Research Appraisals

Cancer chemotherapy and pharmacology

A randomized, open-label, two-way crossover clinical trial to evaluate the food effect on pharmacokinetics and safety of DHP107 in patients with advanced solid tumors: the FEEL study

PURPOSE: The phase 1, randomized, open-label, two-way crossover FEEL study assessed the effect of food on the pharmacokinetics of DHP107, an oral paclitaxel with a novel lipid formulation designed to be systemically absorbed without Cremophor EL, in patients with advanced solid tumors. METHODS: Patients were randomized 1:1 to DHP107 (200 mg/m2 orally twice daily on Days 1, 8, 15 every 28 days for two cycles) treatment sequences: fasted-fed (first DHP107 dose administered after overnight fast; n = 13) and fed-fasted (first DHP107 dose administered after a high-fat meal; n = 12). The primary objective was to evaluate the effect of food on DHP107 pharmacokinetics. The secondary objective was DHP107 safety; efficacy was also assessed (both in all patients regardless of dosing sequence). RESULTS: Mean systemic exposures were similar for paclitaxel and its metabolites under fed and fasted conditions. Geometric mean ratios (fed:fasted) for paclitaxel were: maximum concentration (Cmax), 101.00% (95% CI 91.93-110.95%); area under the curve (AUC0-72), 102.92% (95% CI 95.04-111.45%); and AUC0-inf 104.76% (95% CI 96.44-113.80%), meeting criteria for no food effect. Common adverse events across the study period included diarrhea (fasted-fed 61.5%; fed-fasted 41.7%), vomiting (fasted-fed 30.8%; fed-fasted 8.3%), and neutropenia (fasted-fed 23.1%; fed-fasted 16.7%). Two fed-fasted patients (16.7%) had partial responses and six had stable disease (50.0%); seven fasted-fed patients had stable disease (53.8%). CONCLUSION: This study suggests that the pharmacokinetics of DHP107 are unaffected by food and DHP107 can be taken with or without food. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04675528; 107CS-7.