Pharmacokinetics and Safety of Epidiferphane and Taxanes in Breast Cancer Patients
Summary
Patients with breast cancer are commonly treated with taxane chemotherapy. Some very common side effects of taxanes, such as anemia and peripheral neuropathy, are often as not well addressed during treatment, resulting in dose reductions, dose delays and early discontinuation (collectively called relative dose intensity) of these chemotherapy agents in 15-80 % of patients on these drugs. This reduction in relative dose intensity (RDI) results in worse clinical outcomes such as progression free and overall survival. Pre-clinical studies in mouse models subjected to standardized chemotherapy regimens containing paclitaxel or oxaliplatin have shown that the nutritional supplement Epidiferphane reduces both neuropathy and anemia. This study will investigate whether the use of Epidiferphane in patients with breast cancer receiving taxane chemotherapy results in an attenuation of the side effects experienced, as well as an improvement in tumor response rate. The safety and maximum tolerated dose of Epidiferphane in this patient population will also be determined in this study.
Arms & interventions
- DrugEpidiferphane
During the phase I portion of the study, subjects will be assigned to take either two (half target dose) or four (full target dose) Epidiferphane tablets orally three times daily following a 3 + 3 design. Three subjects will be sequentially enrolled at each of the 2 dose levels (beginning with the half target dose) until at least one dose-limiting toxicity (DLT) occurs. Dosing escalation will be stopped if two or more DLTs occur at either dose level. The maximum tolerated dose will be one dose level lower than the dose level at which 2 or more DLTs occur. Dose escalation will occur separately for each taxane regimen (docetaxel or paclitaxel). All subjects in the phase II portion of the study will receive the maximum tolerated dose determined in the phase I portion of the study for their taxane regimen. Subjects in both portions of the study will receive treatment with Epidiferphane for a maximum of three months.
- DrugTaxane Chemotherapy
All subjects on both phases of the study will be concurrently treated with a taxane regimen containing either paclitaxel given weekly, nab-paclitaxel given weekly or every 3 weeks or docetaxel given every 3 weeks. The choice of taxane regimen will be determined by the treating physician prior to consenting to participate in this trial.
Outcome measures
Primary
Cmax of Epidiferphane's components
The Cmax of each of Epidiferphane's components will be based on blood concentration measured prior to taxane chemotherapy administration, as well as at 1, 2 and 24 hours after taxane chemotherapy administration. The Cmax of each of Epidiferphane's components will be the blood concentration measured prior to taxane chemotherapy administration, as well as at 1, 2 and 24 hours after taxane chemotherapy administration.
Time frame: 24 hours
Cmax of taxanes
The Cmax of the taxane chemotherapy agents given will be based on blood concentrations measured prior to taxane chemotherapy administration, as well as at 1, 2 and 24 hours after taxane chemotherapy administration.
Time frame: 24 hours
Concentration at 24 hours (C24 hours) of Epidiferphane's components
The C24 hours of each of Epidiferphane's components will be based on blood concentration measured 24 hours after taxane chemotherapy administration.
Time frame: 24 hours
Concentration at 24 hours (C24 hours) of taxanes
The C24 hours of the taxanes given will be based on blood concentration measured 24 hours after taxane chemotherapy administration.
Time frame: 24 hours
Maximum tolerated dose of Epidiferphane in patients with breast cancer who are being treated with taxanes
Time frame: 4 months
Rate of Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grade 2 or higher neuropathy
Time frame: 4 months
Rate of Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grade 1 or higher anemia
Time frame: 4 months
Secondary
Effect of Epidiferphane on quality of life, as measured by the EORTC QLQ-C30 scale
Time frame: 3 months
Effect of Epidiferphane on quality of life, as measured by the FACT-Taxane scale
Time frame: 3 months
Objective response rate
Time frame: 3 months
Concentration of the neuropathy marker NF-kB, as measured by multiplex cytokine bead analysis or ELISA (enzyme-linked immunosorbent assay)
Time frame: 3 months
Concentration of the neuropathy marker VEGFA, as measured by multiplex cytokine bead analysis or ELISA (enzyme-linked immunosorbent assay)
Time frame: 3 months
Concentration of the neuropathy marker Nrf2, as measured by multiplex cytokine bead analysis or ELISA (enzyme-linked immunosorbent assay)
Time frame: 3 months
Concentration of the neuropathy marker IL18, as measured by multiplex cytokine bead analysis or ELISA (enzyme-linked immunosorbent assay)
Time frame: 3 months
Eligibility criteria
Study locations (1)
University of Florida
Gainesville, Florida, 32608