VSL#3 Versus Placebo in Increasing the Pathological Major Response Rate in Patients With Rectal Cancer

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled phase III study involving 160 patients designed to assess the efficacy of the high potency probiotic preparation VSL#3® versus placebo in increasing the pathological major response rate in patients undergoing concurrent CT and pelvic RT.

Official Title
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A Phase III, Randomized, Double-Blind Placebo Controlled Study of the Probiotic Preparation VSL#3® Versus Placebo in Increasing the Pathological Major Response Rate in Patients Receiving Concurrent Chemotherapy and Pelvic Radiation Therapy

Conditions
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Rectal Cancer

Intervention / Treatment
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* Other: VSL#3
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years Ability to sign informed consent and understand the nature of a placebo- controlled trial. Ability to complete questionnaire(s) by themselves or with assistance. Life expectancy ≥ 6 months. Current diagnosis of cancer that supports the use of continuous definitive or adjuvant external-beam RT to the pelvis to a minimum dose of 4500 cGy delivered with conventional multi-field photon radiotherapy, 3-D conformal photon radiotherapy or intensity modulated photon therapy. Will receive concurrent administration of chemotherapy (5-FU, capecitabine, cisplatin, oxaliplatin, carboplatin, and/or mitomycin) during pelvic RT The following laboratory values obtained > 28 days prior to registration: Hemoglobin > 10.0 g/dL WBC > 3,500 Absolute neutrophil count > 1,500 Platelets > 100,000 ECOG Performance Status (PS) of 0, 1 or 2 Willing to abstain from ingestion of yogurt products and/or any product containing probiotics during study drug treatment. Exclusion Criteria: Current or prior metastases beyond regional lymph nodes. Undergone abdominal-perineal resection, Hartmann procedure, or other surgical procedure leaving the patient without a functioning rectum. Known allergy to a probiotic preparation. Any history of inflammatory bowel disease. -> grade 3 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. Planned use of leucovorin (because of the risk of secretory diarrhea). Split-course RT is planned. Prior pelvic RT. Proton RT. Any of the following: Pregnant women Nursing women Men or women of childbearing potential who are unwilling to employ adequate contraception Use of probiotics ≤ 2 weeks prior to registration. Use of antibiotics ≤ 1 week prior to registration. Planned continuous antibiotic treatment during RT. History of gastrointestinal or genitourinary obstruction or porphyria.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VSL#3 PROBIOTIC PREPARATION<br> | Other: VSL#3<br>* 1 sachet (4.5x1011 viable lyophilized bacteria)three times in a day, during RT and for 2 weeks before and for 4 weeks afterwards.<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* 1 sachet, three times in a day, during RT and for 2 weeks before and for 4 weeks afterwards<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The impact of the probiotic preparation on increasing the TRG1-2 rate. |  | From the date of randomization until to the date of surgery, up to 18 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine whether VSL#3® can have an impact on reduction of acute bowel toxicity |  | 12-36 months | 
| pathological complete response (pCR) |  | 12-36 months | 
| impact on reduction of sphincter saving surgery (SSS) |  | 12-36 months | 
| disease free survival (DFS) at 36 months |  | 36 months | 
| Determine whether VSL#3® can have an impact on reduction of late toxicity at 12 and 36 months. |  | 12, 36 months |