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.

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].

An assessment of age and other factors influencing protocol versus alternative treatments for patients with epithelial ovarian cancer referred to member institutions: a Gynecologic Oncology Group study.

OBJECTIVE: To assess the frequency with which patients with epithelial ovarian cancer are enrolled in prospective Gynecologic Oncology Group (GOG) treatment studies and to assess whether enrollment is influenced by patient age or other factors. METHODS: The study was open to patients with primary, previously untreated epithelial ovarian cancer referred to member institutions. Eligible patients provided written informed consent to have demographic and medical records data submitted to the protocol database for analysis. Pathologic diagnosis was confirmed by central review. Demographic and clinical data, including coexisting medical conditions, tumor stage, grade, and histology, surgical procedures, planned postoperative therapy, and reason/s (if applicable) a patient was not treated per GOG protocol, were collected. RESULTS: Nine hundred and forty-eight patients were initially eligible. Subsequently, 137 (15%) patients were excluded based on pathology (low malignant potential tumors), as were 10 whose invasive disease was unstaged. Among 801 eligible patients, 36% were > or =65 years of age, 52% had papillary serous tumors, and 73% had stage III/IV disease. In patients aged <65 years, 67% were stage III/IV compared to 82% of patients > or =65 years of age. The mean age was 5.5 years greater for patients with stage III/IV versus stage I/II disease. Compared to their younger counterparts, older patients with stage III/IV disease were less likely to enter into a GOG treatment protocol. Most common reasons were patient ineligibility (33%), refusal (29%), and investigator decision (20%). CONCLUSION: Age appears to be an important factor influencing treatment selection among patients with stage III/IV ovarian cancer. In addition to reviewing eligibility criteria, practitioners' attitudes should be monitored to assure that elderly patients are not inappropriately denied participation in GOG clinical trials.