Probiotic Therapy in Preventing Gastrointestinal Complications in Patients Undergoing Chemotherapy and Pelvic Radiation Therapy

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Probiotic therapy may reduce or prevent gastrointestinal complications in patients undergoing chemotherapy and pelvic radiation therapy. PURPOSE: This randomized phase III trial is studying how well probiotic therapy works in preventing gastrointestinal complications in patients undergoing chemotherapy and pelvic radiation therapy.

Detailed Description
-----------------
OBJECTIVES: Primary To determine whether live freeze-dried lactic acid bacteria probiotic (VSL#3®) is effective in reducing the acute treatment-related bowel function disturbances, as measured by the FACIT-D diarrhea subscale score in patients receiving concurrent chemotherapy and pelvic RT as adjuvant or primary treatment for malignancy. Secondary To determine whether VSL#3® can reduce chronic treatment-related bowel dysfunction following completion of therapy. To examine whether VSL#3® appears to have an impact on disease-free survival. To bank blood products for future studies. (exploratory) To characterize changes in the fecal microbiota and examine for correlation with treatment assignment and symptom scores. (exploratory) OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to site of primary tumor (rectum/anus vs other), history of anterior resection of the rectum (yes vs no), total planned cumulative dose (including boost of external-beam radiotherapy [RT] or brachytherapy) (4,500-5,350 cGy vs > 5,350 cGy), and use of intensity-modulated RT [IMRT] for pelvic RT (yes vs no). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive live freeze-dried lactic acid bacteria probiotic (VSL#3®) orally (PO) 3 times a day during RT (5-8 weeks) and for 2 weeks after completion of RT. Arm II: Patients receive placebo PO 3 times a day during RT (5-8 weeks) and for 2 weeks after completion of RT. Patients self-report symptoms using the FACIT-D, PBFQ, PRO-CTCAE, and Uniscale/fatigue weekly during RT, for 2 weeks after completion of RT, and at 12 months following the completion of RT. Blood and stool samples may be collected from some patients for correlative studies.

Official Title
-----------------
A Phase III, Randomized, Double-Blind Placebo Controlled Study of the Probiotic Preparation VSL#3® Versus Placebo in the Prevention of Acute Enteritis in Patients Receiving Concurrent Chemotherapy and Pelvic Radiation Therapy

Conditions
-----------------
Cognitive/Functional Effects, Constipation, Impaction, and Bowel Obstruction, Diarrhea, Fatigue, Gastrointestinal Complications, Psychosocial Effects of Cancer and Its Treatment, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
-----------------
* Dietary Supplement: live freeze-dried lactic acid bacteria probiotic
* Other: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Current diagnosis of cancer that supports the use of continuous definitive or adjuvant external-beam radiotherapy (RT) to the pelvis to a minimum dose of 4,500 cGy with the following parameters: The pelvis must be encompassed by the planned RT fields The superior border may not lie inferior to the most inferior aspect of the sacroiliac joints Portions of the rectum may have special blocking, depending upon disease site The total prescription dose must lie between 4,500-5,350 cGy (inclusive) A boost to primary tumor or tumor bed may be planned Planned treatment is to be given 4-5 times per week on a one- treatment-per-day basis The daily prescribed dose must lie between 170-210 cGy (inclusive) per day No planned split-course RT No proton RT Will receive concurrent administration of chemotherapy (fluorouracil, capecitabine, cisplatin, oxaliplatin, carboplatin, and/or mitomycin C) during pelvic RT No current or prior metastases beyond regional lymph nodes PATIENT CHARACTERISTICS: ECOG performance status (PS) of 0, 1, or 2 Life expectancy ≥ 6 months Able to complete questionnaire(s) by themselves or with assistance Not pregnant or nursing Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only Fertile patients must use effective contraception Hemoglobin > 10.0 g/dL White blood cells (WBC) > 3,500/mm³ Absolute neutrophil count (ANC) > 1,500/mm³ Platelet count > 100,000/mm³ Willing to abstain from ingestion of yogurt products and/or any product containing probiotics during study drug treatment No known allergy to a probiotic preparation No history of inflammatory bowel disease No ≥ grade 3 diarrhea, ≥ grade 3 rectal bleeding, abdominal cramping, or incontinence of stool ≤ 7 days prior to registration No medical condition that may interfere with ability to receive protocol treatment No history of gastrointestinal or genitourinary obstruction or porphyria No history of irritable bowel syndrome (IBS) PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior abdominal-perineal resection, Hartmann procedure, or other surgical procedure leaving the patient without a functioning rectum No planned use of leucovorin No prior pelvic RT No use of probiotics ≤ 2 weeks prior to registration No use of antibiotics ≤ 3 days prior to registration No planned continuous antibiotic treatment during RT

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive live freeze-dried lactic acid bacteria probiotic (VSL#3®) orally (PO) 3 times a day during RT (5-8 weeks) and for 2 weeks after completion of RT. | Dietary Supplement: live freeze-dried lactic acid bacteria probiotic<br>* Given orally (PO)<br>|
| Placebo Comparator: Arm II<br>Patients receive placebo PO 3 times a day during RT (5-8 weeks) and for 2 weeks after completion of RT. | Other: placebo<br>* Given PO<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average area under the curve (AUC) of the FACIT-D diarrhea subscale score assessed weekly during treatment and for two weeks following the completion of RT |  | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bowel function measures as assessed by the clinician using the CTCAE version 4 and as assessed by the PBFQ and the PRO-CTCAE |  | Up to 12 months | 
| Psychometric evaluation of the reliability and validity of the FACIT-D diarrhea subscale, PBFQ, and PRO-CTCAE |  | Up to 12 months | 
| Disease-free survival |  | Up to 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
diarrhea, constipation, impaction, and bowel obstruction, gastrointestinal complications, fatigue, psychosocial effects of cancer and its treatment, cognitive/functional effects, unspecified adult solid tumor, protocol specific