A Randomized Trial of Adding Bevacizumab to Neoadjuvant Platinum-Fluorouracil Concurrent Chemoradiation in Locally Advanced Esophageal Squamous Cell Carcinoma
试验速览
- 阶段
- 2 期
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Dose-limiting toxicity (run-in phase)
研究概览
简要总结
Esophageal squamous cell carcinoma (ESCC) is one of the ten leading cancers in Taiwanese male. The prognosis is poor with a five-year overall survival rate of 10 to 30 %. Randomized clinical trials have demonstrated that trimodality therapy (TMT), consisted of neoadjuvant concurrent chemoradiation (CCRT) and radical esophagectomy, improves the overall survival for patients with locally advanced disease. Despite of the advancement, the outcome remained unsatisfactory with the median progression-free survival around 20 to 25 months and median overall survival around 30 months. It is know that the most important prognostic factor is whether a pathological complete response can be achieved after neoadjuvant CCRT. However, the use of new generation chemotherapeutic agent taxanes and epidermal growth factor inhibitors (such as Cetuximab) failed to significantly improve prognosis comparing to the standard platinum-fluorouracil (PF) regimen. As a consequence, it is mandatory to develop new chemotherapeutic regimen for CCRT.
In previous prospective studies, investigators used proximal ligation assay technology to identify serum VEGF-A in correlation with the pathological response and prognosis for patients receiving neoadjuvant CCRT plus radical esophagectomy for locally advanced ESCC. Other investigators also showed high VEGF expression correlating to poor outcome. Therefore, investigators generate the hypothesis that adding vascular endothelial growth factor (VEGF) monoclonal antibody, Bevacizumab, to standard neoadjuvant CCRT may improve outcome for patients with ESCC. Meanwhile, several prospective clinical studies have shown the feasibility, safety, and activity of adding Bevacizumab to chemotherapy, CCRT, or combined modality therapy including surgery, either in head and neck cancer, esophageal cancer, or esophagogastric junction adenocarcinoma. However, its efficacy should be further investigated in larger prospective trials and little is known about the activity and toxicity of Bevacizumab in ESCC due to small number of reported cases. In the present clinical trial, investigators plan to investigate whether incorporation of Bevacizumab into standard neoadjuvant PF-CCRT will improve treatment response and increase pathological complete response rate. Investigators will also evaluate associated biomarkers in relation to prognosis. By the present research, investigators expect to develop a new TMT regimen for this poor prognostic disease.
详细描述
This study is a randomized trial to compare the outcomes between patients receiving neoadjuvant PF-CCRT plus Bevacizumab (BPF-CCRT) or PF-CCRT alone. Investigators design to enrol 6 patients in the run-in phase, and 44 patients in the randomized phase (22 patients in each group) to develop the preliminary evidence for using Bevacizumab in ESCC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
BPF-CCRT (Run-in Phase)
Neoadjuvant CCRT with Bevacizumab, Cisplatin and 5-fluorouracil
Chemotherapy:
Bevacizumab(B): 10 mg/kg on day 1
Cisplatin(P): 75 mg/m2 on day 1
5-fluorouracil(F): 24 hours continuous infusion of 1,000 mg/m2 on days 1-4
Radiotherapy: 40 Gy/20 fractions: days 1-5, weeks 1-4
干预措施: BPF-CCRT (run-in) (Drug)
BPF-CCRT (Randomized Phase)
Neoadjuvant CCRT with Bevacizumab, Cisplatin and 5-fluorouracil
Chemotherapy:
Bevacizumab(B): 10 mg/kg on day 1
Cisplatin(P): 75 mg/m2 on day 1
5-fluorouracil(F): 24 hours continuous infusion of 1,000 mg/m2 on days 1-4
Radiotherapy: 40 Gy/20 fractions: days 1-5, weeks 1-4
干预措施: BPF-CCRT (randomized) (Drug)
PF-CCRT (Randomized Phase)
Neoadjuvant CCRT with Cisplatin and 5-fluorouracil
Chemotherapy:
Cisplatin(P): 75 mg/m2 on day 1
5-fluorouracil(F): 24 hours continuous infusion of 1,000 mg/m2 on days 1-4
Radiotherapy: 40 Gy/20 fractions: days 1-5, weeks 1-4
干预措施: PF-CCRT (randomized) (Drug)
结局指标
主要结局
Dose-limiting toxicity (run-in phase)
时间窗: 30 days after radical esophagectomy
Number of participant in the run-in phase with life-threatening adverse event or death, which is probable or definitely associated with bevacizumab
Pathological complete response rate (randomized phase)
时间窗: 8 weeks
Number of participant achieved pathological complete response, which is defined as complete surgical resection of all gross tumours without residual microscopic invasive carcinoma at primary tumor location and dissected lymph nodes.
次要结局
- Acute toxicity(From date of CCRT until 90 days after CCRT starts)
- Patient reported outcome (Quality of Life questionnaire of cancer patients)(At baseline, 2, 4 weeks after CCRT, before surgery, 1 month after surgery, and every 3 month thereafter until unequivocal progression, hospice care, or death, assessed up to 24 months)
- Late toxicity(From 90 days after CCRT starts until the date of death from any cause, up to 60 months)
- Patient reported outcome (Quality of Life questionnaire of esophageal cancer patients)(At baseline, 2, 4 weeks after CCRT, before surgery, 1 month after surgery, and every 3 month thereafter until unequivocal progression, hospice care, or death, assessed up to 24 months)
- Image response(at baseline and before surgery (8 weeks))
- Metabolic Image response(at baseline and before surgery (8 weeks))
- Progression-free survival(From date of enrolment until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 60 months)
- Overall survival(From date of enrollment until the date of death from any cause, assessed up to 60 months)