Simultaneous Integrated Boost Radiotherapy and Concurrent Nimotuzumab or Chemotherapy for Esophageal Carcinoma

Esophageal Neoplasms Clinical Trial

Official title:

Prospective, Non-randomised Phase Ⅱ Study of Simultaneous Integrated Boost Radiotherapy and Concurrent Nimotuzumab or Chemotherapy for Locally Advanced Esophageal Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02858206
• Other study ID #: 16-082/1161
• Status: Recruiting
• Phase: Phase 2
• Start date: June 2016
• Est. completion date: November 2021

Study information

• Verified date: July 2019
• Source: Chinese Academy of Medical Sciences
• Contact: Zefen Xiao, MD
• Phone: 8610-87787643
• Email: xiaozefen[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This prospective, non-randomized phase II study aims to compare radiotherapy and concurrent nimotuzumab with concurrent chemoradiotherapy to obtain a non-inferior pCR rate and pathological lymph node metastases rate in premise of lower toxicities in locally advanced esophageal cancer.

Description:

In the era of IMRT and concurrent chemoradiotherapy, the 5-year overall survival of esophageal cancer increase from 10% to about 20%-40%, recurrence rate decrease from 80% to 50%-60%, and local recurrence remains to be the most important type of failure. What called for is to enhance local control without increasing toxicity to improve survival. The investigators have found effective and safe regimen of simultaneously integrated boost radiotherapy in previous study, which can achieve high dose in tumor area with avoid of normal tissues. However, a recent prospective study reported that neoadjuvant chemoradiotherapy resulted in much higher toxicities compares to neoadjuvant chemotherapy (46% vs. 15%, p= 0.04). Although chemoradiotherapy reached a higher pCR rate (28% vs. 9%, p=0.002), patients did not differ in survival in two groups.

Nimotuzumab is an humanized monoclonal antibody against EGFR. Radiotherapy combines Nimotuzumab reveals synergistic effect in head and neck cancers with lower toxicities as compared to concurrent chemoradiotherapy. Our previous study showed that EGFR expression rate were similar in esophageal cancer and head and neck cancers. Based on above results, the investigators design this study which aims to obtain a non-inferior pCR rate and pathological lymph node metastases rate in premise of lower toxicities.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: November 2021
• Est. primary completion date: November 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 69 Years

Eligibility

Inclusion Criteria:

• Diagnosis of clinical stage T1-4aN0-1M1a untreated squamous esophageal carcinoma

• KPS=70

• Adequate organ function

• No known history of drug allergy

Exclusion Criteria:

• Known drug allergy

• Insufficient hepatorenal function

• Severe cardiovascular diseases, diabetes with uncontrolled blood sugar, mental disorders, uncontrolled severe infection, active ulceration which need intervention.

Related Conditions & MeSH terms

• Esophageal Neoplasms

Intervention

Radiation:
• IMRT simultaneous integrated boost
To achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively

Drug:
• Nimotuzumab
nimotuzumab 400mg per week which start from 1 week before radiotherapy and in the following 4 weeks
• Paclitaxel
Paclitaxel from 45 to 60 mg/m2 per week which start from 1 week before radiotherapy and in the following 4 weeks
• Nedaplatin
Nedaplatin 25mg/m2 per week which start from 1 week before radiotherapy and in the following 4 weeks

Procedure:
• Esophagectomy
Radical esophagectomy 4-6 weeks after neoadjuvant therapy

Locations

Country	Name	City	State
China	Zefen Xiao	Beijing	Beijing

Sponsors (11)

Lead Sponsor	Collaborator
Chinese Academy of Medical Sciences	Affiliated Hospital of Hebei University, Beijing Army General Hospital, Beijing Hospital, Fujian Cancer Hospital, Hebei Medical University Fourth Hospital, Henan Cancer Hospital, Peking University First Hospital, The Affiliated Hospital of Inner Mongolia Medical University, The First Affiliated Hospital with Nanjing Medical University, Tianjin Medical University Cancer Institute and Hospital

Country where clinical trial is conducted

China, 

References & Publications (6)

Ajani JA, D'Amico TA, Almhanna K, Bentrem DJ, Besh S, Chao J, Das P, Denlinger C, Fanta P, Fuchs CS, Gerdes H, Glasgow RE, Hayman JA, Hochwald S, Hofstetter WL, Ilson DH, Jaroszewski D, Jasperson K, Keswani RN, Kleinberg LR, Korn WM, Leong S, Lockhart AC, — View Citation

Harari PM, Huang SM. Combining EGFR inhibitors with radiation or chemotherapy: will preclinical studies predict clinical results? Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):976-83. Review. — View Citation

Kranzfelder M, Schuster T, Geinitz H, Friess H, Büchler P. Meta-analysis of neoadjuvant treatment modalities and definitive non-surgical therapy for oesophageal squamous cell cancer. Br J Surg. 2011 Jun;98(6):768-83. doi: 10.1002/bjs.7455. Epub 2011 Apr 4 — View Citation

Ramos-Suzarte M, Lorenzo-Luaces P, Lazo NG, Perez ML, Soriano JL, Gonzalez CE, Hernadez IM, Albuerne YÁ, Moreno BP, Alvarez ES, Callejo IP, Alert J, Martell JA, Gonzalez YS, Gonzalez YS, Astudillo de la Vega H, Ruiz-Garcia EB, Ramos TC. Treatment of malig — View Citation

Sjoquist KM, Burmeister BH, Smithers BM, Zalcberg JR, Simes RJ, Barbour A, Gebski V; Australasian Gastro-Intestinal Trials Group. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. — View Citation

van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, ten Kate FJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Spillenaar — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathological response rate		Up to 1 year
Primary	Pathological lymph node metastases rate		Up to 1 year
Primary	R0 resection rate		Up to 1 year
Primary	Adverse events		Up to 2 years
Secondary	Disease-free survival (DFS)		Up to 2 years
Secondary	Overall survival (OS)		Up to 2 years
Secondary	Recurrence rate		Up to 2 years