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Probiotic LGG for Prevention of Side Effects in Patients Undergoing Chemoradiation for Gastrointestinal Cancer (LGG)

Primary Purpose

Gastrointestinal Neoplasms

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
LGG
Placebo
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastrointestinal Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Current diagnosis of a gastrointestinal, abdominal, or pelvic cancer for which the use of continuous definitive or adjuvant external-beam RT to the abdomen or pelvis to a minimum dose of 4500 cGy is planned.
  • Scheduled to receive concurrent administration of fluoropyrimidine chemotherapy (5-FU or capecitabine) during radiation therapy.
  • Age ≥ 18 years.
  • Life expectancy ≥ 6 months.
  • Negative pregnancy test done ≤7 days prior to registration (for women of childbearing potential only).

  • The following laboratory values obtained ≤ 28 days prior to registration:

    • Hemoglobin ≥ 9.0 g/dL
    • WBC ≥ 3,500
    • Absolute neutrophil count ≥ 1,500
    • Platelets ≥ 100,000
  • ECOG Performance Status (PS) of 0, 1, or 2.
  • Willingness to abstain from ingestion of yogurt products and/or any product containing probiotics during study drug treatment.
  • Ability to complete questionnaire(s) alone or with assistance.
  • Ability to understand and willingness to sign informed consent.

Exclusion Criteria:

  • Previous bowel resection which, in the opinion of the investigator, would decrease the benefit of the probiotic. Patients who have undergone recent bowel surgeries which would not decrease the benefit of the probiotic are eligible provided they are more than 30 days from surgery with no serious complications.
  • Known allergy to a probiotic preparation.
  • Any history of inflammatory bowel disease.
  • Grade 3 or 4 diarrhea, rectal bleeding, abdominal cramping, or incontinence of stool ≤7 days prior to registration.
  • Any medical condition that may interfere with ability to receive protocol treatment.
  • Prior abdominal or pelvic RT.
  • Use of probiotics ≤ 2 weeks prior to registration.
  • Use of antibiotics ≤ 3 days prior to registration.
  • Planned continuous antibiotic treatment during RT.
  • History of gastrointestinal or genitourinary obstruction or porphyria.
  • History of irritable bowel syndrome (IBS).
  • History of hypersensitivity to all of the following antibiotics: penicillin, erythromycin, clindamycin, and any fluoroquinolone.

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

No Intervention

Arm Label

LGG

Placebo

No intervention

Arm Description

LGG (containing 10^10 viable bacteria) taken by mouth twice daily beginning at baseline (but starting at least 3 days prior to the start of radiation) and continue during RT and for the 2 weeks following RT.

Placebo taken by mouth twice daily beginning at baseline (but starting at least 3 days prior to the start of radiation) and continue during RT and for the 2 weeks following RT.

Patients who prefer not to receive LGG will not be randomized and will receive standard of care RT. These patients will serve as a non-intervention comparator cohort to the first 20 patients and will have specimens collected but will not receive the placebo.

Outcomes

Primary Outcome Measures

Efficacy (randomized phase II trial)
Compare the proportion of patients receiving abdominal or pelvic chemoradiation with a fluoropyrimidine being treated with the probiotic LGG who develop CTCAE grade 2 or greater diarrhea to the proportion of patients receiving abdominal or pelvic chemoradiation with a fluoropyrimidine being treated with placebo who develop CTCAE grade 2 or greater diarrhea
Safety (phase I safety lead-in)
Determine the safety and tolerability of LGG in patients receiving abdominal or pelvic chemoradiation with a fluoropyrimidine The DSMC will review the data as part of an interim analysis when the last patient has had 30 days of follow-up. The DSMC will ensure that at least 18 patients have had follow-up at 30 days (with expected 10% drop-out). Accrual to the randomized portion of the trial will occur only if there are no episodes of lactobacillus associated septicemia. Additionally, if two or more serious adverse events of a similar nature occur and a causal relationship to the investigational product cannot be excluded, accrual to the randomized portion will not occur.

Secondary Outcome Measures

Diarrhea subscale score
The average AUC of the FACIT-D diarrhea subscale scores will be compared between the two treatment groups using a two-sample t-test. The FACIT-D will be completed at baseline, weekly during radiation treatment, for the two weeks following completion of radiation treatment, 12 months following the end of radiation treatment, and years 2-5 following the completion of radiation treatment.
Need for antidiarrhea medication
Need for use of an antidiarrheal medication (Loperamide) will be evaluated at a binary endpoint (Use or No Use). Comparison will be made using Fisher's exact test as previously described (Chitapanarux 2010)
Grade 3 or greater diarrhea
In patients receiving abdominal or pelvic chemoradiation with a fluoropyrimidine, compare the proportion of patients who develop diarrhea of grade 3 or greater (by CTCAE version 4.0) in those treated with the probiotic LGG to the proportion in those receiving placebo
Fecal calprotectin
Determine whether fecal calprotectin correlates with onset, duration, and/or severity of diarrhea during chemoradiation
Serum citrulline
Determine whether serum citrulline correlates with onset, duration, and/or severity of diarrhea during chemoradiation

Full Information

First Posted
February 8, 2013
Last Updated
March 1, 2022
Sponsor
Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT01790035
Brief Title
Probiotic LGG for Prevention of Side Effects in Patients Undergoing Chemoradiation for Gastrointestinal Cancer
Acronym
LGG
Official Title
A Phase I and Randomized Controlled Phase II Trial of the Probiotic LGG for Prevention of Side Effects in Patients Undergoing Chemoradiation for Gastrointestinal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Terminated
Why Stopped
Low accrual
Study Start Date
August 19, 2014 (Actual)
Primary Completion Date
January 12, 2017 (Actual)
Study Completion Date
December 12, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Phase 3 placebo-controlled trial to determine efficacy of the probiotic LGG for reducing acute treatment related GI toxicity in patients with GI malignancy with phase 1 safety lead-in.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastrointestinal Neoplasms

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LGG
Arm Type
Experimental
Arm Description
LGG (containing 10^10 viable bacteria) taken by mouth twice daily beginning at baseline (but starting at least 3 days prior to the start of radiation) and continue during RT and for the 2 weeks following RT.
Arm Title
Placebo
Arm Type
Experimental
Arm Description
Placebo taken by mouth twice daily beginning at baseline (but starting at least 3 days prior to the start of radiation) and continue during RT and for the 2 weeks following RT.
Arm Title
No intervention
Arm Type
No Intervention
Arm Description
Patients who prefer not to receive LGG will not be randomized and will receive standard of care RT. These patients will serve as a non-intervention comparator cohort to the first 20 patients and will have specimens collected but will not receive the placebo.
Intervention Type
Drug
Intervention Name(s)
LGG
Other Intervention Name(s)
Culturelle
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Efficacy (randomized phase II trial)
Description
Compare the proportion of patients receiving abdominal or pelvic chemoradiation with a fluoropyrimidine being treated with the probiotic LGG who develop CTCAE grade 2 or greater diarrhea to the proportion of patients receiving abdominal or pelvic chemoradiation with a fluoropyrimidine being treated with placebo who develop CTCAE grade 2 or greater diarrhea
Time Frame
Up to 6 months following the last dose of LGG or placebo
Title
Safety (phase I safety lead-in)
Description
Determine the safety and tolerability of LGG in patients receiving abdominal or pelvic chemoradiation with a fluoropyrimidine The DSMC will review the data as part of an interim analysis when the last patient has had 30 days of follow-up. The DSMC will ensure that at least 18 patients have had follow-up at 30 days (with expected 10% drop-out). Accrual to the randomized portion of the trial will occur only if there are no episodes of lactobacillus associated septicemia. Additionally, if two or more serious adverse events of a similar nature occur and a causal relationship to the investigational product cannot be excluded, accrual to the randomized portion will not occur.
Time Frame
Up to 30 days following completion of treatment
Secondary Outcome Measure Information:
Title
Diarrhea subscale score
Description
The average AUC of the FACIT-D diarrhea subscale scores will be compared between the two treatment groups using a two-sample t-test. The FACIT-D will be completed at baseline, weekly during radiation treatment, for the two weeks following completion of radiation treatment, 12 months following the end of radiation treatment, and years 2-5 following the completion of radiation treatment.
Time Frame
Up to 5 years after completion of treatment.
Title
Need for antidiarrhea medication
Description
Need for use of an antidiarrheal medication (Loperamide) will be evaluated at a binary endpoint (Use or No Use). Comparison will be made using Fisher's exact test as previously described (Chitapanarux 2010)
Time Frame
Up to 2 weeks after completion of treatment
Title
Grade 3 or greater diarrhea
Description
In patients receiving abdominal or pelvic chemoradiation with a fluoropyrimidine, compare the proportion of patients who develop diarrhea of grade 3 or greater (by CTCAE version 4.0) in those treated with the probiotic LGG to the proportion in those receiving placebo
Time Frame
Up to 6 months following the last dose of LGG or placebo
Title
Fecal calprotectin
Description
Determine whether fecal calprotectin correlates with onset, duration, and/or severity of diarrhea during chemoradiation
Time Frame
Up to 2 weeks following the completion of treatment
Title
Serum citrulline
Description
Determine whether serum citrulline correlates with onset, duration, and/or severity of diarrhea during chemoradiation
Time Frame
Up to 2 weeks following the completion of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Current diagnosis of a gastrointestinal, abdominal, or pelvic cancer for which the use of continuous definitive or adjuvant external-beam RT to the abdomen or pelvis to a minimum dose of 4500 cGy is planned. Scheduled to receive concurrent administration of fluoropyrimidine chemotherapy (5-FU or capecitabine) during radiation therapy. Age ≥ 18 years. Life expectancy ≥ 6 months. Negative pregnancy test done ≤7 days prior to registration (for women of childbearing potential only). The following laboratory values obtained ≤ 28 days prior to registration: Hemoglobin ≥ 9.0 g/dL WBC ≥ 3,500 Absolute neutrophil count ≥ 1,500 Platelets ≥ 100,000 ECOG Performance Status (PS) of 0, 1, or 2. Willingness to abstain from ingestion of yogurt products and/or any product containing probiotics during study drug treatment. Ability to complete questionnaire(s) alone or with assistance. Ability to understand and willingness to sign informed consent. Exclusion Criteria: Previous bowel resection which, in the opinion of the investigator, would decrease the benefit of the probiotic. Patients who have undergone recent bowel surgeries which would not decrease the benefit of the probiotic are eligible provided they are more than 30 days from surgery with no serious complications. Known allergy to a probiotic preparation. Any history of inflammatory bowel disease. Grade 3 or 4 diarrhea, rectal bleeding, abdominal cramping, or incontinence of stool ≤7 days prior to registration. Any medical condition that may interfere with ability to receive protocol treatment. Prior abdominal or pelvic RT. Use of probiotics ≤ 2 weeks prior to registration. Use of antibiotics ≤ 3 days prior to registration. Planned continuous antibiotic treatment during RT. History of gastrointestinal or genitourinary obstruction or porphyria. History of irritable bowel syndrome (IBS). History of hypersensitivity to all of the following antibiotics: penicillin, erythromycin, clindamycin, and any fluoroquinolone.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthew Ciorba, M.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
20040865
Citation
Packey CD, Ciorba MA. Microbial influences on the small intestinal response to radiation injury. Curr Opin Gastroenterol. 2010 Mar;26(2):88-94. doi: 10.1097/MOG.0b013e3283361927.
Results Reference
background
PubMed Identifier
19538306
Citation
Ciorba MA, Stenson WF. Probiotic therapy in radiation-induced intestinal injury and repair. Ann N Y Acad Sci. 2009 May;1165:190-4. doi: 10.1111/j.1749-6632.2009.04029.x.
Results Reference
background
PubMed Identifier
20444243
Citation
Chitapanarux I, Chitapanarux T, Traisathit P, Kudumpee S, Tharavichitkul E, Lorvidhaya V. Randomized controlled trial of live lactobacillus acidophilus plus bifidobacterium bifidum in prophylaxis of diarrhea during radiotherapy in cervical cancer patients. Radiat Oncol. 2010 May 5;5:31. doi: 10.1186/1748-717X-5-31.
Results Reference
background
PubMed Identifier
22027478
Citation
Ciorba MA, Riehl TE, Rao MS, Moon C, Ee X, Nava GM, Walker MR, Marinshaw JM, Stappenbeck TS, Stenson WF. Lactobacillus probiotic protects intestinal epithelium from radiation injury in a TLR-2/cyclo-oxygenase-2-dependent manner. Gut. 2012 Jun;61(6):829-38. doi: 10.1136/gutjnl-2011-300367. Epub 2011 Oct 24.
Results Reference
background
PubMed Identifier
29934438
Citation
Riehl TE, Alvarado D, Ee X, Zuckerman A, Foster L, Kapoor V, Thotala D, Ciorba MA, Stenson WF. Lactobacillus rhamnosus GG protects the intestinal epithelium from radiation injury through release of lipoteichoic acid, macrophage activation and the migration of mesenchymal stem cells. Gut. 2019 Jun;68(6):1003-1013. doi: 10.1136/gutjnl-2018-316226. Epub 2018 Jun 22.
Results Reference
derived
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Learn more about this trial

Probiotic LGG for Prevention of Side Effects in Patients Undergoing Chemoradiation for Gastrointestinal Cancer

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