy of Salmonella typhimurium in Treating Unresectable Hepatic Metastases [ Time Frame: 8 Weeks After Treatment with Salmonella typhir ]
    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).

  2. IL-2 Effect of Immune Function [ Time Frame: Baseline and 4 Weeks After Dosing with Salmonella typhimurium ]
    The in-vivo (within the living body) production of IL-2 and its effect on immune function will be tested using peripheral blood lymphocytes.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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:

    • 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.

Exclusion Criteria:

  • 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.
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01099631

United States, Minnesota
Edward W. Greeno, MD
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Principal Investigator: Edward W. Greeno, MD Masonic Cancer Center, University of Minnesota

Responsible Party: Masonic Cancer Center, University of Minnesota Identifier: NCT01099631     History of Changes
Other Study ID Numbers: 2009LS003
0906M68041 ( Other Identifier: IRB, University of Minnesota )
Protocol #0907-991 ( Other Identifier: NIH OBA )
First Posted: April 7, 2010    Key Record Dates
Last Update Posted: December 2, 2017
Last Verified: November 2017

Keywords provided by Masonic Cancer Center, University of Minnesota:
Salmonella typhimurium
unresectable hepatic cancer
attenuated Salmonella typhimurium

Additional relevant MeSH terms:
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases