Pharmacokinetics and Safety of Epidiferphane and Taxanes in Breast Cancer Patients

NCT05074290 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: UF-BRE-007
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Breast Cancer

Keywords

breast cancer; taxanes; Epidiferphane

Outcome Measures

Primary Outcomes (7)

• 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.

  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.

  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.

  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.

  24 hours

• Maximum tolerated dose of Epidiferphane in patients with breast cancer who are being treated with taxanes

  4 months

• Rate of Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grade 2 or higher neuropathy

  4 months

• Rate of Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grade 1 or higher anemia

  4 months

Secondary Outcomes (7)

• Effect of Epidiferphane on quality of life, as measured by the EORTC QLQ-C30 scale

  3 months

• Effect of Epidiferphane on quality of life, as measured by the FACT-Taxane scale

  3 months

• Objective response rate

  3 months

• Concentration of the neuropathy marker NF-kB, as measured by multiplex cytokine bead analysis or ELISA (enzyme-linked immunosorbent assay)

  3 months

• Concentration of the neuropathy marker VEGFA, as measured by multiplex cytokine bead analysis or ELISA (enzyme-linked immunosorbent assay)

  3 months

Study Arms (1)

Epidiferphane + taxane chemotherapy

EXPERIMENTAL

Drug: Epidiferphane; Drug: Taxane Chemotherapy

Interventions

Epidiferphane DRUG

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.

Epidiferphane + taxane chemotherapy

Taxane Chemotherapy DRUG

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.

Epidiferphane + taxane chemotherapy

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be at least 18 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.
• 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 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 weekly at 260 mg/m2
• Docetaxel every three weeks at 75-100 mg/m2
• An ECOG Performance Status less than or equal to 3 based on treating physician assessment
• Must continue cancer therapy at UF Health for at least the next three months
• 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 \[as determined by the treating physician and approved by the PI\] 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.
• Subjects with partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study.

You may not qualify if:

• 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 therapy for an additional 6 months for subjects of child bearing potential and 3 months for subjects with partners of child bearing 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, CTCAE 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 v 5.0 grade 2 or higher peripheral sensory or motor neuropathy
• CTCAE v 5.0 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)

Sponsors & Collaborators

• University of Florida: lead

Study Sites (1)

University of Florida

Gainesville, Florida, 32608, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Coy Heldermon

  University of Florida

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Priya Gurjar

CONTACT

352-273-6772; PMO@cancer.ufl.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2021
• First Posted: October 12, 2021
• Study Start: March 30, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 17, 2026

Record last verified: 2026-02

Locations

US (1)