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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Fatigue; Diarrhea; Unspecified Adult Solid Tumor, Protocol Specific; Cognitive/Functional Effects; Psychosocial Effects of Cancer and Its Treatment; Gastrointestinal Complications; Constipation, Impaction, and Bowel Obstruction
• Intervention / Treatment: Other: placebo; Dietary supplement: live freeze-dried lactic acid bacteria probiotic

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.

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Dietary supplement: live freeze-dried lactic acid bacteria probiotic; Given orally (PO)
Placebo Comparator: Arm II; Patients receive placebo PO 3 times a day during RT (5-8 weeks) and for 2 weeks after completion of RT.	Other: placebo; Given PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Registration Dates

• First Submitted: November 15, 2011
• First Submitted That Met QC Criteria: November 15, 2011
• First Posted (Estimate): November 17, 2011

Study Record Updates

• Last Update Posted (Estimate): July 6, 2016
• Last Update Submitted That Met QC Criteria: July 1, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific; fatigue; diarrhea; cognitive/functional effects; psychosocial effects of cancer and its treatment; gastrointestinal complications; constipation, impaction, and bowel obstruction
• Additional Relevant MeSH Terms: Digestive System Diseases; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Intestinal Diseases; Fatigue; Diarrhea; Constipation; Intestinal Obstruction
• Other Study ID Numbers: NCCTG-N10CB; NCI-2011-03636 (Registry Identifier: CTRP (Clinical Trials Reporting System)); CDR0000716291 (Registry Identifier: PDQ (Physician Data Query))