Epidiferphane and Taxane Chemotherapy for the Treatment of Breast Cancer

Inclusion Criteria

• Adults ≥ eighteen years of age
• Subjects on the phase I portion must either be initiating neoadjuvant chemotherapy or have a clinical diagnosis of metastatic breast cancer. Subjects on the phase II portion must have a clinical diagnosis of breast cancer of any stage and histology
• An Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 3 based on treating physician assessment
• Subjects must be about to start a new treatment regimen containing either paclitaxel given weekly, or docetaxel given every 3 weeks, or nab-paclitaxel given weekly or every 3 weeks at University of Florida (UF) Health at one of the following doses: * Paclitaxel weekly at 80-90 mg/m2 * Nab-paclitaxel weekly at 75-125 mg/m2 or every three weeks at 260 mg/m2 * Docetaxel every three weeks at 75-100 mg/m2
• Subjects must continue cancer therapy at UF Health for at least the next three months
• Subjects must not have more than one active malignancy at the time of enrollment (Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen [as determined by the treating physician and approved by the principal investigator (PI)] may be included)
• A functioning digestive tract with no obstruction
• Subjects must be willing to avoid regular consumption of green tea and curcumin supplements for the duration of trial participation
• Written informed consent obtained from the subject and the ability for the subject to comply with all the study-related procedures
• Subjects of childbearing potential (SOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study. Prior to study enrollment, subjects of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy * SOCBP include any subject who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who is not post-menopausal. Post-menopause is defined as: ** Amenorrhea that has lasted for ≥ 12 consecutive months without another cause, or ** For subjects with irregular menstrual periods who are taking hormone replacement therapy (HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35 mIU/mL
• Subjects with partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study

Exclusion Criteria

• Subjects must not be receiving any other investigational agents
• Subjects of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and following completion of taxane chemotherapy for an additional 6 months for subjects of child bearing potential and 3 months for subjects with partners of childbearing potential
• Subjects who are pregnant or breastfeeding
• Active systemic infection considered to be opportunistic, life threatening or clinically significant at the time of treatment
• Psychiatric illness or social situation that would limit compliance with trial requirements
• Known allergy to turmeric, broccoli, or green tea
• Subjects must not be on treatment with strong CYP3A4 inhibitors such as tacrolimus or on verapamil during the trial
• History of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding (e.g. hemoglobin < 10 mg/dL, Common Terminology Criteria for Adverse Events [CTCAE] version [v] 5.0 grade 3 or higher neutropenia or thrombocytopenia) giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician
• Prisoners or subjects who are involuntarily incarcerated
• Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness
• Subjects demonstrating an inability to comply with the study and/or follow-up procedures
• CTCAE v5.0 grade 2 or higher peripheral sensory or motor neuropathy
• CTCAE v5.0 grade 1 or higher paresthesia
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 × the upper limit of normal (ULN)
• Total bilirubin (TBL) > 1.5 × ULN or > 3 × ULN in the presence of documented Gilbert’s syndrome (unconjugated hyperbilirubinemia)
• Glomerular filtration rate (GFR) < 50 mL/min
• Red blood cell (RBC) infusions < 30 days prior to treatment