IL-2 Expressing, Attenuated Salmonella Typhimurium in Unresectable Hepatic Spread
Condition: Cancer of the Liver; Liver Cancer; Hepatoma; Liver Neoplasms; Biliary Cancer
MeSH terms: Liver Neoplasms
Intervention: Salmonella typhimurium
Intervention description: 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.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Salmonella typhimurium; unresectable hepatic cancer; attenuated Salmonella typhimurium; IL-2

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.
    

Eligibility criteria:

        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