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

Phase 2

Withdrawn

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

• Registration Number: NCT01644097
• Lead Sponsor: Stanford University

Brief Summary

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.

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 Timeline

• Study First Submitted: 2012-07-12
• Study First Submitted QC: 2012-07-17
• Study First Posted: 2012-07-18
• Study Start: 2012-11
• Status Verified: 2014-02
• Last Update Submitted: 2014-02-12
• Last Update Posted: 2014-02-14
• Primary Completion: 2014-09

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (probiotic mix)	Lactobacillus plantarum strain 299v	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.
Arm I (probiotic mix)	Lactobacillus acidophilus probiotic	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.
Arm I (probiotic mix)	laboratory biomarker analysis	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.
Arm I (probiotic mix)	questionnaire administration	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.
Arm I (probiotic mix)	quality-of-life assessment	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.
Arm I (probiotic mix)	Bifidobacterium lactis probiotic supplement	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.
Arm II (placebo)	placebo	Patients receive placebo PO BID 9 weeks. Treatment continues in the absence of unacceptable toxicity.
Arm II (placebo)	laboratory biomarker analysis	Patients receive placebo PO BID 9 weeks. Treatment continues in the absence of unacceptable toxicity.
Arm II (placebo)	questionnaire administration	Patients receive placebo PO BID 9 weeks. Treatment continues in the absence of unacceptable toxicity.
Arm II (placebo)	quality-of-life assessment	Patients receive placebo PO BID 9 weeks. Treatment continues in the absence of unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Incidence of grade 2-4 diarrhea over the 9-week study period, assessed by CTCAE version 4.0	Up to 9 weeks	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.
FACIT-D Trial Outcome Index (TOI)	Up to 4 weeks post treatment	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.

Secondary Outcome Measures

Name	Time	Method
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
Progression free survival	Up to 2 years

Trial Locations

Locations (1)

Stanford University; 🇺🇸 Stanford, California, United States