Prevention of Irinotecan Induced Diarrhea by Probiotics

Study Overview
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Brief Summary
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Irinotecan is one of key drug used in the treatment of colorectal cancer. The incidence of irinotecan induced diarrhea varies between 60-90%, with severe diarrhea in 20-40%. The main cause of diarrhea is one of irinotecan metabolites, SN-38 which is in the liver glucuronidated and subsequently expelled into the intestine. Due to the bacterial enzyme beta-D-glucuronidase in intestinal lumen it is deconjugated. This form causes direct damage of intestinal mucosa associated with malabsorption and the development of diarrhea. It is known that probiotic bacteria, reduce activity of intestinal beta-D-glucuronidase and therefore these bacteria could be applied in the prevention of diarrhea in patients treated by this food supplement. Given their low toxicity, good tolerability, probiotics may be an important part of supportive therapy. This is a first study aimed to determine the effectiveness of the probiotics in the prophylaxis of irinotecan induced diarrhea due to reduction intestinal beta-D-glucuronidase activity.

Official Title
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Prevention of Irinotecan Induced Diarrhea by Probiotics. A Phase III Study

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Dietary Supplement: Probiotic formula
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: signed written informed consent histologically proven colorectal cancer patients started new line of chemotherapy based on irinotecan ECOG PS 0 - 1 at study entry life expectancy more than 3 months absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; Exclusion Criteria: impossibility to take oral medication active infection treated by antibiotic therapy ileostomy hypersensitivity to study drug any concurrent malignancy other than non-melanoma skin cancer, no other cancer in past 5 years. serious concomitant systemic disorders or diseases incompatible with the study (at the discretion of investigator )

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotics<br>Patients receiving probiotics. | Dietary Supplement: Probiotic formula<br>* Probiotic formula Colon DophilusTM , will be administered at a dose of 3x1 cps per day orally for 12 weeks. In the first cycle the starting dose is 3x1 cps per day. In other cycles the starting dose is 3x1 cps per day, or the dose according to dose adjustments from the previous treatment cycle.<br>|
| Placebo Comparator: Placebo<br>Patients receiving placebo | Dietary Supplement: Placebo<br>* Placebo capsules will be administered at a dose of 3x1 cps per day orally for 12 weeks. In the first cycle the starting dose is 3x1 cps per day. In other cycles the starting dose is 3x1 cps per day, or the dose according to dose adjustments from the previous treatment cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevention of grade 3-4 diarrhea by probiotics in patients treated by irinotecan based chemotherapy |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevention of any grade of diarrhea |  | 2 years | 
| Number of patients with any grade 3 or 4 toxicity or SAE related toxicity. | Number of patients with any grade 3 or 4 toxicity or SAE related toxicity according to NCI Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE). | 2 years | 
| Number of patients with any grade gastrointestinal symptoms | Number of patients with any grade gastrointestinal symptoms (enteritis, colitis, constipation, abdominal distension, bloating, flatulence, gastritis, dyspepsia,nausea, vomiting) according to NCI Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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probiotics, diarrhoea, prevention, colon cancer, irinotecan