291MO - Determining the maximum tolerated dose of paclitaxel combined with fixed dose of cisplatin for hyperthermic intraperitoneal chemotherapy in ovarian cancer: A multicenter phase I trial

Background

Paclitaxel is an adjunct to cisplatin for hyperthermic intraperitoneal chemotherapy (HIPEC). The purpose of this study was to identify the maximum tolerated dose (MTD) of paclitaxel combined with a fixed dose of cisplatin (75 mg/m2) delivered as HIPEC in patients with ovarian cancer.

Methods

In this multicenter phase I trial, a Bayesian Optimal Interval (BOIN) design was used. The MTD was identified with a target dose-limiting toxicity (DLT) rate of 25%, and the maximum sample size was set at 30 patients. To expedite the trial duration, a cohort size of one was employed for the initial dose escalation, which was then switched to a cohort size of three after observing the first dose-limiting toxicity (DLT). The starting dose of paclitaxel was 175 mg/m². The Data and Safety Monitoring Board made decisions regarding dose escalation or de-escalation in increments of 25 mg/m² for subsequent patient cohorts. This process was repeated until either the prespecified maximum sample size was reached or the number of patients treated at a given dose reached 12.

Results

Between December 2022 and May 2023, 21 patients were treated on the trial. Among the three evaluable patients who received 150 mg/m² paclitaxel, no DLTs were reported. Among the 12 evaluable patients who received 175 mg/m² paclitaxel, two experienced DLTs, including one case of grade 4 neutropenia and one case of grade 4 anemia, neutropenia, and leucopenia. Four out of the six evaluable patients who received 200 mg/m² paclitaxel experienced DLTs, including one case of grade 4 constipation, one case of grade 3 kidney injury, and two cases of grade 4 anemia. The isotonic estimate of the DLT rate in the 175 mg/m² dose group was 0.17 (95% CI, 0.02-0.42), which was the closest to the targeted DLT rate and thus was selected as the MTD.

Conclusions

Paclitaxel, when combined with a fixed dose of cisplatin (75 mg/m²), can be safely administered intraperitoneally at doses of 175 mg/m² in patients with ovarian cancer who received HIPEC (43 °C, 90 minutes) following debulking surgery.

Clinical trial identification

NCT05620654.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Sun Yat-sen Clinical Research Cultivating Program, Grant/Award Number: SYSQ-202207 and SYS-Q-202203. Guangdong Basic and Applied Basic Research Foundation, Grant/Award Number: 2023A1515012647,2021A1515111177 and 2021A1515220142. Guangdong Medical Science and Technology Research Fundation Grant/Award Number: A2022285. Beijing Xisike Clinical Oncology Research Foundation Grant/Award Number: Y-tongshu2021/ms-0133.

Disclosure

All authors have declared no conflicts of interest.