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

Phase 1

Terminated

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.

Recruitment & 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.

Arm && Interventions

Group	Intervention	Description
LGG	LGG	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	Placebo	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.

Primary Outcome Measures

Name	Time	Method
Efficacy (randomized phase II trial)	Up to 6 months following the last dose of LGG or placebo	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)	Up to 30 days following completion of treatment	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

Name	Time	Method
Diarrhea subscale score	Up to 5 years after completion of treatment.	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	Up to 2 weeks after completion of treatment	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	Up to 6 months following the last dose of LGG or placebo	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	Up to 2 weeks following the completion of treatment	Determine whether fecal calprotectin correlates with onset, duration, and/or severity of diarrhea during chemoradiation
Serum citrulline	Up to 2 weeks following the completion of treatment	Determine whether serum citrulline correlates with onset, duration, and/or severity of diarrhea during chemoradiation

Locations (1): Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States