Colon cancer Cancer Colon cancer
Conditions
Interventions
Amended as of 25/11/2008:
From induction of anaesthesia, patients will be administered 250 ml of 2% taurolidine or normal saline four times daily intravenously for four days.
Initial information at
Sponsors
Geistlich Pharma AG (Switzerland)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Initial information at time of registration: 1. Patients of both genders who are 18 to 75 years of age 2. Patients with a solitary, non-metastatic extraperitoneal colonic tumour that already has been histologically confirmed 3. Patient has given full written informed consent 4. Elective setting Added as of 25/11/2008: 5. Negative pregnancy test in women of childbearing age
Exclusion criteria
Exclusion criteria: Amended as of 25/11/2008: 1. Rectal tumours (within 15 cm of the anal orifice) 2. Known allergy to taurolidine/taurine 3. Pregnant and lactating women 4. Liver disease: 4.1. Abnormal liver function tests (LFTs) greater than 2 times upper limit of normal (ULN) 4.2. International normalised ratio (INR) greater than 1.5 5. Renal disease: 5.1. Creatinine greater than 180 (women), greater than 150 (men) 5.2. Serum sodium less than 132 or greater than 145 6. Blood dyscrasia: 6.1. Neutropenia less than 1500 cells/cm^3 6.2. Thrombocytopenia less than 100,000 cells/cm^3 7. Intestinal obstruction 8. Infiltration of adjacent organs 9. Tumour diameter greater than 8 cm on computed tomography (CT) scan 10. Severe obesity (body mass index greater than 32 kg/m^2) 11. Operative risk greater than American Society of Anaesthesiologists (ASA) - III 12. Another cancer/malignant disease other than non melanoma skin cancer 13. Coexisting active inflammatory disorder (including active Rheumatoid Arthritis [RA], Inflammatory Bowel Disease [IBD], Systemic Lupus Erythematosus [SLE]) 14. Immunocompromised: 14.1. Corticosteroids 14.2. Immunosuppressive drugs 14.3. Patients with human immunodeficiency virus (HIV), chronic active hepatitis B or C virus 15. Active infection Initial information at time of registration: 1. Known allergy to taurolidine/taurine 2. Pregnancy and lactation 3. Liver disease (abnormal Liver Function Test [LFT's] results or International Normalised Ratio [INR] greater than 1.5) 4. Renal disease 5. History of electrolyte imbalance 6. Blood dyscrasia (neutropenia less than 1500 cells/cm^3, thrombocytopenia less than 100,000 cells/cm^3) 7. Intestinal obstruction 8. Infiltration of adjacent organs 9. Tumour diameter greater than 8 cm on Computerised Tomography (CT) scan 10. Severe obesity (body mass index greater than 32 kg/m^2) 11. Operative risk greater than American Society of Anaesthesiologists (ASA) grade III 12. Another cancer/malignant disease 13. Another chronic inflammatory disorder (e.g. Rheumatoid Arthritis [RA], Inflammatory Bowel Disease [IBD], Systemic Lupus Erythematosus [SLE]) 14. Immunocompromised 15. Active infection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Amended as of 25/11/2008: 1. Percent change in taurolidine as compared to control group in mean day 1 IL-6 relative to mean baseline IL-6. Mean day-1 lL-6 defined as mean of available values from (+3, +6, +24 hours post-induction). Mean baseline defined as mean of available pre-op IL-6 levels. Initial information at time of registration: The following will be measured twice pre-operatively and at 4 hours, 24 hours, 48 hours, 3 days and 5 days post-operatively: 1. Pro-inflammatory cytokine levels (Interleukin-6 [IL-6], Interleukin-1-beta [IL-1beta], Tumour Necrosis Factor-alpha [TNF-alpha], Vascular Endothelial Growth Factor [VEGF]) 2. Anti-inflammatory cytokine levels (Interleukin-1-Receptor Antagonist [IL-1RA], Interleukin-10 [IL-10]) 3. C-Reactive Protein (CRP) 4. Endotoxin/Lipopolysaccharides (LPS) level The following will be measured twice pre-operatively and at 24 hours and 5 days post-operatively: 5. Natural Killer (NK) Cell and Cytotoxic T-Lymphocyte (CTL) cytotoxic activity 6. Neutrophil/monocyte receptor expression (CD11b, CD14, Toll-Like Receptor-4 [TLR4]) | — |
Secondary
| Measure | Time frame |
|---|---|
| Amended as of 25/11/2008: 1. Laboratory endpoints: 1.1. Percent change in taurolidine as compared to control group in mean day 2 and day 3 IL-6 relative to mean baseline Il-6. Mean day 2/day 3 defined as available IL-6 from 48 and 72 hours post-induction. 1.2. Percent change in taurolidine as compared to control group in mean available day 1 to day 3 versus mean baseline IL-10, endotoxin level, and C-reactive protein (CRP) 2. Clinical endpoints: 2.1. Comparison of Taurolidine with control group with regard to occurrence and severity of post-operative infections over 10 days post-operatively or until hospital discharge 2.2. Time to bowel functional recovery defined as time to first flatus or return of bowel sounds 2.3. Comparison of taurolidine with control group with regard to analgesic requirements (using ordinal ranking scale) and self assessed pain control using visual analogue scale at 24 and 72 hours post-induction 2.4. Percent tumour recurrence at 12 months following operation in taurolidine as compared to control group Tertiary outcomes: Percent change in taurolidine compared to control group in mean available day 1 - day 3 versus mean baseline: 1. Inflammatory cytokine levels (tumour necrosis factor alpha [TNF-a], vascular endothelial growth factor [VEGF], interleukin-1 receptor antagonist [IL-1ra], IL-1beta) 2. Natural Killer (NK) cell and cytotoxic T-lymphocyte (CTL) cytotoxic activity 3. Neutrophil/monocyte receptor expression (cluster of differentiation-14 [CD14], cluster of differentiation-11b [CD11b], toll-like receptor-4 [TLR4]) Safety endpoints: Comparison of routine haematological and biochemical data at day 1, 2, 3, 5, hospital discharge, and 1 month. Clinical status at hospital discharge, 1, 6 and 12 months. Initial information at time of registration: 1. Post-operative pain scores (Visual Analogue Scales [VAS]) 2. Post-operative GI function (time to first flatus and to bowel sounds) 3. Post-operative respiratory function/infections (clinic | — |
Countries
Ireland
Outcome results
None listed