NCT02812641

Neoadjuvant CCRT With/Without Bevacizumab for Locally Advanced ESCC

A Randomized Trial of Adding Bevacizumab to Neoadjuvant Platinum-Fluorouracil Concurrent Chemoradiation in Locally Advanced Esophageal Squamous Cell Carcinoma

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: National Taiwan University Hospital · Academic / Other
• Sex: All
• Age: 20 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Stage III Esophageal Squamous Cell Carcinoma

Interventions

Type	Name	Description
DRUG	BPF-CCRT (run-in)	Six patients will be enrolled in run-in phase. If \<= 1 patient developed dose-limiting toxicity, the trial will be continued to randomized phase. If \> 1 patients developed dose-limiting toxicities, the protocol will be discontinued.
DRUG	BPF-CCRT (randomized)	Twenty-two patients will be planned to assign to the experimental arm
DRUG	PF-CCRT (randomized)	Twenty-two patients will be planned to assign to the active control arm

Timeline

• Start date: 2016-06-01
• Primary completion: 2019-12-01
• Completion: 2021-12-01
• First posted: 2016-06-24
• Last updated: 2019-03-11

Locations

1 site across 1 country: Taiwan