Effects of a Probiotic Intervention on the Gut and Vaginal Microbiome in Patients With Advanced or Recurrent Ovarian Cancer Undergoing Treatment With Platinum Chemotherapy

A Randomized, Double-Blind, Placebo Controlled, Study to Investigate Efficacy of a Probiotic Intervention on the Gut and Vaginal Microbiome of Ovarian Cancer Patients Undergoing Treatment With Platinum Chemotherapy

This clinical trial evaluates the effects a probiotic intervention has on the gut and vaginal microbiome in patients undergoing chemotherapy for ovarian cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has come back after a period of improvement (recurrent). Gut health is also known as the gut microbiome. The microbiome includes all of the bacteria and organisms naturally found in the digestive tract. Probiotics are dietary supplements containing live microorganisms that may help keep the gastrointestinal tract healthy. A probiotic intervention during platinum chemotherapy in ovarian cancer patients may impact the gut and vaginal microbiota, quality of life, symptoms, and oncologic outcomes.

PRIMARY OBJECTIVE:

I. To evaluate changes to the gut microbiome composition in ovarian cancer patients randomized to a probiotic intervention versus placebo during platinum chemotherapy.

SECONDARY OBJECTIVES:

I. Compliance with probiotic intervention in ovarian cancer patients during chemotherapy.

II. Compliance with gut microbiome collection in ovarian cancer patients during chemotherapy.

III. Compliance with vaginal microbiome collection in ovarian cancer patients during chemotherapy.

IV. Recurrence free survival (RFS). V. Overall survival (OS).

EXPLORATORY OBJECTIVES:

I. To evaluate changes in the vaginal microbiome composition of ovarian cancer patients randomized to a probiotic intervention versus placebo during platinum chemotherapy.

II. Assess pre-chemotherapy diet according to the Food Frequency Questionnaire (FFQ, Diet History Questionnaire [DHQ3]) questionnaire and how this influences the patient's baseline gut and vaginal microbiome.

III. Assess whether a probiotic intervention influences chemotherapy toxicity and morbidity.

IV. Assess whether a probiotic intervention influences stool consistency or need for additional medications during chemotherapy.

V. Assess impact of gut and vaginal microbiome on patient quality of life. VI. Assess changes in serum metabolomic and immune markers as a result of the probiotic intervention.

VII. Assess whether probiotic intervention is associated with chemotherapy-induced neutropenia, neutropenic fever and dose-delays.

VIII. In patients who undergo standard-of-care surgery during chemotherapy, assessment of post-operative infectious outcomes, including surgical site infection in ovarian cancer patients randomized to a probiotic intervention versus placebo during platinum chemotherapy.

IX. In patients who undergo standard-of-care surgery during chemotherapy, assessment of the tumor microbiome as a result of probiotic intervention versus placebo.

X. In patients who are treated with antibiotics as standard of care for infectious causes during chemotherapy, assess changes in the vaginal and gut microbiome related to antibiotic therapy.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive probiotic orally (PO) twice daily (BID) beginning within seven days of standard of care (SOC) platinum chemotherapy cycle 1 until seven days after their cycle 6. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood and vaginal sample collection throughout the study.

ARM II: Patients receive placebo PO BID beginning within seven days of SOC platinum chemotherapy cycle 1 until seven days after their cycle 6. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood and vaginal sample collection throughout the study.

Inclusion Criteria:

• Ability to understand and willingness to sign a written consent form. In patients who do not speak English, ability to have informed consent form translated in their native language and have their native language translator present for consenting process
• Age > 18 years old
• Patient with advanced (stage II, III or IV) or recurrent ovarian cancer who will receive platinum-based chemotherapy as standard of care (cisplatin, carboplatin containing regimens)
• Agreeable to participate in all research activities defined in the study
• Agreeable to not take any other probiotic and/or prebiotic supplements outside of study intervention during the study
• Agreeable to not make significant changes to their diet throughout the course of the study
• Patients with ileostomy, colostomy are permitted to participate

Exclusion Criteria:

• Borderline ovarian tumors
• Prior allergy or food intolerance to any probiotic product
• History of chronic inflammation or active structural abnormality of the digestive tract (e.g., inflammatory bowel disease requiring medications, active duodenal or gastric ulcer, complete large or small bowel intestinal obstruction, active fistula)
• Patients who do not meet laboratory parameters for platinum-based chemotherapy, including absolute neutrophil count (ANC) < 1500
• Known hypersensitivity to any component of study product (Akkermansia muciniphila, Anaerobutyricum hallii, Clostridium beijerinckii, Clostridium butyricum and Bifidobacterium infantis, chicory inulin, magnesium stearate, grape food color, and silica)
• Known hypersensitivity to > 4 first-line antimicrobial therapies against Akkermansia muciniphila, Clostridium beijerinckii, Clostridium butyricum, Anaerobutyricum hallii: penicillin, piperacillin, tetracycline, amoxicillin, ampicillin
• Known hypersensitivity to > 4 first-line antimicrobial therapies against Bifidobacterium infantis Bi-26^Trademark (TM): gentamicin, kanamycin, streptomycin, tetracycline, erythromycin, clindamycin, ampicillin, vancomycin