Feasibility Study of Intra-Tumoral Lipopolysaccharide Immunotherapy for Intra-Abdominal

Phase 1

Completed

• Conditions: Malignancy; Abdominal Cancer
• Interventions: Biological: Lipopolysaccharide

• Registration Number: NCT05751837
• Lead Sponsor: Patrick Wagner, MD, FACS

Brief Summary

The purpose of this research study is to determine whether a sterile bacteria wall chemical, called lipopolysaccharide (LPS), can be injected safely into abdominal tumors during routine laparoscopic surgery performed as a preliminary procedure in patients who will subsequently undergo a larger planned operation to remove abdominal tumors. The researchers will biopsy the tumor before injection and then again at the time of the larger operation to assess whether any effect of the treatment can be measured.

Detailed Description

Immunotherapy for advanced cancers of the abdomen can be quite effective, but not all tumors are responsive to this type of treatment. There is intense interest in new methods to convert non-responsive tumors into responsive tumors. One such method is to inject chemical constituents of micro-organisms into tumors in order to stimulate the immune system to recognize the tumor as foreign and mount an immune response to treatment.

Provide a concise and brief, one-paragraph summary of your research project. Include a summary of the problem, the main objective and rationale of your project; a brief description of the experimental approach and methods; a concise description/summary of the most important results that you hope to obtain; and why think your results will be significant

Study Timeline

• Study First Submitted: 2023-02-02
• Study First Submitted QC: 2023-02-28
• Study First Posted: 2023-03-02
• Study Start: 2023-03-16
• Primary Completion: 2024-05-30
• Study Completion: 2024-05-30
• Status Verified: 2024-07
• Last Update Submitted: 2024-12-05
• Last Update Posted: 2024-12-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

1. Males or females age 18 to 99 years
2. Pre-menopausal women less than or equal to18 years of age must have a negative urine/serum pregnancy test prior to standard-of-care surgery and investigational treatment.
3. Participants must have an advanced intra-abdominal tumor, including metastatic or recurrent, biopsy-proven, digestive tract tumors.
4. Participants must have at least two index non-visceral intra-abdominal tumors that are grossly visible, >1cm3 in volume, and amenable to biopsy and injection of investigational drug or control solution at the time of laparoscopy.
5. Participants must be planning or scheduled to undergo a standard-of-care abdominal laparoscopic surgical procedure at AGH or WPH and be potentially eligible for a second, definitive operation to remove the tumor(s) pending the findings during laparoscopy.
6. Must be able to read and understand English and consent for themselves

Exclusion Criteria

1. Pregnant or lactating females

2. Investigational drug use within 30 days prior to enrollment.

3. Immunosuppressive medication including corticosteroids within 30 days prior to enrollment.

4. Active chemotherapy or radiotherapy within 4 weeks of investigational agent injection.

5. Active infection requiring systemic therapy or causing fever >38.1 degree C or unexplained fever >38.1 degree C within seven days prior to investigational agent injection

6. Laboratory abnormalities, drawn according to standard clinical care in anticipation of upcoming surgery outside the following limits:

   AST/SGOT > 1.5 times the upper limit of normal ALT/SGPT > 1.5 times the upper limit of normal Total bilirubin > 1.5 times the upper limit of normal Creatinine > 1.5 times the upper limit of normal Hemoglobin < 9 gm/dL White blood cell count < 3,000/ mm3 Platelet count < 70,000/mm3 INR >1.5 times the upper limit of normal PTT >1.5 times the upper limit of normal

7. History of allergic reaction to the investigational agent carrier solution.

8. Medical contra-indication or allergic reaction to acetaminophen or NSAIDs.

9. Participants who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.

10. Adverse events from prior therapy that have not resolved to CTCAE version 5 grade < and equal to1 prior to enrollment

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment Arm	Lipopolysaccharide	Injection of Lipopolysaccharide into one abdominal tumor

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	30 Days	The number, nature and severity of adverse events as assessed by CTCAE v 4.0 will be determined in a series of six patients undergoing injection of bacterial-derived immunotherapeutic toll receptor agonist (LPS) instilled via direct injection into intra-abdominal tumors during laparoscopic surgery.

Secondary Outcome Measures

Name	Time	Method
Alteration in Cellular and Soluble Immune Biomarkers in Injected Tumors	30 days	Changes in intra-tumoral leukocyte subgroup densities and soluble immune biomarker concentrations will be assessed in injected tumors and compared against non-injected tumors.

Trial Locations

Locations (2)

Allegheny Health Network Allegheny General Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

Allegheny Health Network West Penn Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States