Florence Atrafi1, Herlinde Dumez2, Ron H J Mathijssen3, Catharine W Menke van der Houven van Oordt4, Cristianne J F Rijcken5, Rob Hanssen5, Ferry A L M Eskens3, Patrick Schöffski2. 1. Department of Medical Oncology, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands. Electronic address: f.atrafi@erasmusmc.nl. 2. Department of General Medical Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium. 3. Department of Medical Oncology, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands. 4. Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, location Vrije Universiteit Medisch Centrum, Amsterdam, the Netherlands. 5. Cristal Therapeutics, Maastricht, the Netherlands.
Abstract
BACKGROUND: CPC634 is docetaxel entrapped in core-cross linked polymeric micelles. In preclinical studies, CPC634 demonstrated enhanced pharmacokinetics and improved therapeutic index. This phase I dose escalation study is the first-in-human study with CPC634. METHODS: adult patients with advanced solid tumours received CPC634 intravenously either 3-weekly (Q3W) (part 1, dose range 15-100 mg/m2), 2-weekly (Q2W) (part 2, 45 mg/m2) or Q3W with dexamethasone premedication (part 3, 60 mg/m2). RESULTS: thirty-three patients were enrolled. Skin toxicity was dose limiting (DLT) at ≥60 mg/m2 in part 1 and at 45 mg/m2 in part 2 and was the most common CPC634 related grade ≥ 3 adverse event (24%). With dexamethasone premedication no DLTs were observed at 60 mg/m2 Q3W. CPC634 exhibited a dose-proportional pharmacokinetic profile. At 60 mg/m2, the plasma area under the curve was 4067.5 ± 2974.0 ng/h/mL and the peak plasma level 217.3 ± 91.9 ng/mL with a half-life of 39.7 ± 9.4 h for released docetaxel. CONCLUSION: CPC634 could be administered safely upon pretreatment with dexamethasone. Cumulative skin toxicity was the main DLT. The recommended phase 2 dose was determined at 60 mg/m2 Q3W with dexamethasone premedication.
BACKGROUND:CPC634 is docetaxel entrapped in core-cross linked polymeric micelles. In preclinical studies, CPC634 demonstrated enhanced pharmacokinetics and improved therapeutic index. This phase I dose escalation study is the first-in-human study with CPC634. METHODS: adult patients with advanced solid tumours received CPC634 intravenously either 3-weekly (Q3W) (part 1, dose range 15-100 mg/m2), 2-weekly (Q2W) (part 2, 45 mg/m2) or Q3W with dexamethasone premedication (part 3, 60 mg/m2). RESULTS: thirty-three patients were enrolled. Skin toxicity was dose limiting (DLT) at ≥60 mg/m2 in part 1 and at 45 mg/m2 in part 2 and was the most common CPC634 related grade ≥ 3 adverse event (24%). With dexamethasone premedication no DLTs were observed at 60 mg/m2 Q3W. CPC634 exhibited a dose-proportional pharmacokinetic profile. At 60 mg/m2, the plasma area under the curve was 4067.5 ± 2974.0 ng/h/mL and the peak plasma level 217.3 ± 91.9 ng/mL with a half-life of 39.7 ± 9.4 h for released docetaxel. CONCLUSION:CPC634 could be administered safely upon pretreatment with dexamethasone. Cumulative skin toxicity was the main DLT. The recommended phase 2 dose was determined at 60 mg/m2 Q3W with dexamethasone premedication.
Authors: Lauren Repp; Christopher J Unterberger; Zhengqing Ye; John B Feltenberger; Steven M Swanson; Paul C Marker; Glen S Kwon Journal: Nanomaterials (Basel) Date: 2021-10-17 Impact factor: 5.076
Authors: Nicole Strittmatter; Jennifer I Moss; Alan M Race; Daniel Sutton; Jaime Rodriguez Canales; Stephanie Ling; Edmond Wong; Joanne Wilson; Aaron Smith; Colin Howes; Josephine Bunch; Simon T Barry; Richard J A Goodwin; Marianne B Ashford Journal: Theranostics Date: 2022-02-14 Impact factor: 11.556