Article Text
Abstract
Objectives To evaluate the maximum tolerated dose/maximum administered dose, safety, pharmacokinetic, and efficacy profiles of ombrabulin combined with paclitaxel and carboplatin in Japanese patients with solid tumors.
Methods Ombrabulin (25, 30, or 35 mg/m2) combined with paclitaxel (175 or 200 mg/m2) and carboplatin (AUC5 or AUC6) was administered by intravenous infusion once every 3 weeks to patients with advanced solid tumors, including cervical, ovarian, and uterine cancers. The maximum tolerated dose/maximum administered dose was defined based on the dose-limiting toxicity at cycle 1. Efficacy was assessed based on Response Evaluation Criteria In Solid Tumors (RECIST).
Results In total, 18 patients were recruited for this dose escalation study. One out of six patients treated with the highest doses of combination of ombrabulin (35 mg/m2), paclitaxel (200 mg/m2), and carboplatin (AUC6) presented a dose-limiting toxicity consisting of grade 3 Escherichia urinary tract infection. This dose was defined as the maximum tolerated dose of ombrabulin. The most frequent treatment-emergent adverse events were alopecia (83.3%), neutropenia and fatigue (72.2% each), decreased appetite, nausea, diarrhea, arthralgia, and myalgia (66.7% each). The grade 3–4 treatment-emergent adverse events included neutropenia (61.1%), Escherichia urinary tract infection, drug hypersensitivity, syncope, pulmonary embolism, and hydronephrosis (one patient each). In efficacy evaluation, seven patients achieved partial response or better (38.9%), including one complete response, and seven of 18 patients had stable disease (38.9%). Pharmacokinetic profiles in this Japanese study were comparable with those observed in the previous study without Japanese patients.
Conclusions Although the maximum tolerated dose/maximum administered dose of ombrabulin (35 mg/m2) with taxane-platinum combination may be tolerable in Japanese patients in the first cycle, the dosages in the repeated treatment should be carefully selected for further study.
Trial registration number NCT01293630.
- uterine cervical neoplasms
- ovarian neoplasms
- uterine neoplasms
- adenocarcinoma
Data availability statement
Data are not available for phase 1 study according to Sanofi’s data-sharing rule. Data are available upon reasonable request. Qualified researchers may request access to patient level data and related study documents, including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of our trial participants. Further details on Sanofi’s data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.vivli.org/.
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Data availability statement
Data are not available for phase 1 study according to Sanofi’s data-sharing rule. Data are available upon reasonable request. Qualified researchers may request access to patient level data and related study documents, including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of our trial participants. Further details on Sanofi’s data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.vivli.org/.
Footnotes
Contributors All authors have contributed to the study conceptualization, validation of the data, writing original draft of the manuscript. YS contributed to the curation and formal analysis of the data. KM and KF were responsible for investigation and resources. EE-F was responsible for the management and coordination of the study. KM, YS, and KF were guarantor. All authors have reviewed, revised, and approved the manuscript for publication.
Funding This study was funded by Sanofi.
Competing interests KM reports grants from Sanofi, during the conduct of the study; grants from ICON Japan; grants and personal fees from MSD, Chugai, Novartis, ONO, Astra Zeneca, and Eisai; personal fees from Taiho, Eli Lilly, Kyowa Kirin, Pfizer, and AbbVie, outside the submitted work. YS reports personal fees and other from Sanofi, outside the submitted work. EE-F reports personal fees from Sanofi, during the conduct of the study. KF reports grants from Sanofi, during the conduct of the study; grants and personal fees from Astra Zeneca, Chugai-Roche, Eisai, MSD, Taiho, Zeria, Nano Carrier, and Takeda; grants from Immunogen, Oncotherapy, Regeneron, Genmab; personal fees from Daiichi Sankyo, Kyowa Kirin, and Mochida, outside the submitted work.
Provenance and peer review Not commissioned; externally peer reviewed.
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