Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Carcinoma, Hepatocellular

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Biliary Tract Cancer

Patients will receive (a minimum of 3 patients) escalating doses of Salmonella typhimurium to achieve a maximum tolerated dose (MTD).

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.

Salmonella typhimurium

Edward W. Greeno, MD

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.

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.

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

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

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.

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).

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.

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.

Masonic Cancer Center, University of Minnesota

Patients received Level 1 = 10\^5th dose of Salmonella typhimurium

Salmonella Typhimurium 10 to the 5 th - Level 1

Patients received Level 2 = 10\^6th dose of Salmonella typhimurium

Salmonella Typhimurium 10 to the 6 th - Level 2

Patients received Level 3 = 10\^7th dose of Salmonella typhimurium

Salmonella Typhimurium 10 to the 7 th - Level 3

Patients received Level 4 = 10\^8th dose of Salmonella typhimurium

Salmonella Typhimurium 10 to the 8 th - Level 4

Patients received Level 5 = 10\^9th dose of Salmonella typhimurium

Salmonella Typhimurium 10 to the 9 th - Level 5

Patients received Level 6 = 10\^10th dose of Salmonella typhimurium

Salmonella Typhimurium 10 to the 10 th - Level 6

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Daniel Saltzman

Salmonella Typhimurium 10 to the 9th - Level 5

Number of Participants With Dose Limiting Events to Determine the Maximum Tolerated Dose (MTD) of Salmonella Typhimurium

Number of Participants With Complete Response to Treatment

Before administration

After administration

Patients received Level 4 = 10\^8 th dose of Salmonella typhimurium

Patients received Level 1 = 10\^10 th dose of Salmonella typhimurium

One patient in 10 to the 6 th - Level 2 arm was not evaluable. One patient in 10 to the 7 th - Level 3 arm was not evaluable. Two patients in 10 to the 8 th - Level 4 arm were not evaluable. Two patients in 10 to the 9th - Level 5 arm were not evaluable. Two patients in 10 to the 10th - Level 6 arm were not evaluable.

Peripheral Blood NK Cells Count

Patients received Level 2 = 10\^6 th dose of Salmonella typhimurium

Patients received Level 3 = 10\^7 th dose of Salmonella typhimurium

Patients received Level 5 = 10\^10 th dose of Salmonella typhimurium

Patients received Level 6 = 10\^10 th dose of Salmonella typhimurium

Peripheral Blood T Cells Count

Patients received Level 1 = 10\^5 dose of of Salmonella typhimurium

Patients received Level 4 = 10\^7th dose of Salmonella typhimurium

Spots Global Cancer Trial Database for IL-2 Expressing, Attenuated Salmonella Typhimurium in Unresectable Hepatic Spread

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