Safety, Dose Tolerance, Pharmacokinetics, and Pharmacodynamics Study of CPX-POM in Patients With Advanced Solid Tumors

Phase 1

Completed

• Conditions: Advanced Solid Tumors
• Interventions: Drug: CPX-POM - 600 mg/m^2; Drug: CPX-POM - 30 mg/m^2; Drug: CPX-POM - 360 mg/m^2; Drug: CPX-POM - 1200 mg/m^2; Drug: CPX-POM - 240 mg/m^2; Drug: CPX-POM - 60 mg/m^2; Drug: CPX-POM - 120 mg/m^2; Drug: CPX-POM - 900 mg/m^2

• Registration Number: NCT03348514
• Lead Sponsor: CicloMed LLC

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2017-11-15
• Study First Submitted QC: 2017-11-17
• Study First Posted: 2017-11-21
• Study Start: 2018-01-15
• Primary Completion: 2020-05-31
• Study Completion: 2020-05-31
• Results First Submitted: 2020-10-16
• Results First Submitted QC: 2021-10-19
• Results First Posted: 2021-11-17
• Status Verified: 2021-12
• Last Update Submitted: 2021-12-01
• Last Update Posted: 2021-12-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
CPX-POM - 600 mg/m^2	CPX-POM - 600 mg/m^2	-
CPX-POM - 30 mg/m^2	CPX-POM - 30 mg/m^2	-
CPX-POM - 360 mg/m^2	CPX-POM - 360 mg/m^2	-
CPX-POM - 1200 mg/m^2	CPX-POM - 1200 mg/m^2	-
CPX-POM - 240 mg/m^2	CPX-POM - 240 mg/m^2	-
CPX-POM - 60 mg/m^2	CPX-POM - 60 mg/m^2	-
CPX-POM - 120 mg/m^2	CPX-POM - 120 mg/m^2	-
CPX-POM - 900 mg/m^2	CPX-POM - 900 mg/m^2	-

Primary Outcome Measures

Name	Time	Method
Determine the Maximum Tolerated Dose (MTD) of CPX-POM	Days 1, 2, 3, 4, 5, 6, 10, 22 and 28	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.
Number of Participants With Dose Limiting Toxicities (DLTs) of CPX-POM	Up to 22 days for each cohort	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.

Secondary Outcome Measures

Name	Time	Method
Assess Plasma PK: Terminal Half-life of the Active Metabolite, Ciclopirox (CPX), Following Five Consecutive Days of Once Daily Dosing.	Days 5-6	Determine Terminal Half-Life
Assess Plasma PK: Vd and Vss (mL/kg) of the Active Metabolite, Ciclopirox (CPX), Following Five Consecutive Days of Once Daily Dosing.	Days 5-6	Measure PK parameters Vd (apparent volume of distribution) and Vss (steady state volume of distribution) (mL/kg)
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.	Days 5-6	Measure Percent Dose (%)
Assess Urine PK: Average 24-hour Urine Concentration of the Active Metabolite, Ciclopirox (CPX), Following Five Consecutive Days of Once Daily Dosing.	Days 5-6	Measure urine CPX concentration (uM)
Assess Plasma PK: Cls (mL/hr/kg) of the Active Metabolite, Ciclopirox (CPX), Following Five Consecutive Days of Once Daily Dosing.	Days 5-6	Measure PK parameter Cls (mL/hr/kg) - systemic clearance following single dose (Cls) following single and repeat drug administration.
Assess Plasma PK: Cmax (ng/mL) of the Active Metabolite, Ciclopirox (CPX), Following Five Consecutive Days of Once Daily Dosing.	Days 5-6	Measure PK parameter Cmax (ng/mL)
Assess Plasma PK: AUCss (ng/mL/hr) of the Active Metabolite, Ciclopirox (CPX), Following Five Consecutive Days of Once Daily Dosing.	Days 5-6	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.
Characterize Plasma PK: AUCss/AUCi Accumulation Ratio of the Active Metabolite, Ciclopirox (CPX), Following Five Consecutive Days of Once Daily Dosing.	Days 5-6	Determine PK parameter AUC derived accumulation ratio (AUCss/AUCi ratio)

Trial Locations

Locations (5)

Sarah Cannon Research Institute; 🇺🇸 Denver, Colorado, United States

Florida Cancer Specialists & Research Institute; 🇺🇸 Sarasota, Florida, United States

Stephenson Cancer Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Tennessee Oncology PLLC; 🇺🇸 Nashville, Tennessee, United States

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States