Prevention of Irinotecan Induced Diarrhea by Probiotics

NCT02819960 | Completed Phase 3 DMC

• 1 other identifier: 2
• Study Type: interventional
• Target: 233
• Locations: 1 country
• Sites: 1

Brief Summary

Diarrhea is a relatively common complication in patients with cancer. At its inception, several mechanisms participated; malabsorption on the basis of mucositis induced by chemotherapy, dysbiosis induced by broad-spectrum antibiotics and predisposition to infectious diarrhea in immunocompromised patients. Some cytostatics and their metabolites can also induce diarrhea directly due to effect on the intestinal mucosa. Use of probiotics in prevention and treatment of diarrhea relies on both the theoretical assumptions and the results of several clinical trials. Lactic acid bacteria involved in the treatment of dysbiosis, compete for substrate with pathogenic bacteria, produce bacterio-cins, increase transepithelial resistance. Their enzymatic activity affects activation or deactivation of metabolites which cause diarrhea. Production of short chain fatty acids, which are important for the maintenance of intestinal mucosal cells also contributes to their antidiarrhoeal effect. This randomized, double-blind, placebo controlled, multicentre trial was designed to evaluate potential of probiotics to prevent grade 3-4 diarrhea in patients treated by irinotecan based chemotherapy during first 6 weeks of irinotecan based chemotherapy

Conditions

Diarrhea; Cancer

Keywords

probiotics; irinotecan; diarrhea; Lactobacillus rhamnosus; Bifidobacterium animalis; prevention; chemotherapy

Outcome Measures

Primary Outcomes (1)

• Prevention of grade 3-4 diarrhea induced by irinotecan based chemotherapy

  To determine the efficacy (as measured by prevention of grade 3/4 diarrhea) of probiotic formula Probio-Tec® BG-VCap-6.5 given orally to patients with colorectal cancer starting new line of irinotecan based chemotherapy. Response will be defined as prevention of grade 3/4 diarrhea according to definition of NCI CTC version 4.0

  first 6 weeks of irinotecan based chemotherapy

Secondary Outcomes (4)

• Progression-free survival

  1 year

• Prevention of any grade of diarrhea

  6 weeks

• Prevention of other gastrointestinal symptoms

  6 weeks

• Incidence of treatment-emergent adverse events [Safety and Toxicity]

  6 weeks

Study Arms (2)

active probiotic formula

ACTIVE COMPARATOR

Intervention: Probiotic formula Probio-Tec® BG-VCap-6.5 will be administered at a dose of 3x1 cps per day orally for 6 weeks. No premedication or patient monitoring after administration of probiotic formula is required. Probiotic formula may be taken after meals or snacks to reduce stomach upset. Swallow the capsule or in case of problems with swallowing, capsule can be opened, content mixed with small amount of food. Food must not be hot. Patients should receive full supportive care during the study, including transfusion of blood and blood products, treatment with antibiotics, anti-emetics, anti-diarrheal agents, analgesics, erythropoetin, or bisphosphonates, when appropriate.

Drug: Probio-Tec® BG-VCap-6.5

placebo

PLACEBO COMPARATOR

Intervention: Maltodextrin will be used for placebo group and will be administered at a the same dose as active formula (3x1 cps per day orally for 6 weeks). Patients should receive full supportive care during the study, including transfusion of blood and blood products, treatment with antibiotics, anti-emetics, anti-diarrheal agents, analgesics, erythropoetin, or bisphosphonates, when appropriate.

Drug: Placebo

Interventions

Probio-Tec® BG-VCap-6.5 DRUG

Each capsule contents: 2 lyophilized probiotic strains, total amount of minimum 2,7x10 9 CFU/cps, ratio LGG®: BB-12® = 50% : 50% (Culture percentages are based on cell concentration and are approximate) Lactobacillus rhamnosus GG® (ATCC 53103) Bifidobacterium animalis subsp. lactis BB-12® (DSM 15954) Additives: maltodextrin, microcrystalline cellulose, silicium dioxide, magnesium stearate

Also known as: PROBIO-FIX INUM®

active probiotic formula

Placebo DRUG

Maltodextrin

Also known as: Maltodextrin

placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• signed written informed consent
• age \> 18 years
• histologically proven colorectal cancer patients starting 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;

You may not qualify if:

• impossibility to take oral medication
• active infection treated by antibiotic therapy
• ileostoma
• 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 )

Sponsors & Collaborators

• S&D Pharma SK s.r.o.: lead
• National Cancer Institute, Slovakia: collaborator

Study Sites (1)

National Cancer Institute

Bratislava, 833 10, Slovakia

Location

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MeSH Terms

Conditions

Diarrhea; Neoplasms

Interventions

maltodextrin

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Michal Mego, MD

  National Cancer Institute Bratislava

  PRINCIPAL INVESTIGATOR

• Lubos Drgona, MD

  National Cancer Institute Bratislava

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2016
• First Posted: June 30, 2016
• Study Start: March 1, 2016
• Primary Completion: August 1, 2022
• Study Completion: November 1, 2022
• Last Updated: December 14, 2022

Record last verified: 2022-12

Locations

SL (1)