Gastrointestinal Neoplasms
Conditions
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.
Interventions
DRUGLGG
DRUGPlacebo
Sponsors
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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) |
| 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 |
| 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 |
| 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. |
Countries
United States
Outcome results
None listed