Prevention of Irinotecan Induced Diarrhea by Probiotics

This study has been completed.
Sponsor:
Collaborators:
Harmonium International Inc.
Pharma Agency
Information provided by (Responsible Party):
Monsea Ltd.
ClinicalTrials.gov Identifier:
NCT01410955
First received: April 26, 2011
Last updated: January 22, 2014
Last verified: January 2014
  Purpose

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 Intervention Phase
Colorectal Cancer
Dietary Supplement: Probiotic formula
Dietary Supplement: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Prevention of Irinotecan Induced Diarrhea by Probiotics. A Phase III Study

Resource links provided by NLM:


Further study details as provided by Monsea Ltd.:

Primary Outcome Measures:
  • Prevention of grade 3-4 diarrhea by probiotics in patients treated by irinotecan based chemotherapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Prevention of any grade of diarrhea [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Number of patients with any grade 3 or 4 toxicity or SAE related toxicity. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.


Enrollment: 46
Study Start Date: December 2011
Study Completion Date: January 2014
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01410955

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

No publications provided

Responsible Party: Monsea Ltd.
ClinicalTrials.gov Identifier: NCT01410955     History of Changes
Other Study ID Numbers: 900450001
Study First Received: April 26, 2011
Last Updated: January 22, 2014
Health Authority: Slovak Republic: Ethics Committee

Keywords provided by Monsea Ltd.:
probiotics
diarrhoea
prevention
colon cancer
irinotecan

Additional relevant MeSH terms:
Colorectal Neoplasms
Diarrhea
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Signs and Symptoms, Digestive
Signs and Symptoms
Irinotecan
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014