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

NCT01099631 | Completed Phase 1 Results DMC

• 3 other identifiers: 2009LS0030906M68041Protocol #0907-991
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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 Salmonella typhimurium in the treatment.

Conditions

Cancer of the Liver; Liver Cancer; Hepatoma; Liver Neoplasms; Biliary Cancer

Keywords

Salmonella typhimurium; unresectable hepatic cancer; attenuated Salmonella typhimurium; IL-2

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 24 Weeks After Dose of Salmonella typhimurium

Secondary Outcomes (3)

• Number of Participants With Complete Response to Treatment

  8 Weeks After Treatment with Salmonella Typhimurium

• Peripheral Blood NK Cells Count

  Baseline and 5 Weeks After Dosing with Salmonella typhimurium

• Peripheral Blood T Cells Count

  Baseline and 5 Weeks After Dosing with Salmonella typhimurium

Study Arms (6)

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).

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).

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).

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).

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).

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).

Biological: Salmonella typhimurium

Interventions

Salmonella typhimurium BIOLOGICAL

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 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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Edward W. Greeno, MD

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Liver Neoplasms; Carcinoma, Hepatocellular; Biliary Tract Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Biliary Tract Diseases

Results Point of Contact

• Title: Daniel Saltzman
• Organization: Masonic Cancer Center, University of Minnesota

saltz002@umn.edu

612 626 4214

Study Officials

• Edward W. Greeno, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2010
• First Posted: April 7, 2010
• Study Start: April 1, 2010
• Primary Completion: January 1, 2014
• Study Completion: June 1, 2014
• Last Updated: July 20, 2020
• Results First Posted: July 20, 2020

Record last verified: 2020-07

Locations

US (1)