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

NCT01790035 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 201404101
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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.

Conditions

Gastrointestinal Neoplasms

Outcome Measures

Primary Outcomes (2)

• 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

  Up to 6 months following the last dose of LGG or placebo

• 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.

  Up to 30 days following completion of treatment

Secondary Outcomes (5)

• Diarrhea subscale score

  Up to 5 years after completion of treatment.

• Need for antidiarrhea medication

  Up to 2 weeks after completion of treatment

• Grade 3 or greater diarrhea

  Up to 6 months following the last dose of LGG or placebo

• Fecal calprotectin

  Up to 2 weeks following the completion of treatment

• Serum citrulline

  Up to 2 weeks following the completion of treatment

Study Arms (3)

LGG

EXPERIMENTAL

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.

Drug: LGG

Placebo

EXPERIMENTAL

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.

Drug: Placebo

No intervention

NO INTERVENTION

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.

Interventions

LGG DRUG

Also known as: Culturelle

LGG

Placebo DRUG

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (5)

• 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.

  PMID: 20040865 BACKGROUND

• 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.

  PMID: 19538306 BACKGROUND

• 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.

  PMID: 20444243 BACKGROUND

• 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.

  PMID: 22027478 BACKGROUND

• 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.

  PMID: 29934438 DERIVED

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Gastrointestinal Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Study Officials

• Matthew Ciorba, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2013
• First Posted: February 12, 2013
• Study Start: August 19, 2014
• Primary Completion: January 12, 2017
• Study Completion: December 12, 2021
• Last Updated: March 16, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)