Prevention of Irinotecan Induced Diarrhea by Probiotics

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

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Dietary supplement: Probiotic formula; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 3

Contacts and Locations

Study Locations

• Slovakia
  • Bardejov, Slovakia, 085 01
    • St.James Hospital and Clinic
  • Bratislava, Slovakia, 81250
    • Oncologic Institute of St.Elisabeth OUSA
  • Bratislava, Slovakia, 833 10
    • National Cancer Institute, Slovakia
  • Komarno, Slovakia, 94501
    • Zdravspol s r.o. - oncologic ambulance
  • Poprad, Slovakia, 058 01
    • POKO Poprad Ltd.
  • Trencin, Slovakia, 91101
    • Faculty Hospital Trencin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 )

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Patients receiving placebo	Dietary supplement: Placebo; 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.
Experimental: Probiotics; Patients receiving probiotics.	Dietary supplement: Probiotic formula; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Monsea Ltd.
• Collaborators: Harmonium International Inc.; Pharma Agency
• Investigators: Study Chair: Michal Mego, MD, PhD, National Cancer Institute, Slovakia; Study Chair: Lubos Drgona, MD, PhD, National Cancer Institute, Slovakia

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: April 26, 2011
• First Submitted That Met QC Criteria: August 4, 2011
• First Posted (Estimate): August 5, 2011

Study Record Updates

• Last Update Posted (Estimate): January 23, 2014
• Last Update Submitted That Met QC Criteria: January 22, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: probiotics; prevention; colon cancer; irinotecan; diarrhoea
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Diarrhea
• Other Study ID Numbers: 900450001