Clinical trial NCT02706184: E. Coli Nissle in Oncology
Official title: Randomized, Placebo Controlled Phase III Trial of a Microbiological Concomitant Therapy/Prevention of Chemotherapeutical Induced Diarrhea (Caused by Inflammation and an Impaired Intestinal Barrier) With E. Coli Nissle 1917 (EcN)-Suspension in Patients With Gastric and Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gastric Cancer
Colorectal Cancer
Keywords: gastric cancer
colorectal cancer
chemotherapy induced diarrhea
5-Fluoruracil
chemotherapeutic remedy
Lead sponsor: University of Hohenheim
Sponsor class: OTHER
Collaborators: name: Ardeypharm GmbH
First posted: 2016-03-11
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: In patients with gastric or colorectal cancers, where a treatment with 5-Fluoruracil in combination with other chemotherapeutic remedies (FLO, FOLFOX, FOLFOX-Bev, FOLFIRI) is planned, it shall be investigated whether E. coli Nissle suspension has an effect on duration and intensity of chemotherapy induced diarrhea.

Detailed description: Chemotherapy is used frequently for treating tumors. For many kinds of tumors, chemotherapy is an effective way of treatment. Besides the desired effects on neoplastic cells, the cytotoxic effects often lead to undesirable effects in other cells. Particularly the epithelial tissue of the gastrointestinal tract is affected, mucositis and diarrhea occur. By loss of water and electrolytes, diarrhea often make delay in chemotherapy necessary. Besides mucositis, a chemotherapy also causes changes in gut microbiota as animal models proof. It is well known, than probiotics shorten diarrhea. So far, the use of probiotics in chemotherapy patients was only investigated in one single study. Severity of diarrhea was reduced compared to placebo. Escherichia coli Nissle 1917 (EcN) is a well investigated probiotic. In cell culture, the supernatant of EcN reduced the noxious effect of 5-Fluoruracil concerning cell toxicity and disruption of barrier function.

Therefore, the aim of this study is whether in patients with gastric or colorectal cancers, where a treatment with 5-Fluoruracil in combination with other chemotherapeutic remedies (FLO, FOLFOX, FOLFOX-Bev, FOLFIRI) is planned, EcN-Suspension is capable to reduce duration and intensity of chemotherapy induced diarrhea.

Eligibility criteria: Inclusion Criteria:

* Male or female adults
* patients with gastric or colorectal cancer (stages III or IV), where a treatment with 5-Fluoruracil in combination with other chemotherapeutic remedies (FLO, FOLFOX, FOLFOX-Bev, FOLFIRI) is planned
* life expectancy of at least the trial duration
* the first administering of the product under investigation must be able to take place 72 hours before or after the beginning of the chemotherapeutical treatment, ideally at the same time
* an inclusion into the study is only possible at the beginning of the first chemotherapeutic cycle
* fertile female patients (aged 49 years or minor, the last menstruation occured in less than two years) have to be either surgically sterilized or use the same highly effective method of contraception for at least three months
* willingness to refrain from other probiotics or probiotic yoghurts, a systematic change of eating behavior should not be planned
* sufficient knowledge of german language and sufficient psychological state for being able to answer questionnaires and assessment scales
* informed written consent

Exclusion Criteria:

* Participation in other clinical trials (currently or within the last 30 days)
* intolerance against ingredients of the product under investigation
* pregnancy or lactation
* being not able to consume the product under investigation orally
* antidiarrheal therapy with antibiotics
* alcohol or drug abuse within the last six months
* any health condition (including abnormal blood parameters) which refuses a patient from taking part in the study according to the opinion of the investigator

Primary outcomes:
measure: Common toxicity criteria for diarrhea Version 4.0
timeFrame: Baseline vs. week 12
Secondary outcomes:
measure: Quality of life by SF-12 questionnaire
timeFrame: Baseline vs. week 12
measure: Quality of life by FACIT-D questionnaire
timeFrame: Baseline vs. week 12
measure: stool consistency by Bristol stool scale
timeFrame: Baseline vs. week 12
measure: Body mass index in kg/m^2
timeFrame: Baseline vs. week 12
measure: Phase angle
timeFrame: Baseline vs. week 12
measure: C-reactive protein
timeFrame: Baseline vs. week 12
measure: Hematocrit
timeFrame: Baseline vs. week 12
measure: alpha-1-Antitrypsin
timeFrame: Baseline vs. week 12
measure: Calprotectin
timeFrame: Baseline vs. week 12
measure: Body cell mass in kg
timeFrame: Baseline vs. week 12
measure: ECM/BCM-Index
timeFrame: Baseline vs. week 12
Other outcomes:
measure: stool water content
timeFrame: Baseline vs. week 12
measure: stool microbiome analyses
timeFrame: Baseline vs. week 12
Locations:
city: Ludwigsburg
country: Germany
facility: Klinikum Ludwigsburg
state: Baden-Württemberg
city: Ostfildern
country: Germany
facility: Paracelsus-Krankenhaus Ruit
state: Baden-Württemberg
city: Reutlingen
country: Germany
facility: Klinikum am Steinenberg /Ermstalklinik
state: Baden-Württemberg
city: Stuttgart
country: Germany
facility: Klinikum Stuttgart
state: Baden-Württemberg
city: Stuttgart
country: Germany
facility: Klinikum Stuttgart
state: Baden-Württemberg
Study officials:
affiliation: ZKES GmbH
name: Stephan C. Bischoff, Prof.
role: STUDY_DIRECTOR
References: