5-strain Probiotic Formulation in HR-positive Breast Cancer Receiving Aromatase Inhibitor to Prevent Bone Loss

PRIMARY OBJECTIVE:

I. To evaluate the median percent change from baseline (prior to the start of an aromatase inhibitor [AI]) at 15 months in C-terminal telopeptide of type 1 collagen (CTx) in early-stage breast cancer patients who receive WBF-038 treatment for 12 months starting at 3 months post-baseline.

SECONDARY OBJECTIVES:

I. To evaluate the median percent change from baseline (prior to the start of an AI) at 15 months in the lumbar spine and hip bone mineral density in early-stage breast cancer patients who receive WBF-038 treatment for 12 months starting at 3 months post-baseline.

II. To evaluate safety and risk of fracture associated with WBF-038.

EXPLORATORY OBJECTIVES:

I. To evaluate changes from baseline (prior to the start of an AI) over time in CTx, alkaline phosphatase (ALK), fasting blood sugar (FBS), hemoglobin A1C (HbA1C), and Procollagen I Intact N-Terminal (P1NP) at 3, 6, 15, and 18 months post-baseline.

II. To evaluate changes from baseline (prior to the start of an AI) over time in weight and waist circumference at 3, 6, 15, and 18 months post-baseline.

III. To evaluate changes in the cytokine profile over time. IV. To evaluate the association between stool microbiome, stool short-chain fatty acid (SCFA), and serum SCFA and changes over time in CTx and lumbar spine and hip bone mineral density.

V. To evaluate changes over time in AI-associated musculoskeletal symptoms (AIMSS) with patient-reported outcomes (PRO) using the Stanford Health Assessment Questionnaire (HAQ) and pain visual analog scale (VAS).

OUTLINE:

Patients receive WBF-038 orally (PO) once daily (QD) for 365 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and bone mineral density (BMD) test at screening and on study.

After completion of study intervention, patients are followed up at 90 days.

Inclusion criteria

• Female age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
• Histologically confirmed anatomical stage 0-III hormone receptor-positive breast cancer
• Will be starting on an aromatase inhibitor (letrozole, anastrozole, or exemestane) ± ovarian function suppression (OFS) per treating physician's discretion
• Absolute neutrophil count (ANC) ≥ 1000/mm^3 (prior to registration)
• Platelet count ≥ 75,000/mm^3 (prior to registration)
• Hemoglobin ≥ 9.0 g/dL (prior to registration)
• Creatinine ≤ 2 x upper limit of normal (ULN) (prior to registration)
• Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) ≤ 2 x ULN (prior to registration)
• Albumin ≥ 3 g/dL (prior to registration)
• Willing and able to provide research stool and blood samples
• Negative serum pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only (< 60 years old with intact uterus)
• Capable of providing valid informed consent
• Willing to return to enrolling institution for all study visits (blood draws, etc)

Exclusion criteria

• Requires prolonged systemic antibiotic therapy for other conditions and recent systemic antibiotic ≤ 14 days prior to registration
• Fecal microbiota transplant (FMT) ≤ 6 months prior to registration
• FMT with an associated serious adverse event related to the FMT product or procedure
• Co-morbid systemic illnesses or other severe concurrent diseases which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of over-the-counter probiotics
• Immunocompromised patients including patients known to be HIV positive or those on chronic steroids > 20 mg prednisone a day or prednisone-equivalent. Note: Must be off systemic steroids ≥ 90 days prior to registration. However, topical steroids, inhalants, or steroid eye drops are permitted
• History of inflammatory bowel disease (IBD), e.g., ulcerative colitis, Crohn's disease, or microscopic colitis
• History of chronic diarrhea
• History of celiac disease
• Currently has a colostomy
• Intraabdominal surgery related to gastrointestinal tract ≤ 60 days prior to registration
• Evidence of active, severe colitis
• History of short gut syndrome or motility disorders
• Requires the daily use of medications to manage bowel hypermotility, such as imodium or lomotil
• Active autoimmune disease that has required systemic treatment in the ≤ 30 days (i.e., with the use of disease-modifying agents, corticosteroids, or immunosuppressive products) prior to registration. Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment ≤ 30 days prior to registration are not excluded
• History of osteoporosis or hyperparathyroidism
• History of untreated vitamin D deficiency
• Receiving or will receive bisphosphonates during study period (alendronate, risedronate, ibandronate, pamidronate, or zolendronic acid) or denosumab
• Patients who received oral bisphosphonate within ≤ 12 weeks, intravenous (IV) zoledronic acid (Reclast) ≤ 52 weeks, or denosumab ≤ 24 weeks will also be excluded
• Known hypersensitivity to any component of study product (including known inulin intolerance)
• Known hypersensitivity to > 4 first-line antimicrobial therapies against akkermansia muciniphila, clostridium beijerinckii, clostridium butyricum, anaerobutyricum hallii, including penicillin, piperacillin, tetracycline, amoxicillin, or ampicillin
• Known hypersensitivity to > 4 first line antimicrobial therapies against bifidobacterium infantis Bi-26TM, including gentamicin, kanamycin, streptomycin, tetracycline, erythromycin, clindamycin, ampicillin, vancomycin
• Received an experimental product ≤ 30 days prior to registration
• Receiving or will receive CDK 4/6 inhibitor (abemaciclib, ribociclib, or palbociclib)
• Received chemotherapy ≤ 30 days prior to registration