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A Phase 1 Study of an IL-2 Expressing, Attenuated Salmonella Typhimurium in Patients With Unresectable Hepatic Spread From Any Non-Hematologic Primary

Phase 1
18 Years
Open (Enrolling)
Cancer of the Liver, Liver Cancer, Hepatoma, Liver Neoplasms, Biliary Cancer

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Trial Information

A Phase 1 Study of an IL-2 Expressing, Attenuated Salmonella Typhimurium in Patients With Unresectable Hepatic Spread From Any Non-Hematologic Primary

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.

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

- Any other condition which in the investigator's opinion renders the patient at high
risk for overwhelming infection

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD) of Samonella typhimurium

Outcome Description:

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.

Outcome Time Frame:

Up to 24 Weeks After Dose of Samonella typhimurium

Safety Issue:


Principal Investigator

Edward W. Greeno, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Masonic Cancer Center, University of Minnesota


United States: Food and Drug Administration

Study ID:




Start Date:

April 2010

Completion Date:

October 2013

Related Keywords:

  • Cancer of the Liver
  • Liver Cancer
  • Hepatoma
  • Liver Neoplasms
  • Biliary Cancer
  • Salmonella typhimurium
  • unresectable hepatic cancer
  • attenuated Salmonella typhimurium
  • IL-2
  • Neoplasms
  • Liver Neoplasms
  • Carcinoma, Hepatocellular
  • Biliary Tract Neoplasms



Edward W. Greeno, MD Minneapolis, Minnesota  55455