Abstract：
BACKGROUND: The prognosis of patients with advanced biliary tract cancer (BTC) is still poor, and new strategies improving patients\' outcome are needed. In our trial we investigated safety and activity of nab-paclitaxel in combination with gemcitabine and oxaliplatin as first-line systemic treatment for patients with advanced BTC.
METHODS: In this investigator-initiated, multicenter, dose-escalation, single-arm phase I/II trial, patients were accrued into cohorts of 3 patients and dose escalation was performed following the standard 3 + 3 rule. Primary endpoint was the proportion of patients free from progression at 6 months. Secondary endpoints included safety and tolerability of the combination; progression-free survival (PFS); overall survival (OS); objective response rate (ORR); duration of response.
RESULTS: Between July 2017 and December 2020, 67 patients were treated. Among the 10 patients in the phase I, no dose-limiting toxicity was observed, and dose level 2 was defined as recommended phase II dose for the phase II part. At data cutoff, the 6-month PFS rate was 49.1 % (95 % CI 40.8-57.5 %) with 28 patients out of 57 free from progression or death at 6 months. Median PFS was 6.3 months (95 % CI 3.6-10.1) and median OS was 12.4 months (95 % CI 8-23). ORR was 20.89 %. Most common grade 3 and grade 1-2 drug-related adverse events were neutropenia and peripheral neuropathy, respectively.
CONCLUSIONS: Triple chemotherapy demonstrated a favorable safety profile. However, the study did not meet its primary endpoint. Future studies will clarify the benefit of chemotherapy combinations in different settings. This trial is registered with ClinicalTrials.gov, NCT03943043.
METHODS: In this investigator-initiated, multicenter, dose-escalation, single-arm phase I/II trial, patients were accrued into cohorts of 3 patients and dose escalation was performed following the standard 3 + 3 rule. Primary endpoint was the proportion of patients free from progression at 6 months. Secondary endpoints included safety and tolerability of the combination; progression-free survival (PFS); overall survival (OS); objective response rate (ORR); duration of response.
RESULTS: Between July 2017 and December 2020, 67 patients were treated. Among the 10 patients in the phase I, no dose-limiting toxicity was observed, and dose level 2 was defined as recommended phase II dose for the phase II part. At data cutoff, the 6-month PFS rate was 49.1 % (95 % CI 40.8-57.5 %) with 28 patients out of 57 free from progression or death at 6 months. Median PFS was 6.3 months (95 % CI 3.6-10.1) and median OS was 12.4 months (95 % CI 8-23). ORR was 20.89 %. Most common grade 3 and grade 1-2 drug-related adverse events were neutropenia and peripheral neuropathy, respectively.
CONCLUSIONS: Triple chemotherapy demonstrated a favorable safety profile. However, the study did not meet its primary endpoint. Future studies will clarify the benefit of chemotherapy combinations in different settings. This trial is registered with ClinicalTrials.gov, NCT03943043.
摘要：
背景：晚期胆道癌（BTC）患者的预后仍然很差，和改善患者预后的新策略是必要的。在我们的试验中，我们调查了nab-紫杉醇联合吉西他滨和奥沙利铂作为晚期BTC患者一线全身治疗的安全性和活性。
方法：在这个研究者发起的，多中心，剂量递增，单臂I/II期试验，将患者纳入3例患者的队列,并按照标准3+3规则进行剂量递增.主要终点是6个月时无进展患者的比例。次要终点包括组合的安全性和耐受性；无进展生存期（PFS）；总生存期（OS）；客观缓解率（ORR）；缓解持续时间。
结果：在2017年7月至2020年12月期间，67例患者接受了治疗。在第一阶段的10名患者中，未观察到剂量限制性毒性，剂量水平2定义为II期部分的推荐II期剂量.在数据截止时，6个月PFS率为49.1%(95%CI40.8~57.5%),57例患者中有28例患者在6个月时无进展或死亡.中位PFS为6.3个月（95%CI3.6-10.1），中位OS为12.4个月（95%CI8-23）。ORR为20.89%。最常见的3级和1-2级药物相关的不良事件是中性粒细胞减少和周围神经病变。分别。
结论：三联化疗显示良好的安全性。然而,研究未达到主要终点.未来的研究将阐明化疗组合在不同环境中的益处。该试验已在ClinicalTrials.gov注册，NCT03943043。
方法：在这个研究者发起的，多中心，剂量递增，单臂I/II期试验，将患者纳入3例患者的队列,并按照标准3+3规则进行剂量递增.主要终点是6个月时无进展患者的比例。次要终点包括组合的安全性和耐受性；无进展生存期（PFS）；总生存期（OS）；客观缓解率（ORR）；缓解持续时间。
结果：在2017年7月至2020年12月期间，67例患者接受了治疗。在第一阶段的10名患者中，未观察到剂量限制性毒性，剂量水平2定义为II期部分的推荐II期剂量.在数据截止时，6个月PFS率为49.1%(95%CI40.8~57.5%),57例患者中有28例患者在6个月时无进展或死亡.中位PFS为6.3个月（95%CI3.6-10.1），中位OS为12.4个月（95%CI8-23）。ORR为20.89%。最常见的3级和1-2级药物相关的不良事件是中性粒细胞减少和周围神经病变。分别。
结论：三联化疗显示良好的安全性。然而,研究未达到主要终点.未来的研究将阐明化疗组合在不同环境中的益处。该试验已在ClinicalTrials.gov注册，NCT03943043。
