Journal article
A multicenter phase 1/2a dose-escalation study of the antioxidant moiety of vitamin E 2,2,5,7,8-pentamethyl-6-chromanol (APC-100) in men with advanced prostate cancer
Investigational new drugs, Vol.34(2), pp.225-230
04/01/2016
DOI: 10.1007/s10637-016-0334-y
PMCID: PMC6844069
PMID: 26924129
Abstract
Background A phase 1/2a dose escalation study of APC-100 (2,2,5,7,8-Pentamethyl-6-chromanol) was conducted to determine maximum tolerated dose (MTD), recommended phase 2 dose, toxicities and efficacy in men with castrate-resistant prostate cancer (CRPC). Methods This open label phase 1/2a study utilizes a time-to-event reassessment method (TITE-CRM) design. Patients in cohorts of 3 were treated with escalating doses of APC-100 (900 mg-2400 mg) orally once daily continuously. Cycles were 28 days. Results Twenty patients with CRPC were enrolled in the dose escalation cohort. One possible DLT (elevated ALT) was seen at dose level 1. No other DLTs were seen and no dose reductions were required. Most frequent AEs included nausea (grade 1 in 6 patients) and elevated transaminases (grade 1-3 in 5 patients). After enrolment of 20 patients the MTD was not reached, however the maximal feasible dose was exceeded due to the number of capsules ingested. Five of the 20 patients had stable disease as their best response. The median progression free survival (PFS) for the cohort was 2.8 months (range 1-8). Conclusions APC-100 is a novel agent with dual mechanism of action functioning both as potent antioxidant as well as antiandrogen. No detectable APC-100 was found in the plasma at dose level 5 (2100 mg) and it was felt that maximal feasibility was nearly reached. APC-100 is being reformulated as a tablet to allow further dose escalation. Once a recommended phase 2 dose is established, future studies in prostate cancer chemoprevention should be conducted.
Details
- Title: Subtitle
- A multicenter phase 1/2a dose-escalation study of the antioxidant moiety of vitamin E 2,2,5,7,8-pentamethyl-6-chromanol (APC-100) in men with advanced prostate cancer
- Creators
- Christos E. Kyriakopoulos - University of Wisconsin Carbone Cancer CenterElisabeth I. Heath - The Barbara Ann Karmanos Cancer InstituteJens C. Eickhoff - University of Wisconsin–MadisonJill Kolesar - University of Wisconsin Carbone Cancer CenterMulusew Yayehyirad - University of Wisconsin Carbone Cancer CenterThomas Moll - Adamis PharmaceuticalsGeorge Wilding - University of Wisconsin Carbone Cancer CenterGlenn Liu - University of Wisconsin Carbone Cancer Center
- Resource Type
- Journal article
- Publication Details
- Investigational new drugs, Vol.34(2), pp.225-230
- Publisher
- Springer Nature
- DOI
- 10.1007/s10637-016-0334-y
- PMID
- 26924129
- PMCID
- PMC6844069
- ISSN
- 0167-6997
- eISSN
- 1573-0646
- Number of pages
- 6
- Grant note
- Adamis Pharmaceuticals Corporation, San Diego, CA P30 CA014520 / National Institute of Health/National Cancer Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) PC131993 / Prostate Cancer Clinical Trials Consortium
- Language
- English
- Date published
- 04/01/2016
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984695787902771
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