Prevention of Irinotecan Induced Diarrhea by Probiotics

Sponsor

Monsea Ltd. (Industry)

Overall Status

Completed

CT.gov ID

NCT01410955

Collaborator

Harmonium International Inc. (Industry), Pharma Agency (Other)

Enrollment

Locations

Arms

Duration (Months)

7.7

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Dietary Supplement: Probiotic formula Dietary Supplement: Placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

46 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 2011

Actual Primary Completion Date :

Dec 1, 2013

Actual Study Completion Date :

Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
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.
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.

Arm

Intervention/Treatment

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.

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.

Outcome Measures

Primary Outcome Measures

Prevention of grade 3-4 diarrhea by probiotics in patients treated by irinotecan based chemotherapy [2 years]

Secondary Outcome Measures

Prevention of any grade of diarrhea [2 years]
Number of patients with any grade 3 or 4 toxicity or SAE related toxicity. [2 years]
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).
Number of patients with any grade gastrointestinal symptoms [2 years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 )

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	St.James Hospital and Clinic	Bardejov	Slovakia	085 01
2	Oncologic Institute of St.Elisabeth OUSA	Bratislava	Slovakia	81250
3	National Cancer Institute, Slovakia	Bratislava	Slovakia	833 10
4	Zdravspol s r.o. - oncologic ambulance	Komarno	Slovakia	94501
5	POKO Poprad Ltd.	Poprad	Slovakia	058 01
6	Faculty Hospital Trencin	Trencin	Slovakia	91101