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

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.

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