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

Bradley J. Monk; James T. Kauderer; Katherine M. Moxley; Albert J. Bonebrake; Summer B. Dewdney; Angeles Alvarez Secord; Frederick R. Ueland; Carolyn M. Johnston; Carol Aghajanian

doi:10.1016/j.ygyno.2018.10.001

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

Bradley J. Monk, James T. Kauderer, Katherine M. Moxley, Albert J. Bonebrake, Summer B. Dewdney, Angeles Alvarez Secord, Frederick R. Ueland, Carolyn M. Johnston, Carol Aghajanian

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

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].

Original language	English
Pages (from-to)	422-427
Number of pages	6
Journal	Gynecologic Oncology
Volume	151
Issue number	3
DOIs	https://doi.org/10.1016/j.ygyno.2018.10.001
State	Published - Dec 2018

Bibliographical note

Funding Information:
This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office ( CA 27469 ), the Gynecologic Oncology Group Statistical and Data Center ( CA 37517 ), NRG Oncology ( 1 U10 CA180822 ) and NRG Operations ( U10CA180868 ). The following NRG Oncology/Gynecologic Oncology Group member institutions participated in this study: University of Oklahoma Health Sciences Center, Cancer Research for the Ozarks NCORP, Rush University Medical Center, Duke University Medical Center, University of Kentucky, Michigan Cancer Research Consortium Community Clinical Oncology Program, Stony Brook University Medical Center, Washington University School of Medicine, MD Ander Cancer Center, University of Virginia, The Hospital of Central Connecticut, Iowa-Wide Oncology Research Coalition NCORP, Abington Memorial Hospital, Walter Reed National Military Medical Center, Fred Hutchinson Cancer Research Center, Indiana University Hospital/Melvin and Bren Simon Cancer Center, Wake Forest University Health Sciences, University of California Medical Center at Irvine-Orange Campus, Cooper Hospital University Medical Center, Yale University, University of Wisconsin Hospital and Clinics, Women and Infants Hospital, Saint Joseph's Hospital and Medical Center, Emory University School of Medicine, Piedmont Hospital, Central Illinois CCOP, Virginia Commonwealth University, Mainline Health CCOP, Wichita CCOP, Southeast Cancer Control Consortium CCOP and Northside Hospital.

Funding Information:
This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office (CA 27469), the Gynecologic Oncology Group Statistical and Data Center (CA 37517), NRG Oncology (1 U10 CA180822) and NRG Operations (U10CA180868). The following NRG Oncology/Gynecologic Oncology Group member institutions participated in this study: University of Oklahoma Health Sciences Center, Cancer Research for the Ozarks NCORP, Rush University Medical Center, Duke University Medical Center, University of Kentucky, Michigan Cancer Research Consortium Community Clinical Oncology Program, Stony Brook University Medical Center, Washington University School of Medicine, MD Ander Cancer Center, University of Virginia, The Hospital of Central Connecticut, Iowa-Wide Oncology Research Coalition NCORP, Abington Memorial Hospital, Walter Reed National Military Medical Center, Fred Hutchinson Cancer Research Center, Indiana University Hospital/Melvin and Bren Simon Cancer Center, Wake Forest University Health Sciences, University of California Medical Center at Irvine-Orange Campus, Cooper Hospital University Medical Center, Yale University, University of Wisconsin Hospital and Clinics, Women and Infants Hospital, Saint Joseph's Hospital and Medical Center, Emory University School of Medicine, Piedmont Hospital, Central Illinois CCOP, Virginia Commonwealth University, Mainline Health CCOP, Wichita CCOP, Southeast Cancer Control Consortium CCOP and Northside Hospital.

Publisher Copyright:
© 2018

Keywords

Clinical trial
Elesclomol
Ovarian cancer

ASJC Scopus subject areas

Oncology
Obstetrics and Gynecology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Monk, B. J., Kauderer, J. T., Moxley, K. M., Bonebrake, A. J., Dewdney, S. B., Secord, A. A., Ueland, F. R., Johnston, C. M., & Aghajanian, C. (2018). 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. Gynecologic Oncology, 151(3), 422-427. https://doi.org/10.1016/j.ygyno.2018.10.001

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title = "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",

author = "Monk, {Bradley J.} and Kauderer, {James T.} and Moxley, {Katherine M.} and Bonebrake, {Albert J.} and Dewdney, {Summer B.} and Secord, {Angeles Alvarez} and Ueland, {Frederick R.} and Johnston, {Carolyn M.} and Carol Aghajanian",

note = "Funding Information: This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office ( CA 27469 ), the Gynecologic Oncology Group Statistical and Data Center ( CA 37517 ), NRG Oncology ( 1 U10 CA180822 ) and NRG Operations ( U10CA180868 ). The following NRG Oncology/Gynecologic Oncology Group member institutions participated in this study: University of Oklahoma Health Sciences Center, Cancer Research for the Ozarks NCORP, Rush University Medical Center, Duke University Medical Center, University of Kentucky, Michigan Cancer Research Consortium Community Clinical Oncology Program, Stony Brook University Medical Center, Washington University School of Medicine, MD Ander Cancer Center, University of Virginia, The Hospital of Central Connecticut, Iowa-Wide Oncology Research Coalition NCORP, Abington Memorial Hospital, Walter Reed National Military Medical Center, Fred Hutchinson Cancer Research Center, Indiana University Hospital/Melvin and Bren Simon Cancer Center, Wake Forest University Health Sciences, University of California Medical Center at Irvine-Orange Campus, Cooper Hospital University Medical Center, Yale University, University of Wisconsin Hospital and Clinics, Women and Infants Hospital, Saint Joseph's Hospital and Medical Center, Emory University School of Medicine, Piedmont Hospital, Central Illinois CCOP, Virginia Commonwealth University, Mainline Health CCOP, Wichita CCOP, Southeast Cancer Control Consortium CCOP and Northside Hospital. Funding Information: This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office (CA 27469), the Gynecologic Oncology Group Statistical and Data Center (CA 37517), NRG Oncology (1 U10 CA180822) and NRG Operations (U10CA180868). The following NRG Oncology/Gynecologic Oncology Group member institutions participated in this study: University of Oklahoma Health Sciences Center, Cancer Research for the Ozarks NCORP, Rush University Medical Center, Duke University Medical Center, University of Kentucky, Michigan Cancer Research Consortium Community Clinical Oncology Program, Stony Brook University Medical Center, Washington University School of Medicine, MD Ander Cancer Center, University of Virginia, The Hospital of Central Connecticut, Iowa-Wide Oncology Research Coalition NCORP, Abington Memorial Hospital, Walter Reed National Military Medical Center, Fred Hutchinson Cancer Research Center, Indiana University Hospital/Melvin and Bren Simon Cancer Center, Wake Forest University Health Sciences, University of California Medical Center at Irvine-Orange Campus, Cooper Hospital University Medical Center, Yale University, University of Wisconsin Hospital and Clinics, Women and Infants Hospital, Saint Joseph's Hospital and Medical Center, Emory University School of Medicine, Piedmont Hospital, Central Illinois CCOP, Virginia Commonwealth University, Mainline Health CCOP, Wichita CCOP, Southeast Cancer Control Consortium CCOP and Northside Hospital. Publisher Copyright: {\textcopyright} 2018",

year = "2018",

month = dec,

doi = "10.1016/j.ygyno.2018.10.001",

language = "English",

volume = "151",

pages = "422--427",

number = "3",

}

Monk, BJ, Kauderer, JT, Moxley, KM, Bonebrake, AJ, Dewdney, SB, Secord, AA, Ueland, FR, Johnston, CM & Aghajanian, C 2018, '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', Gynecologic Oncology, vol. 151, no. 3, pp. 422-427. https://doi.org/10.1016/j.ygyno.2018.10.001

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. / Monk, Bradley J.; Kauderer, James T.; Moxley, Katherine M. et al.

In: Gynecologic Oncology, Vol. 151, No. 3, 12.2018, p. 422-427.

Research output: Contribution to journal › Article › peer-review

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 - Funding Information: This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office ( CA 27469 ), the Gynecologic Oncology Group Statistical and Data Center ( CA 37517 ), NRG Oncology ( 1 U10 CA180822 ) and NRG Operations ( U10CA180868 ). The following NRG Oncology/Gynecologic Oncology Group member institutions participated in this study: University of Oklahoma Health Sciences Center, Cancer Research for the Ozarks NCORP, Rush University Medical Center, Duke University Medical Center, University of Kentucky, Michigan Cancer Research Consortium Community Clinical Oncology Program, Stony Brook University Medical Center, Washington University School of Medicine, MD Ander Cancer Center, University of Virginia, The Hospital of Central Connecticut, Iowa-Wide Oncology Research Coalition NCORP, Abington Memorial Hospital, Walter Reed National Military Medical Center, Fred Hutchinson Cancer Research Center, Indiana University Hospital/Melvin and Bren Simon Cancer Center, Wake Forest University Health Sciences, University of California Medical Center at Irvine-Orange Campus, Cooper Hospital University Medical Center, Yale University, University of Wisconsin Hospital and Clinics, Women and Infants Hospital, Saint Joseph's Hospital and Medical Center, Emory University School of Medicine, Piedmont Hospital, Central Illinois CCOP, Virginia Commonwealth University, Mainline Health CCOP, Wichita CCOP, Southeast Cancer Control Consortium CCOP and Northside Hospital. Funding Information: This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office (CA 27469), the Gynecologic Oncology Group Statistical and Data Center (CA 37517), NRG Oncology (1 U10 CA180822) and NRG Operations (U10CA180868). The following NRG Oncology/Gynecologic Oncology Group member institutions participated in this study: University of Oklahoma Health Sciences Center, Cancer Research for the Ozarks NCORP, Rush University Medical Center, Duke University Medical Center, University of Kentucky, Michigan Cancer Research Consortium Community Clinical Oncology Program, Stony Brook University Medical Center, Washington University School of Medicine, MD Ander Cancer Center, University of Virginia, The Hospital of Central Connecticut, Iowa-Wide Oncology Research Coalition NCORP, Abington Memorial Hospital, Walter Reed National Military Medical Center, Fred Hutchinson Cancer Research Center, Indiana University Hospital/Melvin and Bren Simon Cancer Center, Wake Forest University Health Sciences, University of California Medical Center at Irvine-Orange Campus, Cooper Hospital University Medical Center, Yale University, University of Wisconsin Hospital and Clinics, Women and Infants Hospital, Saint Joseph's Hospital and Medical Center, Emory University School of Medicine, Piedmont Hospital, Central Illinois CCOP, Virginia Commonwealth University, Mainline Health CCOP, Wichita CCOP, Southeast Cancer Control Consortium CCOP and Northside Hospital. 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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Monk BJ, Kauderer JT, Moxley KM, Bonebrake AJ, Dewdney SB, Secord AA et al. 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. Gynecologic Oncology. 2018 Dec;151(3):422-427. doi: 10.1016/j.ygyno.2018.10.001

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

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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Fingerprint

Cite this