Clinical trial NCT01790035: Probiotic LGG for Prevention of Side Effects in Patients Undergoing Chemoradiation for Gastrointestinal Cancer
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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Gastrointestinal Neoplasms
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2013-02-12
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Efficacy (randomized phase II trial)
timeFrame: Up to 6 months following the last dose of LGG or placebo
measure: Safety (phase I safety lead-in)
timeFrame: Up to 30 days following completion of treatment
Secondary outcomes:
measure: Diarrhea subscale score
timeFrame: Up to 5 years after completion of treatment.
measure: Need for antidiarrhea medication
timeFrame: Up to 2 weeks after completion of treatment
measure: Grade 3 or greater diarrhea
timeFrame: Up to 6 months following the last dose of LGG or placebo
measure: Fecal calprotectin
timeFrame: Up to 2 weeks following the completion of treatment
measure: Serum citrulline
timeFrame: Up to 2 weeks following the completion of treatment
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Matthew Ciorba, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.