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

Primary Purpose

Esophageal Neoplasms

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

IMRT simultaneous integrated boost

Nimotuzumab

Paclitaxel

Nedaplatin

Esophagectomy

About this trial

This is an interventional treatment trial for Esophageal Neoplasms focused on measuring Locally advanced esophageal cancer, Radiotherapy and nimotuzumab, Concurrent chemoradiotherapy

Eligibility Criteria

18 Years - 69 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Zefen XiaoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Experimental

Active Comparator

Arm Label

Neoadjuvant nimotuzumab

Neoadjuvant chemotherapy

Radical nimotuzumab

Radical chemotherapy

Arm Description

Radiation：Patients undergo radiotherapy once daily 5 days a week for an average of 4.5 weeks in the absence of disease progression or unacceptable toxicity. IMRT simultaneous integrated boost is used to achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively. Concurrent nimotuzumab: Patients may receive nimotuzumab 400mg per week which start from 1 week before radiotherapy and in the following 4 weeks after enrollment in the absence of disease progression or unacceptable toxicity. Assessment of surgery: Patients eligible for surgery after multiple disciplinary consultation will receive esophagectomy after a 4-6 weeks break after chemoradiation in the absence of any contraindication.

Radiation：Patients undergo radiotherapy once daily 5 days a week for an average of 4.5 weeks in the absence of disease progression or unacceptable toxicity. IMRT simultaneous integrated boost is used to achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively. Concurrent chemotherapy: Patients may receive a dosage range of Paclitaxel from 45 to 60 mg/m2 and Nedaplatin 25mg/m2 per week which start from 1 week before radiotherapy and in the following 4 weeks after enrollment in the absence of disease progression or unacceptable toxicity. Assessment of surgery: Patients eligible for surgery after multiple disciplinary consultation will receive esophagectomy after a 4-6 weeks break after chemoradiation in the absence of any contraindication.

Radiation：Patients undergo radiotherapy once daily 5 days a week for an average of 5.5 weeks in the absence of disease progression or unacceptable toxicity. IMRT simultaneous integrated boost is used to achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively. Concurrent nimotuzumab: Patients may receive nimotuzumab 400mg per week which start from 1 week before radiotherapy and in the following 4 weeks after enrollment in the absence of disease progression or unacceptable toxicity.

Radiation：Patients undergo radiotherapy once daily 5 days a week for an average of 5.5 weeks in the absence of disease progression or unacceptable toxicity. IMRT simultaneous integrated boost is used to achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively. Concurrent chemotherapy: Patients may receive a dosage range of Paclitaxel from 45 to 60 mg/m2 and Nedaplatin 25mg/m2 per week which start from 1 week before radiotherapy and in the following 4 weeks after enrollment in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Pathological response rate

Pathological lymph node metastases rate

R0 resection rate

Adverse events

Secondary Outcome Measures

Disease-free survival (DFS)

Overall survival (OS)

Recurrence rate

Full Information

NCT ID

NCT02858206

First Posted

July 30, 2016

Last Updated

July 25, 2019

Sponsor

Chinese Academy of Medical Sciences

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT02858206

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2019

Overall Recruitment Status

Unknown status

Study Start Date

June 2016 (undefined)

Primary Completion Date

November 2019 (Anticipated)

Study Completion Date

November 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Chinese Academy of Medical Sciences

Collaborators

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Esophageal Neoplasms

Keywords

Locally advanced esophageal cancer, Radiotherapy and nimotuzumab, Concurrent chemoradiotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Neoadjuvant nimotuzumab

Arm Type

Experimental

Arm Description

Arm Title

Neoadjuvant chemotherapy

Arm Type

Active Comparator

Arm Description

Radiation：Patients undergo radiotherapy once daily 5 days a week for an average of 4.5 weeks in the absence of disease progression or unacceptable toxicity. IMRT simultaneous integrated boost is used to achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively. Concurrent chemotherapy: Patients may receive a dosage range of Paclitaxel from 45 to 60 mg/m2 and Nedaplatin 25mg/m2 per week which start from 1 week before radiotherapy and in the following 4 weeks after enrollment in the absence of disease progression or unacceptable toxicity. Assessment of surgery: Patients eligible for surgery after multiple disciplinary consultation will receive esophagectomy after a 4-6 weeks break after chemoradiation in the absence of any contraindication.

Arm Title

Radical nimotuzumab

Arm Type

Experimental

Arm Description

Arm Title

Radical chemotherapy

Arm Type

Active Comparator

Arm Description

Radiation：Patients undergo radiotherapy once daily 5 days a week for an average of 5.5 weeks in the absence of disease progression or unacceptable toxicity. IMRT simultaneous integrated boost is used to achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively. Concurrent chemotherapy: Patients may receive a dosage range of Paclitaxel from 45 to 60 mg/m2 and Nedaplatin 25mg/m2 per week which start from 1 week before radiotherapy and in the following 4 weeks after enrollment in the absence of disease progression or unacceptable toxicity.

Intervention Type

Radiation

Intervention Name(s)

IMRT simultaneous integrated boost

Intervention Description

To achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively

Intervention Type

Drug

Intervention Name(s)

Nimotuzumab

Intervention Description

nimotuzumab 400mg per week which start from 1 week before radiotherapy and in the following 4 weeks

Intervention Type

Drug

Intervention Name(s)

Paclitaxel

Other Intervention Name(s)

Taxol

Intervention Description

Paclitaxel from 45 to 60 mg/m2 per week which start from 1 week before radiotherapy and in the following 4 weeks

Intervention Type

Drug

Intervention Name(s)

Nedaplatin

Intervention Description

Nedaplatin 25mg/m2 per week which start from 1 week before radiotherapy and in the following 4 weeks

Intervention Type

Procedure

Intervention Name(s)

Esophagectomy

Intervention Description

Radical esophagectomy 4-6 weeks after neoadjuvant therapy

Primary Outcome Measure Information:

Title

Pathological response rate

Time Frame

Up to 1 year

Title

Pathological lymph node metastases rate

Time Frame

Up to 1 year

Title

R0 resection rate

Time Frame

Up to 1 year

Title

Adverse events

Time Frame

Up to 2 years

Secondary Outcome Measure Information:

Title

Disease-free survival (DFS)

Time Frame

Up to 2 years

Title

Overall survival (OS)

Time Frame

Up to 2 years

Title

Recurrence rate

Time Frame

Up to 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

69 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Zefen Xiao, MD

Phone

8610-87787643

xiaozefen@sina.com

First Name & Middle Initial & Last Name or Official Title & Degree

Wei Deng, MD

Phone

+8618813019080

sherrydw@126.com

Facility Information:

Facility Name

Zefen Xiao

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100021

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Zefen Xiao, MD

Phone

8610-87787643

xiaozefen@sina.com

First Name & Middle Initial & Last Name & Degree

Wei Deng, MD

Phone

+8618813019080

sherrydw@126.com

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

25691612

Citation

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, Mulcahy MF, Orringer MB, Posey JA, Poultsides GA, Sasson AR, Scott WJ, Strong VE, Varghese TK Jr, Washington MK, Willett CG, Wright CD, Zelman D, McMillian N, Sundar H; National comprehensive cancer network. Esophageal and esophagogastric junction cancers, version 1.2015. J Natl Compr Canc Netw. 2015 Feb;13(2):194-227. doi: 10.6004/jnccn.2015.0028.

Results Reference

result

PubMed Identifier

22646630

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 Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, van der Gaast A; CROSS Group. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012 May 31;366(22):2074-84. doi: 10.1056/NEJMoa1112088.

Results Reference

result

PubMed Identifier

21684205

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. Lancet Oncol. 2011 Jul;12(7):681-92. doi: 10.1016/S1470-2045(11)70142-5. Epub 2011 Jun 16.

Results Reference

result

PubMed Identifier

21462364

Citation

Kranzfelder M, Schuster T, Geinitz H, Friess H, Buchler 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.

Results Reference

result

PubMed Identifier

14967459

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. doi: 10.1016/j.ijrobp.2003.09.097.

Results Reference

result

PubMed Identifier

22555809

Citation

Ramos-Suzarte M, Lorenzo-Luaces P, Lazo NG, Perez ML, Soriano JL, Gonzalez CE, Hernadez IM, Albuerne YA, 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 malignant, non-resectable, epithelial origin esophageal tumours with the humanized anti-epidermal growth factor antibody nimotuzumab combined with radiation therapy and chemotherapy. Cancer Biol Ther. 2012 Jun;13(8):600-5. doi: 10.4161/cbt.19849. Epub 2012 Jun 1.

Results Reference

result

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

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