Abdominal Cancer, Malignancy
Conditions
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.
Interventions
BIOLOGICALLipopolysaccharide
One tumor will be injected with 1 ug LPS (investigational drug) over approximately one minute
Sponsors
Patrick Wagner, MD, FACS
List Biological Laboratories, Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single-arm, open label, comparative, phase I safety and feasibility study, with correlative translational studies
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 patients undergoing injection of bacterial-derived immunotherapeutic toll receptor agonist (LPS) instilled via direct injection into intra-abdominal tumors during laparoscopic surgery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
A total of 12 patients with peritoneal metastases from gastrointestinal malignancies who met the inclusion criteria and were deemed suitable for a laparoscopy procedure and subsequent debulking surgery were enrolled.
Pre-assignment details
An additional patient was enrolled based on prior workup and radiographic evidence of metastatic disease, although these findings were not consistent with intraoperative findings. The patient had small, \<1 cm peritoneal nodules and was deemed not eligible for the study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized Age at enrollment | 52 Years |
| Primary malignancy site Appendiceal cancer : | 8 Participants |
| Primary malignancy site Colon cancer : | 4 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
None listed