TY - JOUR
T1 - 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
T2 - An NRG oncology/gynecologic oncology group study
AU - Monk, Bradley J.
AU - Kauderer, James T.
AU - Moxley, Katherine M.
AU - Bonebrake, Albert J.
AU - Dewdney, Summer B.
AU - Secord, Angeles Alvarez
AU - Ueland, Frederick R.
AU - Johnston, Carolyn M.
AU - Aghajanian, Carol
N1 - Publisher Copyright:
© 2018
PY - 2018/12
Y1 - 2018/12
N2 - 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].
AB - 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].
KW - Clinical trial
KW - Elesclomol
KW - Ovarian cancer
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U2 - 10.1016/j.ygyno.2018.10.001
DO - 10.1016/j.ygyno.2018.10.001
M3 - Article
C2 - 30309721
AN - SCOPUS:85054443944
SN - 0090-8258
VL - 151
SP - 422
EP - 427
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 3
ER -