search
Back to results

A Phase III Study of Nimotuzumab Plus Concurrent Chemoradiotherapy in Loco-regional Esophageal Squamous Cell Carcinoma

Primary Purpose

Prosthesis Survival

Status
Unknown status
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Nimotuzumab
radiotherapy
chemoradiotherapy Paclitaxel
chemoradiotherapy Cisplatin
placebo
Sponsored by
Shandong Cancer Hospital and Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prosthesis Survival

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Signed written informed consent prior to study entry
  2. age：18-70 years
  3. Histopathology confirmed primary esophageal squamous cell carcinoma, meet one of the following criteria (AJCC Staging System，2009，Seventh Edition):Cervical esophageal carcinoma(stage II-III);upper thoracic esophageal cancer or chest esophageal cancer that is unsuitable or refuse surgery (stage II-III)
  4. The existence of measurable lesions (according to Response Evaluation Criteria in Solid Tumors 1.1)
  5. Eastern Cooperative Oncology Group（ECOG）Performance status of 0-1
  6. Possible semi-liquid diet
  7. If there is a risk of pregnancy, male and female subjects must be effective contraception during treatment
  8. Normal bone marrow reserve: neutrophil (ANC) count≥1500/mm3,platelet count≥100,000 /mm3, hemoglobin≥5.6mmol/L(9g/dL)
  9. Normal renal function: serum creatinine≤1.5mg/dl and/or calculated creatinine clearance≥ 60ml/min
  10. Normal hepatic function: bilirubin level≤1.5×ULN, alanine aminotransferase aspartate transaminase（ASAT）& ALST≤1.5×ULN
  11. Subjects tumor tissue available for the relevant biomarker detection

Exclusion Criteria:

  1. Previous chest radiotherapy, systemic chemotherapy, and major esophageal surgery
  2. Concurrent chronic systemic immune therapy, targeted therapy, anti-vascular endothelial growth factor（VEGF）therapy or EGFR-pathway targeting therapy not indicated in this study protocol
  3. Multiple primary carcinomas of the esophagus
  4. Pregnancy (confirmed by urine β-HCG) or lactation period
  5. Uncontrolled diabetes, hypertension, and severe cardiac or pulmonary disease
  6. There are obvious esophageal ulcers, chest and back more than moderate pain, symptoms of esophageal perforation
  7. Unable to comprehend the study requirements or who are not likely to comply with the study requirements
  8. Patients with distant metastasis
  9. Patients with other malignant disease, except for curable non-melanoma skin cancer, cervical carcinoma in situ or malignant disease cure for≥5 years
  10. Known grade 3 or 4 allergic reaction to any of the study treatment
  11. Peripheral neuropathy > grade 1
  12. Participation in another clinical study within the past 30 days
  13. Significant disease which, in the investigator's opinion, would exclude the patient from the study

Sites / Locations

  • Cancer Hospital Chinese Academy of Medical SciencesRecruiting
  • Beijing Cancer HospitalRecruiting
  • Cancer Hospital of Shantou University Medical College
  • The Guangxi Zhuang Autonomous Region Cancer Hospita
  • Affiliated Hospital of Zunyi Medical College
  • Fourth Hospital of Hebei Medical University TumorRecruiting
  • Henan Cancer HospitalRecruiting
  • Jiangsu Cancer HospitalRecruiting
  • Affiliated Hospital of Jiangsu UniversityRecruiting
  • The First Hospital of China Medical UniversityRecruiting
  • Shandong Cancer Hospital and InstituteRecruiting
  • Renji Hospital Shanghai Jiao Tong University School of Medicine
  • The First Hospital of Zhejiang Province
  • Zhejiang Cancer HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Nimotuzumab plus chemoradiotherapy

placebo plus chemoradiotherapy

Arm Description

Nimotuzumab：400mg/w，d1, week 1-7 Paclitaxel：45mg/m2, d1, week 1-7 Cisplatin：20mg/m2, d1, week 1-7 Three dimensional conformal RT（3DCRT）/IntensityModulatedRadiationTherapy（IMRT）：1.8 Gy/f/day, T59.4 Gy/33f,week 1-7

placebo：400mg/w，d1, week 1-7 Paclitaxel：45 mg/m2, d1, week 1-7 Cisplatin：20 mg/m2, d1, week 1-7 Three dimensional conformal RT（3DCRT）/IntensityModulatedRadiationTherapy（IMRT）：1.8 Gy/f/day, T59.4 Gy/33f,week 1-7

Outcomes

Primary Outcome Measures

Over Survival

Secondary Outcome Measures

Full Information

First Posted
December 3, 2014
Last Updated
April 19, 2016
Sponsor
Shandong Cancer Hospital and Institute
search

1. Study Identification

Unique Protocol Identification Number
NCT02409186
Brief Title
A Phase III Study of Nimotuzumab Plus Concurrent Chemoradiotherapy in Loco-regional Esophageal Squamous Cell Carcinoma
Official Title
A Randomized, Controlled, Double-blind Study to Evaluate Efficacy and Survival of Combining Nimotuzumab Plus Concurrent Chemo-radiotherapy in Loco-regional Esophageal Squamous Cell Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
April 2016
Overall Recruitment Status
Unknown status
Study Start Date
March 2015 (undefined)
Primary Completion Date
December 2017 (Anticipated)
Study Completion Date
December 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shandong Cancer Hospital and Institute

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Esophageal cancer is the sixth leading cause of cancer death in worldwide. Over the past 2 decades, well-designed clinical trials have documented the clinical benefits of combination of chemotherapy and radiation for localized esophageal cancer, either as primary therapy or in neoadjuvant setting. Paclitaxel, a radiation sensitizer, has important single-agent activity in esophageal cancer. Paclitaxel-based chemoradiation has been the framework for the recent Radiation Therapy Oncology Group (RTOG) trials of nonoperative management of esophageal cancer. Accumulating clinical evidence suggests that Epidermal Growth Factor Receptor (EGFR) represents a viable target in the treatment of esophageal cancer. EGFR expression is associated with poor prognosis. Nimotuzumab binds specifically to EGFR on both normal and tumor cells and competitively inhibits the binding of Epidermal Growth Factor (EGF) and other ligands, such as Transforming Growth Factor-α (TGF-α). Preclinical models have suggested synergy between nimotuzumab, paclitaxel, cisplatin and radiation. For our phase II study in locally advanced esophageal squamous cell carcinoma (ESCC), the combination of cetuximab and chemoradiotherapy has demonstrated both response and survival benefits. Myara et al reported that nimotuzumab plus concurrent chemoradiation therapy (CCRT) was safe and provided statistically significant objective response (47.8%) and disease control rate (60.9%) in nonresectable ESCC. With all these, the investigators plan to study phase III trial.
Detailed Description
The primary endpoint of this study is overall survival, and the primary hypothesis is the experimental arm will improve median survival time (MST) from 18.2 month to 28.5 month. Assuming bilateral ɑ = 0.05, statistical power of 80%.Each group requires a minimum of 59 cases. Consider the 20% loss factor.The total sample size is 200 cases.It is 100 cases in each group.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Nimotuzumab plus chemoradiotherapy
Arm Type
Active Comparator
Arm Description
Nimotuzumab：400mg/w，d1, week 1-7 Paclitaxel：45mg/m2, d1, week 1-7 Cisplatin：20mg/m2, d1, week 1-7 Three dimensional conformal RT（3DCRT）/IntensityModulatedRadiationTherapy（IMRT）：1.8 Gy/f/day, T59.4 Gy/33f,week 1-7
Arm Title
placebo plus chemoradiotherapy
Arm Type
Placebo Comparator
Arm Description
placebo：400mg/w，d1, week 1-7 Paclitaxel：45 mg/m2, d1, week 1-7 Cisplatin：20 mg/m2, d1, week 1-7 Three dimensional conformal RT（3DCRT）/IntensityModulatedRadiationTherapy（IMRT）：1.8 Gy/f/day, T59.4 Gy/33f,week 1-7
Intervention Type
Drug
Intervention Name(s)
Nimotuzumab
Other Intervention Name(s)
Taixinsheng
Intervention Description
400mg/w，d1, week 1-7
Intervention Type
Radiation
Intervention Name(s)
radiotherapy
Intervention Description
Three dimensional conformal RT（3DCRT）/IntensityModulatedRadiationTherapy（IMRT）：1.8 Gy/f/day, T59.4 Gy/33f,week 1-7
Intervention Type
Drug
Intervention Name(s)
chemoradiotherapy Paclitaxel
Other Intervention Name(s)
Paclitaxel
Intervention Description
45 mg/m2, d1, week 1-7
Intervention Type
Drug
Intervention Name(s)
chemoradiotherapy Cisplatin
Other Intervention Name(s)
Cisplatin
Intervention Description
20 mg/m2, d1, week 1-7
Intervention Type
Other
Intervention Name(s)
placebo
Intervention Description
400mg/w，d1, week 1-7
Primary Outcome Measure Information:
Title
Over Survival
Time Frame
up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed written informed consent prior to study entry age：18-70 years Histopathology confirmed primary esophageal squamous cell carcinoma, meet one of the following criteria (AJCC Staging System，2009，Seventh Edition):Cervical esophageal carcinoma(stage II-III);upper thoracic esophageal cancer or chest esophageal cancer that is unsuitable or refuse surgery (stage II-III) The existence of measurable lesions (according to Response Evaluation Criteria in Solid Tumors 1.1) Eastern Cooperative Oncology Group（ECOG）Performance status of 0-1 Possible semi-liquid diet If there is a risk of pregnancy, male and female subjects must be effective contraception during treatment Normal bone marrow reserve: neutrophil (ANC) count≥1500/mm3,platelet count≥100,000 /mm3, hemoglobin≥5.6mmol/L(9g/dL) Normal renal function: serum creatinine≤1.5mg/dl and/or calculated creatinine clearance≥ 60ml/min Normal hepatic function: bilirubin level≤1.5×ULN, alanine aminotransferase aspartate transaminase（ASAT）& ALST≤1.5×ULN Subjects tumor tissue available for the relevant biomarker detection Exclusion Criteria: Previous chest radiotherapy, systemic chemotherapy, and major esophageal surgery Concurrent chronic systemic immune therapy, targeted therapy, anti-vascular endothelial growth factor（VEGF）therapy or EGFR-pathway targeting therapy not indicated in this study protocol Multiple primary carcinomas of the esophagus Pregnancy (confirmed by urine β-HCG) or lactation period Uncontrolled diabetes, hypertension, and severe cardiac or pulmonary disease There are obvious esophageal ulcers, chest and back more than moderate pain, symptoms of esophageal perforation Unable to comprehend the study requirements or who are not likely to comply with the study requirements Patients with distant metastasis Patients with other malignant disease, except for curable non-melanoma skin cancer, cervical carcinoma in situ or malignant disease cure for≥5 years Known grade 3 or 4 allergic reaction to any of the study treatment Peripheral neuropathy > grade 1 Participation in another clinical study within the past 30 days Significant disease which, in the investigator's opinion, would exclude the patient from the study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jinming Yu, Ph.D, M.D
Phone
13806406293
Email
jn7984729@public.jn.sd.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jinming Yu, Ph.D, M.D
Organizational Affiliation
Shandong Cancer Hospital and Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Xue Meng, Ph.D, M.D
Organizational Affiliation
Shandong Cancer Hospital and Institute
Official's Role
Study Director
Facility Information:
Facility Name
Cancer Hospital Chinese Academy of Medical Sciences
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100021
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lvhua Wang
Phone
13601283715
Email
wlhwq@yahoo.com
First Name & Middle Initial & Last Name & Degree
Zongmei Zhou
Phone
13801389769
Email
zhouzongmei2013@163.com
First Name & Middle Initial & Last Name & Degree
Lvhua Wang
First Name & Middle Initial & Last Name & Degree
Zongmei Zhou
Facility Name
Beijing Cancer Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100142
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guangying Zhu
Phone
13717999977
Email
zgypu@yahoo.com.cn
First Name & Middle Initial & Last Name & Degree
Anhui Shi
Phone
13901136511
Email
anhuidoctor@163.com
First Name & Middle Initial & Last Name & Degree
Guangying Zhu
First Name & Middle Initial & Last Name & Degree
Anhui Shi
Facility Name
Cancer Hospital of Shantou University Medical College
City
Shantou
State/Province
Guangdong
ZIP/Postal Code
515041
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhixiong Lin
Phone
13829638278
Email
zxlin5@qq.com
First Name & Middle Initial & Last Name & Degree
Zhining Yang
Phone
13750443575
Email
36407342@qq.com
First Name & Middle Initial & Last Name & Degree
Zhixiong Lin
First Name & Middle Initial & Last Name & Degree
Zhining Yang
Facility Name
The Guangxi Zhuang Autonomous Region Cancer Hospita
City
Nanning
State/Province
Guangxi
ZIP/Postal Code
530021
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaodong Zhu
Phone
13978873616
Email
zhuxiaodong83@163.com
First Name & Middle Initial & Last Name & Degree
Long Chen
Phone
13977129168
Email
clong6@126.com
First Name & Middle Initial & Last Name & Degree
Xiaodong Zhu
First Name & Middle Initial & Last Name & Degree
Long Chen
Facility Name
Affiliated Hospital of Zunyi Medical College
City
Zunyi
State/Province
Guizhou
ZIP/Postal Code
563099
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hu Ma
Phone
18385034657
Email
mahuab@163.com
First Name & Middle Initial & Last Name & Degree
Xiaoli Gou
Phone
15121201843
Email
526392247@qq.com
First Name & Middle Initial & Last Name & Degree
Hu Ma
First Name & Middle Initial & Last Name & Degree
Xiaoli Gou
Facility Name
Fourth Hospital of Hebei Medical University Tumor
City
Shijiazhuang
State/Province
Hebei
ZIP/Postal Code
50011
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chun Han
Phone
13831105846
Email
hanchun@yahoo.com.cn
First Name & Middle Initial & Last Name & Degree
Jun Wang
Phone
13931182128
Email
wangjunzr@163.com
First Name & Middle Initial & Last Name & Degree
Chun Han
First Name & Middle Initial & Last Name & Degree
Jun Wang
Facility Name
Henan Cancer Hospital
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450008
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jianhua Wang
Phone
13938278827
Email
huajianye@sina.cn
First Name & Middle Initial & Last Name & Degree
Yongshun Chen
Phone
15286831671
Email
yongshun2007@163.com
First Name & Middle Initial & Last Name & Degree
Jianhua Wang
First Name & Middle Initial & Last Name & Degree
Yongshun Chen
Facility Name
Jiangsu Cancer Hospital
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jun Zhu
Phone
15380882705
Email
zhujdr@126.com
First Name & Middle Initial & Last Name & Degree
Hong Ji
Phone
18625155033
Email
dr_jihong@163.com
First Name & Middle Initial & Last Name & Degree
Jun Zhu
First Name & Middle Initial & Last Name & Degree
Hong Ji
Facility Name
Affiliated Hospital of Jiangsu University
City
Zhenjiang
State/Province
Jiangsu
ZIP/Postal Code
212013
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dai Chunhua, PhD
Phone
13952850012
First Name & Middle Initial & Last Name & Degree
Dai Chunhua, PhD
Facility Name
The First Hospital of China Medical University
City
Shenyang
State/Province
Liaoning
ZIP/Postal Code
310022
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guang Li
Phone
13804058616
Email
13804058616@163.com
First Name & Middle Initial & Last Name & Degree
Jun Dang
Phone
13898150850
Email
dangjunsy@163.com
First Name & Middle Initial & Last Name & Degree
Guang Li
First Name & Middle Initial & Last Name & Degree
Jun Dang
Facility Name
Shandong Cancer Hospital and Institute
City
Jinan
State/Province
Shandong
ZIP/Postal Code
250117
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xue Meng, Ph.D, M.D
Phone
86-531-67626142
Email
mengxue5409@126.com
First Name & Middle Initial & Last Name & Degree
Xue Meng, Ph.D, M.D
Facility Name
Renji Hospital Shanghai Jiao Tong University School of Medicine
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200127
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ming Ye
Phone
13901814744
Email
renjiyeming@gmail.com
First Name & Middle Initial & Last Name & Degree
Xin Xu
Phone
13917978366
Email
157198711@qq.com
First Name & Middle Initial & Last Name & Degree
Ming Ye
First Name & Middle Initial & Last Name & Degree
Xin Xu
Facility Name
The First Hospital of Zhejiang Province
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310003
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Senxiang Yan
Phone
13957162839
Email
yansenxiang@zju.edu.cn
First Name & Middle Initial & Last Name & Degree
Haogang Yu
Phone
13516721749
Email
jusn3@163.com
First Name & Middle Initial & Last Name & Degree
Senxiang Yan
First Name & Middle Initial & Last Name & Degree
Haogang Yu
Facility Name
Zhejiang Cancer Hospital
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310022
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ming Chen
Phone
18758875572
Email
chenming@sysucc.org.cn
First Name & Middle Initial & Last Name & Degree
Yujin Xu
Phone
13858037993
Email
xuyj@zjcc.org.cn
First Name & Middle Initial & Last Name & Degree
Ming Chen
First Name & Middle Initial & Last Name & Degree
Yujin Xu

12. IPD Sharing Statement

Learn more about this trial

A Phase III Study of Nimotuzumab Plus Concurrent Chemoradiotherapy in Loco-regional Esophageal Squamous Cell Carcinoma

We'll reach out to this number within 24 hrs