A Phase 1b Dose-escalation Study of the Safety and Pharmacokinetics of Fixed-dose PCS6422 with Escalating Doses of Capecitabine Administered Orally to Patients with Advanced, Refractory Gastrointestinal Tract Tumors
Categories (click each to see list of all clinical trials associated with that category): GI (ONC)
Current Status: Open
Phase: I
Principal Investigator: Grem, Jean
Contact Information:
Brandie Booker, RN
402-559-8197
brandie.booker@unmc.edu
Eligibility: https://clinicaltrials.gov/study/NCT04861987?term=NCT04861987&rank=1
Summary
Primary Objectives:
To evaluate the safety, dose-limiting toxicities (DLTs), and maximum tolerated dose (MTD) of capecitabine administered to patients with advanced, refractory gastrointestinal tract (GI) tumors using a 7 days on + 7 days off capecitabine regimen ~24 hours after a single, fixed, oral 40 mg dose of PCS6422
To characterize the pharmacokinetic (PK) profiles of capecitabine, 5-fluorouracil (5-FU), and the quantifiable main metabolites α-fluoro-β-alanine (FBAL), 5 -deoxy-5-fluorocytidine (5′-DFCR), and doxifluridine (5′-DFUR) in plasma
Secondary Objective:
To characterize the PK profile of PCS6422 and its major metabolite 5-acetyluracil
To evaluate dihydropyrimidine dehydrogenase (DPD) enzyme activity over time after a single dose of PCS6422 using the ratio of dihydrouracil to uracil as a surrogate to enzyme activity or an analytical method for DPD activity still to be developed
To evaluate the effect of PCS6422 on QT corrected for heart rate (QTc)
To evaluate the incidence of adverse events of special interest (AESI), including the incidence of hand-foot syndrome (HFS)
Exploratory Objective:
To gain preliminary evidence of the antitumor activity of PCS6422 with capecitabine in advanced GI tumors