Clinical trial NCT01473290: Probiotic Therapy in Preventing Gastrointestinal Complications in Patients Undergoing Chemotherapy and Pelvic Radiation Therapy
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
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
Keywords: 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
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2011-11-17
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: 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
timeFrame: Up to 12 months
Secondary outcomes:
measure: Bowel function measures as assessed by the clinician using the CTCAE version 4 and as assessed by the PBFQ and the PRO-CTCAE
timeFrame: Up to 12 months
measure: Psychometric evaluation of the reliability and validity of the FACIT-D diarrhea subscale, PBFQ, and PRO-CTCAE
timeFrame: Up to 12 months
measure: Disease-free survival
timeFrame: Up to 12 months
Other outcomes:
Locations:
Study officials:
affiliation: Mayo Clinic
name: Robert C. Miller, MD
role: PRINCIPAL_INVESTIGATOR
References: