Probiotic Supplementation in Preventing Treatment-Related Diarrhea in Patients With Cancer Undergoing Chemotherapy

A Phase II Feasibility and Correlative Study of Probiotic Supplementation in Cancer Patients Receiving Chemotherapy or Tyrosine Kinase Inhibitors (TKIs)

This randomized phase II clinical trial studies probiotic supplementation in preventing treatment-related diarrhea in patients with cancer undergoing chemotherapy. Probiotics may help prevent diarrhea caused by treatment with chemotherapy.

Study Overview

• Status: Withdrawn
• Conditions: Diarrhea; Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: questionnaire administration; Procedure: quality-of-life assessment; Dietary supplement: placebo; Dietary supplement: Lactobacillus plantarum strain 299v; Dietary supplement: Lactobacillus acidophilus probiotic; Dietary supplement: Bifidobacterium lactis probiotic supplement

Detailed Description

PRIMARY OBJECTIVES:

I. Incidence of moderate/severe (grade 2-4) diarrhea graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

II. Functional Assessment of Chronic Illness Therapy - Diarrhea (FACIT-D) Trial Outcome Index.

SECONDARY OBJECTIVES:

I. To evaluate the effects of probiotic supplementation on dose delays or reductions due to gastrointestinal (GI) toxicity.

II. To evaluate the effects of probiotic supplementation on anti-diarrheal medication use.

III. To evaluate the effects of probiotic supplementation on overall health-related quality of life (HR-QOL).

IV. To evaluate the effects of probiotic supplementation on febrile neutropenia.

V. To evaluate the effects of probiotic supplementation on adverse GI effects. VI. To evaluate the effects of probiotic supplementation on overall survival. VII. To evaluate the effects of probiotic supplementation on progression free survival.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive a mixture of Lactobacillus plantarum strain 299v, Bifidobacterium lactis probiotic supplement, and Lactobacillus acidophilus probiotic orally (PO) twice daily (BID) for 9 weeks. Treatment continues in the absence of unacceptable toxicity.

ARM II: Patients receive placebo PO BID 9 weeks. Treatment continues in the absence of unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks and then every 3 months.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University

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

Inclusion Criteria:

• Any patient with a documented malignancy initiating treatment including (as a single agent or in combination with other drugs) any one of the following cancer therapeutics:

  o Fluorouracil (5FU), capecitabine, irinotecan, paclitaxel, docetaxel, cabazitaxel, crizotinib, sorafenib, sunitinib, erlotinib, or lapatinib

• Any pathologically confirmed malignancy for which the patient would receive any of the listed cancer therapeutics
• Performance status of Eastern Cooperative Oncology Group (ECOG) 0-2
• Patient must have an estimated life expectancy of at least 6 months
• Absolute neutrophil count (ANC) > 1500
• Platelets > 100K
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 x ULN (upper limit normal)
• Serum bilirubin < 1.5 x ULN
• Serum creatinine < 1.5 x ULN
• Ability to understand and the willingness to sign a written informed consent document and comply with the treatment protocol

Exclusion Criteria:

• Patients currently undergoing treatment with the above listed therapeutics at time of initiation of trial; patients can have had prior treatment(s) with one or more of the agents if they are initiating a new treatment with another agent on the list, provided they have had at least a 2 week "washout" period
• Patients currently taking anti-diarrheal medications or therapy
• Patients undergoing hemodialysis
• Patients with known allergic or hypersensitivity reaction to probiotics, yoghurt, or similar diet or supplemental products
• Acute or chronic diarrhea, including lactose intolerance, gluten or other dietary sensitivity resulting in gastrointestinal symptoms
• Pregnant or nursing patients
• Known human immunodeficiency virus (HIV) positive
• Prior abdominal surgery resulting in a stoma, ostomy, fistula, or other anatomic defect
• Concurrent or near future radiotherapy; prior, completed radiotherapy allowed; any radiotherapy within the vicinity of the GI tract must have been completed at least 4 weeks prior to start of trial
• Treatment with any investigational drug within 4 weeks prior to enrollment
• Current treatment with antibiotics or other gut motility agents within 2 weeks of starting study medication
• Abnormal thyroid function that is not controlled with medication
• Patients taking other dietary supplements within 2 weeks of starting study medication
• Any other serious or uncontrolled illness which, in the opinion of the investigator, makes it undesirable for the patient to enter the trial

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 (probiotic mix); Patients receive a mixture of Lactobacillus plantarum strain 299v, Bifidobacterium lactis probiotic supplement, and Lactobacillus acidophilus probiotic PO BID for 9 weeks. Treatment continues in the absence of unacceptable toxicity.	Other: laboratory biomarker analysis; Correlative studies; Other: questionnaire administration; Ancillary studies; Procedure: quality-of-life assessment; Ancillary studies; Other Names: quality of life assessment; Dietary supplement: Lactobacillus plantarum strain 299v; Given PO; Other Names: Lp 299v; DSM 9843; Dietary supplement: Lactobacillus acidophilus probiotic; Given PO; Dietary supplement: Bifidobacterium lactis probiotic supplement; Given PO
Placebo Comparator: Arm II (placebo); Patients receive placebo PO BID 9 weeks. Treatment continues in the absence of unacceptable toxicity.	Other: laboratory biomarker analysis; Correlative studies; Other: questionnaire administration; Ancillary studies; Procedure: quality-of-life assessment; Ancillary studies; Other Names: quality of life assessment; Dietary supplement: placebo; Given PO; Other Names: PLCB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of grade 2-4 diarrhea over the 9-week study period, assessed by CTCAE version 4.0	Will be calculated by the percentage of patients experiencing grade 2-4 diarrhea as documented by patient diary and primary oncologist's documentation. The data for patients on tyrosine kinase inhibitors and conventional cytotoxic chemotherapy will be analyzed both combined and separately.	Up to 9 weeks
FACIT-D Trial Outcome Index (TOI)	The FACIT-D TOI has a range of scores from 0-100 which are a combination of physical well being, functional well being, and diarrhea subscale. The data for patients on tyrosine kinase inhibitors and conventional cytotoxic chemotherapy will be analyzed both combined and separately.	Up to 4 weeks post treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression free survival	Up to 2 years
Overall survival	Up to 2 years
Dose delays or reductions due to GI toxicity	Up to 9 weeks
Anti-diarrheal use	Up to 9 weeks
Overall HR-QOL	Up to 4 weeks post treatment
Febrile neutropenia	Up to 4 weeks post treatment
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	Up to 4 weeks post treatment

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Russell Pachynski, Stanford University

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Anticipated): September 1, 2014

Study Registration Dates

• First Submitted: July 12, 2012
• First Submitted That Met QC Criteria: July 17, 2012
• First Posted (Estimate): July 18, 2012

Study Record Updates

• Last Update Posted (Estimate): February 14, 2014
• Last Update Submitted That Met QC Criteria: February 12, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: Quality of Life
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Diarrhea
• Other Study ID Numbers: VAR0084; NCI-2012-01127 (Registry Identifier: CTRP (Clinical Trial Reporting Program))