Clinical trial NCT03611985: Phase I/IIa Study of Pharmacokinetics and Safety of Epidiferphane™ and Taxanes in Breast Cancer Patients
Official title: Study of Pharmacokinetics and Safety of Epidiferphane™ and Taxanes in Breast Cancer Patients
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Keywords: breast cancer
Epidiferphane
taxane
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: Prana Therapeutics
First posted: 2018-08-02
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* Must be at least 18 years of age
* Subjects on the phase I portion must have a clinical diagnosis of metastatic breast cancer. Subjects on the phase IIa portion must have a clinical diagnosis of breast cancer of any stage and histology.
* Must be about to start a new chemotherapy treatment regimen containing either paclitaxel given weekly or docetaxel given every 3 weeks at UF Health
* Must continue cancer therapy at UF Health for at least the next three months
* A functioning digestive tract with no obstruction
* Subjects must be willing to avoid regular consumption of green tea for the duration of trial participation.
* Written informed consent obtained from the subject or the subject's legal representative and the ability for the subject to comply with all the study-related procedures.
* Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study.
* Males with female partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study.

Exclusion Criteria:

* Must not be receiving any other investigational agents
* Females or males 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 women of child bearing potential and 3 months for men with partners of child bearing potential.
* Females 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 verapamil or tacrolimus 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)
* Glomerular filtration rate (GFR) \<50 mL/min

Primary outcomes:
measure: Cmax of Epidiferphane's components
timeFrame: 24 hours
measure: Rate of occurrence of DLTs by dose level in patients with breast cancer who are being treated with taxanes
timeFrame: 4 months
measure: Maximum tolerated dose of Epidiferphane in patients with breast cancer who are being treated with taxanes
timeFrame: 3 months
measure: Cmax of taxanes
timeFrame: 3 weeks
measure: Number of adverse events (graded according to CTCAE v5.0 criteria) by epidiferphane dose level
timeFrame: 4 months
measure: Concentration at 24 hours (C24 hours) of Epidiferphane's components
timeFrame: 24 hours
measure: Concentration at 24 hours (C24 hours) of taxanes
timeFrame: 24 hours
Secondary outcomes:
measure: Change in CTCAE grade 2 or higher neuropathy and anemia, as compared to historically reported rates for the occurrence of each of these events
timeFrame: 4 months
measure: Effect of Epidiferphane on tumor response rate, as measured by RECIST 1.1 criteria and pathologic tumor response at surgery
timeFrame: 3 months
measure: Effect of Epidiferphane on the neuropathy marker NF-kB, as measured by multiplex cytokine bead analysis
timeFrame: 3 weeks
measure: Effect of Epidiferphane on the neuropathy marker VEGFA, as measured by multiplex cytokine bead analysis
timeFrame: 3 weeks
measure: Effect of Epidiferphane on the neuropathy marker Nrf2, as measured by multiplex cytokine bead analysis
timeFrame: 3 weeks
measure: Effect of Epidiferphane on the neuropathy marker IL18, as measured by multiplex cytokine bead analysis
timeFrame: 3 weeks
measure: Effect of Epidiferphane on quality of life, as measured by the EORTC QLQ-C30 scale
timeFrame: 3 months
measure: Effect of Epidiferphane on quality of life, as measured by the FACT-Taxane scale
timeFrame: 3 months
Other outcomes:
Locations:
Study officials:
affiliation: University of Florida
name: Coy Heldermon, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: