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

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01644097
• Other study ID #: VAR0084
• Secondary ID: NCI-2012-01127
• Status: Withdrawn
• Phase: Phase 2
• First received: July 12, 2012
• Last updated: February 12, 2014
• Start date: November 2012

Study information

• Verified date: February 2014
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Diarrhea
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Dietary Supplement:
• Lactobacillus plantarum strain 299v
Given PO
• Lactobacillus acidophilus probiotic
Given PO
• placebo
Given PO

Other:
• laboratory biomarker analysis
Correlative studies
• questionnaire administration
Ancillary studies

Procedure:
• quality-of-life assessment
Ancillary studies

Dietary Supplement:
• Bifidobacterium lactis probiotic supplement
Given PO

Locations

Country	Name	City	State
United States	Stanford University	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	Dose delays or reductions due to GI toxicity		Up to 9 weeks	No
Secondary	Anti-diarrheal use		Up to 9 weeks	No
Secondary	Overall HR-QOL		Up to 4 weeks post treatment	No
Secondary	Febrile neutropenia		Up to 4 weeks post treatment	No
Secondary	Number of Participants with Adverse Events as a Measure of Safety and Tolerability		Up to 4 weeks post treatment	Yes
Secondary	Overall survival		Up to 2 years	No
Secondary	Progression free survival		Up to 2 years	No