A phase II evaluation of elesclomol sodium and weekly paclitaxel in the treatment of recurrent or persistent platinum-resistant ovarian, fallopian tube or primary peritoneal cancer: An NRG oncology/gynecologic oncology group study

Abstract

Objective: Preclinical data suggest elesclomol increases oxidative stress and enhances sensitivity to cytotoxic agents. The objective of this prospective multicenter phase 2 trial was to estimate the activity of IV elesclomol plus weekly paclitaxel in patients with platinum-resistant recurrent ovarian, tubal or peritoneal cancer through the frequency of objective tumor responses (ORR).

Methods: Patients with measurable disease, acceptable organ function, performance status ≤ 2, and one prior platinum containing regimen were eligible. A two-stage design was utilized with a target sample size of 22 and 30 subjects, respectively. Prior Gynecologic Oncology Group studies within the same population involving single agent taxanes showed an ORR of approximately (20%) and served as a historical control for direct comparison. The present study was designed to determine if the regimen had an ORR of ≥40% with 90% power.

Results: Fifty-eight patients were enrolled, of whom 2 received no study treatment and were inevaluable. The median number of cycles was 3 (268 total cycles, range 1-18). The number of patients responding was 11 (19.6%; 90% CI 11.4% to 30.4%) with one complete response. The median progression-free survival and overall survival was 3.6 months and 13.3 months, respectively. The median ORR duration was 9.2 months. Percentages of subjects with grade 3 toxicity included: Neutropenia 9%; anemia 5%; metabolic 5%; nausea 4%; infection 4%; neurologic (mostly neuropathy) 4%; and vascular (mostly thromboembolism) 4%. There were no grade 4 toxicities reported.

Conclusions: This combination was well tolerated but is unworthy of further investigation based on the proportion responding [ClinicalTrials.gov Identifier: NCT00888615].

Keywords: Clinical trial; Elesclomol; Ovarian cancer.

Conflict of interest statement

CONFLICT OF INTEREST

Dr. Angeles Secord received clinical trial grants to her institution from Astra Zeneca, Eisai, Bristol Myers Squibb, Incyte, Amgen, Genentech, Endocyte, Exelixis, Boerhinger Ingelheim, Astex Pharmaceuticals Inc., Prima Biomed, Abbie-Vie, Astellas Pharma Inc., Tesaro, PharmaMar and Merck. She also served on the Advisory Board for Janssen, Clovis, Genentech, Astra Zeneca, Astex, Tesaro, Alexion, Boerhinger Ingelheim, Myriad and Arivave.

Dr. Carol Aghajanian received monies paid to her from Tesaro, Mateon Therapeutics, Clovis, Cerulean, Bayer and VentiRx serving as Honorarium on Advisory Boards and Steering Committee Meetings.

All other co-authors have no conflicts of interest to declare.

Copyright © 2018. Published by Elsevier Inc.

Figures

Figure 1:

Progression-Free Survival and Survival