2. Academic Validation
  3. 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

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

  • Invest New Drugs. 2016 Apr;34(2):225-30. doi: 10.1007/s10637-016-0334-y.
Christos E Kyriakopoulos 1,  Elisabeth I Heath 2,  Jens C Eickhoff 3,  Jill Kolesar 3,  Mulusew Yayehyirad 3,  Thomas Moll 4,  George Wilding 3,  Glenn Liu 3
Affiliations

Affiliations

  • 1 University of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison, 600 Highland Avenue, Madison, WI, 53792, USA. [email protected].
  • 2 Karmanos Cancer Institute, Wayne State University, 4100 John R, Detroit, MI, 48201, USA.
  • 3 University of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison, 600 Highland Avenue, Madison, WI, 53792, USA.
  • 4 Adamis Pharmaceuticals Corporation, 11682 El Camino Real, Suite 300, San Diego, CA, 92130, USA.
PMID: 26924129 DOI: 10.1007/s10637-016-0334-y
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.

Keywords

APC-100; Oxidative stress; Phase I; Prostate cancer.

Figures
Products