CLO22-056: Phase I Trial of Concurrent Nab-paclitaxel and Cisplatin With Radiotherapy for Locally Advanced Cervical Cancer

Concurrent chemoradiotherapy using platinum-containing chemotherapy is the treatment of choice for stages IB3-IVA cervical cancer. A preclinical evaluation of the radiation-modulating effects of nab-paclitaxel in tumor showed that nab-paclitaxel acted as a radiosensitizer and produced supra-additive effects when combined with radiation. However, the use of concurrent nab-paclitaxel and cisplatin with radiation has not been tested for cervical cancer. This study aimed to assess the maximum-tolerated dose (MTD) of nab-paclitaxel (Keaili®) in combination with a fixed dose of cisplatin when given concurrently with radiotherapy to patients for locally advanced cervical cancer (LACC). Method: We conducted a single-center, open-label, single-arm, phase I trial (ClinicalTrials.gov Identifier: NCT04017377). We enrolled patients with stage IB2-IVA cervical cancer. Chemotherapy was administered intravenously on day 1 of radiotherapy weekly. Chemotherapy consisted of at least four cycles of cisplatin 40 mg/m2 and nab-paclitaxel with escalating doses (10, 20, 33, 50, 70 mg/m2). Radiotherapy consisted of intensity modulated radiation therapy in a 50.4 Gy in 28 fractions for five days weekly and intracavitary brachytherapy in a 30 Gy in 5 fractions twice a week. Dose escalation followed a 3 + 3 design. The DLT was defined as grade 3 or 4 nonhematologic toxicity, excluding nausea, vomiting and alopecia, decreased appetite and fatigue, or grade 4 hematologic toxicity. Results: This study was initiated in September, 2019, and enrollment ended in August, 2021. 22 patients were enrolled. Overall, 4 patients (18.0%) experienced DLTs. A DLT was first observed in 1 of 3 patients at 33 mg/m2 (Grade 3 Hypokalemia) but was not observed in the next 3 patients at the same level. 2 patients experienced DLTs (Grade 3 Vascular access complication) at 50mg/m2 and 70mg/m2 dose level respectively. Another DLT (Grade 3 Perineum edema) was observed in 70mg/m2 dose level. The MTD of nab-paclitaxel was found at 50 mg/m2/week. Other major side effects included grade 1-3 leukopenia, diarrhea, and nausea/vomiting. All patients were evaluable for response: 20 patients complete and 1 patient partial responses were obtained with an overall response rate of 95.5%. Conclusion: Weekly administration of 50 mg/m2 nab-paclitaxel when associated to cisplatin 40 mg/m2/week and concurrent radiotherapy can be considered a tolerable and clinically feasible for the treatment of LACC.