Lactobacillus Rhamnosus in Prevention of Chemotherapy-related Diarrhoea

November 22, 2021 updated by: Heikki Joensuu, University of Helsinki

Randomized, Double Blind, Placebo Controlled, Cross-over Phase II Study on the Effects of Lactobacillus Rhamnosus GG Supplementation in Patients on 1st Line XELOXA Treatment for Metastatic Colorectal Cancer

Chemotherapy may cause diarrhoea, which may be associated with treatment delay and infections. The purpose of the study is to investigate whether oral supplementation with lactobacilli will alleviate chemotherapy related diarrhoea. Patients diagnosed with advanced colorectal cancer and who will receive chemotherapy will be randomly assigned to receive either lactobacilli or placebo during chemotherapy. The study is a prospective, multicenter, randomized, double-blind, placebo-controlled study. The primary outcome measure is frequency of moderate/severe diarrhoea. The study will also address safety and tolerability of chemotherapy, response to chemotherapy, and serum growth factor levels.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a prospective, multicenter, randomized, cross-over, double-blind, placebo-controlled study. Patients diagnosed with advanced colorectal cancer with overt distant metastases and who will receive chemotherapy consisting of capecitabine, oxaliplatin and bevacizumab, given as 3-weekly cycles, will be randomly assigned to receive either lactobacilli (GefilusR) or placebo during the first 3 cycles of chemotherapy (for 9 weeks). Following this, the groups will be crossed over and those study participants who were allocated to lactobacilli will receive placebo for 9 weeks, and vice versa. Lactobacilli and placebo are administered twice daily. The total daily dose of lactobacilli is 20 billion CFU. The primary outcome measure is frequency of moderate/severe diarrhoea (grade 2-4). Adverse effects (including the frequency of diarrhoea, flatulence, bloating, constipation, and nausea) will be longitudinally monitored based on a patient diary and study visits. The study will also address safety and tolerability of chemotherapy, response to chemotherapy, progression-free survival, resectability of liver metastases, and serum growth factor levels. A total of 84 patients are planned to be entered.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
84

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Finland
      • Helsinki, Finland, FIN-00029
        • Department of Oncology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with histologically confirmed diagnosis of CRC, chemotherapy naïve for metastatic disease (prior adjuvant chemotherapy for CRC allowed), who are scheduled to start capecitabine treatment as first line chemotherapy for metastatic disease
  • Age 18 or older
  • Measurable or non-measurable metastatic disease
  • Performance status ECOG performance status 0-2
  • Life expectancy greater than 3 months
  • Thrombocytes 100,000/µL or greater, neutrophils 1.500/µl or greater, Aspartate amino transferase/Alanine amino transferase <= 2.5 x Upper limit of normal (ULN) (< 5 x ULN if liver metastases present), Alkaline phosphatase <=2.5 x ULN (< 5 x ULN if liver metastases present), Serum bilirubin <= 1.5 x ULN, Serum Creatinine <= 1.5 x ULN, Urine dipstick of proteinuria <2+ (or U-Prot <100mg/dl). Patients discovered to have 2+ or greater proteinuria on dipstick urinalysis at baseline, must undergo a 24-hour urine collection and must have <= 1 g of protein/24 hr
  • Women of childbearing potential must have a negative serum pregnancy test done prior to the administration of bevacizumab. Patient and their partner should prevent pregnancy (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) up to at least 6 months after last treatment completion or the last drug dose, whatever happens first
  • Signed written informed consent according to ICH/GCP and the local regulations (approved by the Independent Ethics Committee [IEC]) will be obtained prior to any study specific screening procedures
  • Patient must be able to comply with the protocol

Exclusion Criteria:

  • Prior treatment with first-line chemotherapy for metastatic CRC
  • Adjuvant treatment with bevacizumab within 12 months
  • Acute or chronic diarrhea or colostomy
  • Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 0 (Patients must have recovered from any major surgery)
  • Near future planned radiotherapy for underlying disease (prior completed radiotherapy treatment allowed)
  • Clinical or radiological evidence of CNS metastases
  • Past or current history within the last 5 years of malignancies except for the indication under this study and curatively treated Basal and squamous cell carcinoma of the skin or In-situ carcinoma of the cervix
  • Serious non-healing wound or ulcer
  • Evidence of bleeding diathesis or coagulopathy
  • Uncontrolled hypertension
  • Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤ 6 months), myocardial infarction (≤ 6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication
  • Treatment with any investigational drug (including IMMP, EGFR inhibitors) or participation in another investigational study within 30 days prior to enrolment
  • Evidence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the treatment or patient at high risk from treatment complications
  • Ongoing treatment with aspirin (> 325 mg/day), continuous high dose NSAIDS or other medications known to predispose to gastrointestinal ulceration
  • Pregnancy (positive serum pregnancy test) and lactation
  • Any other serious or uncontrolled illness which, in the opinion of the investigator, makes it undesirable for the patient to enter the trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Lactophilus
Lactophilus supplementation
Dietary supplement: Lactobacillus Rhamnosus supplementation
Lactophilus supplementation is administered during chemotherapy.
Other Names:
  • Probiotics
Placebo Comparator: Placebo
Placebo is administered during chemotherapy.
Dietary supplement: Lactobacillus Rhamnosus supplementation
Lactophilus supplementation is administered during chemotherapy.
Other Names:
  • Probiotics
Other: Placebo administration.
Placebo is administered during chemotherapy.
Other Names:
  • Placebo.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Effect on the treatment-related grade 2 to 4 diarrhoea
Time Frame: 18 weeks
Numbers of bowel movements per day.
18 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Effect on treatment related toxicity other than diarrhea
Time Frame: 18 weeks
Adverse effects detected in the study groups.
18 weeks
Association between supplementation and response
Time Frame: 18 weeks
Response rate assessed with imaging.
18 weeks
Effect on resectability of liver metastases
Time Frame: 1 year
Numbers of liver resections carried out.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Helsinki

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Helsinki University Central Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Heikki Joensuu, M.D., Department of Oncology, Helsinki University Central Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2005

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 30, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 12, 2005

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 12, 2005

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 20, 2005

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 24, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 22, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ML18581

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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