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

Gastrointestinal Neoplasms Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01790035
• Other study ID #: 201404101
• Status: Terminated
• Phase: Phase 1
• Start date: August 19, 2014
• Est. completion date: December 12, 2021

Study information

• Verified date: March 2022
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 23
• Est. completion date: December 12, 2021
• Est. primary completion date: January 12, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Digestive System Neoplasms
• Gastrointestinal Neoplasms

Intervention

Drug:
• LGG

• Placebo

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View 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. — View 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. Review. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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.	Up to 5 years after completion of treatment.
Secondary	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)	Up to 2 weeks after completion of treatment
Secondary	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	Up to 6 months following the last dose of LGG or placebo
Secondary	Fecal calprotectin	Determine whether fecal calprotectin correlates with onset, duration, and/or severity of diarrhea during chemoradiation	Up to 2 weeks following the completion of treatment
Secondary	Serum citrulline	Determine whether serum citrulline correlates with onset, duration, and/or severity of diarrhea during chemoradiation	Up to 2 weeks following the completion of treatment

External Links

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