Bradley J Monk1, James T Kauderer2, Katherine M Moxley3, Albert J Bonebrake4, Summer B Dewdney5, Angeles Alvarez Secord6, Frederick R Ueland7, Carolyn M Johnston8, Carol Aghajanian9. 1. Arizona Oncology (US Oncology Network), University of Arizona College of Medicine, Creighton University School of Medicine at St. Joseph Hospital, Phoenix, AZ, USA. Electronic address: Bradley.Monk@usoncology.com. 2. NRG Oncology, Clinical Trial Development Division, Biostatistics & Bioinformatics, Roswell Park, Buffalo, NY, USA. Electronic address: jkauderer@gogstats.org. 3. University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Electronic address: katherine-moxley@ouhsc.edu. 4. Cancer Research for the Ozarks-Cox Health. Ferrell Duncan Clinic GYN-ONC, Springfield, MO 65807, USA. Electronic address: albert.bonebrake@coxhealth.com. 5. Rush University Medical Center, Chicago, IL 60612, USA. Electronic address: summer_dewdney@rush.edu. 6. Duke University Medical Center, Duke Cancer Institute, Durham, NC, USA. Electronic address: angeles.secord@duke.edu. 7. University of Kentucky, Lexington, KY 40536, USA. Electronic address: fuela0@uky.edu. 8. University of Michigan Health System-Cancer Center, Ann Arbor, MI, USA. Electronic address: johnstob@med.umich.edu. 9. Memorial Sloan Kettering Cancer Center and Weill Cornell Medical Center, New York, NY, USA. Electronic address: aghajanc@mskcc.org.
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].
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].