2018 ASCO Annual Meeting!
Session: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics
Type: Poster Session
Time: Monday June 4, 8:00 AM to 11:30 AM
Location: Hall A
Safety, dose tolerance, pharmacokinetics and pharmacodynamics study of CPX-POM in patients with advanced solid tumors.
Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics
2018 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #433a)
J Clin Oncol 36, 2018 (suppl; abstr TPS2618)
Author(s): Scott James Weir, Robyn Wood, Tammy Ham, Rashida Challenger, Prabhu Ramamoorthy, Greg Reed, Michael Jay Baltezor, Roy A. Jensen, John Arthur Taylor, Shrikant Anant, Michael Dalton, Michael J McKenna, Valentina Zhukova-Harrill, William McCulloch, Howard A. Burris; University of Kansas Cancer Center, Westwood, KS; University of Kansas Medical Center, Kansas City, KS; CicloMed LLC, Kansas City, MO; Cmed Inc., Durham, NC; University of Kansas, Kansas City, KS; Univ of Kansas, Lawrence, KS; The University of Kansas Cancer Center, Kansas City, KS; University of Connecticut Health Center, Farmington, CT; The Gnomon Group, Carrboro, NC; Navigator Life Sciences Advisory, Wilmington, NC; Medical School, Cary, NC; Alba BioPharm Advisors Inc, Raleigh, NC; Sarah Cannon Research Institute, Nashville, TN
Background: Ciclopirox (CPX) is an antifungal agent contained in a number of FDA-approved topical drug products. CPX possesses anticancer activity in a number of in vitro and in vivo preclinical models, however, it’s clinical utility is limited due to low oral bioavailabilty, gastrointestinal toxicity, and poor water solubility. Ciclopirox Prodrug (CPX-POM) selectively delivers its active metabolite, CPX, to the entire urinary tract following systemic administration. In a chemical carcinogen mouse model of bladder cancer, CPX-POM treatment resulted in significant decreases in bladder weight, a clear migration to lower stage tumors, dose-dependent reductions in Ki67 and PCNA staining, and inhibition of Notch 1 and Wnt signaling pathways. Methods: Study CPX-POM-001 (NCT03348514) is an ongoing US multicenter, Phase I, open-label, dose escalation study to evaluate dose-limiting toxicities (DLTs), define the maximum tolerated dose (MTD), and to determine the recommended Phase II dose of IV CPX-POM. Approximately 24 patients with any histologically- or cytologically-confirmed solid tumor type refractory to standard therapy, and also meet other standard Phase I eligibility criteria, will be enrolled in dose escalation cohorts. The MTD will be defined as the dose BELOW that dose which causes DLTs in ≥33% of patients. Safety and tolerability will be based on an assessment of adverse events, physical examinations, vital signs, electrocardiogram, clinical laboratory tests, ophthalmologic assessments, and concomitant medications. Single dose and steady-state pharmacokinetics of CPX-POM, CPX and ciclopirox glucuronide are being characterized in both plasma and urine. Urine ß-glucuronidase activity is also being determined. Single and multiple dose pharmacodynamics of CPX-POM are being characterized by measuring circulating biomarkers of Wnt and Notch cell signaling pathways. Enrollment began in January 2018 at a starting IV CPX-POM dose of 30 mg/m2. Doses are currently being escalated in 100% increments until a ≥Grade 2 is encountered, at which point that cohort and all subsequent cohorts will follow a classical “3 + 3” dose escalation design. Clinical trial information: NCT03348514