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

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

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.

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.