This is a first-in-human, Phase I, multicenter, open label, dose escalation study to evaluate the DLTs and MTD and to determine the recommended Phase 2 dose (RP2D) of CPX-POM administered IV in patients with any histologically- or cytologically-confirmed solid tumor type.
The study will initially employ an accelerated escalation design, with a single patient enrolled in each cohort (i.e., Single-Patient Cohorts). The initial patient will receive CPX-POM at a starting dose of 30 mg/m2. Doses will be escalated (doubling), until a ≥Grade 2 toxicity (with the exception of alopecia), is encountered. Subsequently that and all subsequent cohorts will follow a classical "3+3" dose escalation design. Note: Fosciclopirox is the generic name for CPX-POM.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
19
CPX-POM
CPX-POM
CPX-POM
Sarah Cannon Research Institute
Denver, Colorado, United States
Florida Cancer Specialists & Research Institute
Sarasota, Florida, United States
University of Kansas Medical Center
Kansas City, Kansas, United States
Stephenson Cancer Center
Oklahoma City, Oklahoma, United States
Number of Participants With Dose Limiting Toxicities (DLTs) of CPX-POM
The primary objective of this study is to evaluate the dose limiting toxicities (DLTs) of ciclopirox phosphoryloxymethyl ester (CPX-POM) administered intravenously (IV) and establish the CPX POM dose recommended for further investigation. A DLT will include some Grade 3 or 4 AEs (as assessed by CTCAE version 4.03) if deemed related to study drug. In addition, any patient who is unable to receive 80% of the expected dose of CPX-POM (i.e., patients who are unable to receive at least 4 of the 5 scheduled doses) because of AEs will be considered to have a DLT. In order to identify any DLTs, safety assessments including AEs, physical examinations, vital signs, and clinical laboratory tests will be conducted during each study visit through Day 22.
Time frame: Up to 22 days for each cohort
Determine the Maximum Tolerated Dose (MTD) of CPX-POM
The primary objective of this study is to evaluate the maximum tolerated dose (MTD) of ciclopirox phosphoryloxymethyl ester (CPX-POM) administered intravenously (IV) and establish the CPX POM dose recommended for further investigation. MTD was determined by testing increasing doses up to 1200 mg/m\^2 by IV. The MTD is defined as the dose BELOW that dose which causes DLTs in ≥33% of patients.
Time frame: Days 1, 2, 3, 4, 5, 6, 10, 22 and 28
Assess Plasma PK: Cmax (ng/mL) of the Active Metabolite, Ciclopirox (CPX), Following Five Consecutive Days of Once Daily Dosing.
Measure PK parameter Cmax (ng/mL)
Time frame: Days 5-6
Assess Plasma PK: Terminal Half-life of the Active Metabolite, Ciclopirox (CPX), Following Five Consecutive Days of Once Daily Dosing.
Determine Terminal Half-Life
Time frame: Days 5-6
Assess Plasma PK: AUCss (ng/mL/hr) of the Active Metabolite, Ciclopirox (CPX), Following Five Consecutive Days of Once Daily Dosing.
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CPX-POM
CPX-POM
CPX-POM
CPX-POM
CPX-POM
Tennessee Oncology PLLC
Nashville, Tennessee, United States
Measure PK parameter area-under-the-plasma-drug/metabolite-concentration-time curve (ng/mL/hr) following single dose (AUC) and at steady-state AUCss following single and repeat drug administration.
Time frame: Days 5-6
Assess Plasma PK: Cls (mL/hr/kg) of the Active Metabolite, Ciclopirox (CPX), Following Five Consecutive Days of Once Daily Dosing.
Measure PK parameter Cls (mL/hr/kg) - systemic clearance following single dose (Cls) following single and repeat drug administration.
Time frame: Days 5-6
Assess Plasma PK: Vd and Vss (mL/kg) of the Active Metabolite, Ciclopirox (CPX), Following Five Consecutive Days of Once Daily Dosing.
Measure PK parameters Vd (apparent volume of distribution) and Vss (steady state volume of distribution) (mL/kg)
Time frame: Days 5-6
Characterize Plasma PK: AUCss/AUCi Accumulation Ratio of the Active Metabolite, Ciclopirox (CPX), Following Five Consecutive Days of Once Daily Dosing.
Determine PK parameter AUC derived accumulation ratio (AUCss/AUCi ratio)
Time frame: Days 5-6
Assess Urine PK: Percent (%) of the CPX-POM Dose Excreted in Urine as CPX-POM and Metabolites, Following Five Consecutive Days of Once Daily Dosing.
Measure Percent Dose (%)
Time frame: Days 5-6
Assess Urine PK: Average 24-hour Urine Concentration of the Active Metabolite, Ciclopirox (CPX), Following Five Consecutive Days of Once Daily Dosing.
Measure urine CPX concentration (uM)
Time frame: Days 5-6