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

NCT ID: NCT01473290

Last Updated: 2016-07-06

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

live freeze-dried lactic acid bacteria probiotic

Intervention Type: DIETARY_SUPPLEMENT

Given orally (PO)

Arm II

Patients receive placebo PO 3 times a day during RT (5-8 weeks) and for 2 weeks after completion of RT.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: OTHER

Given PO

Interventions

live freeze-dried lactic acid bacteria probiotic

Given orally (PO)

Intervention Type: DIETARY_SUPPLEMENT

placebo

Given PO

Intervention Type: OTHER

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert C. Miller, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Other Identifiers

NCI-2011-03636

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000716291

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCCTG-N10CB

Identifier Type: -

Identifier Source: org_study_id