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

April 19, 2016 updated by: Jinming Yu, Shandong Cancer Hospital and Institute

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

200

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100142
        • Recruiting
        • Beijing Cancer Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Guangying Zhu
        • Sub-Investigator:
          • Anhui Shi
      • Beijing, Beijing, China, 100021
        • Recruiting
        • Cancer Hospital Chinese Academy of Medical Sciences
        • Contact:
        • Sub-Investigator:
          • Zongmei Zhou
    • Guangdong
      • Shantou, Guangdong, China, 515041
        • Not yet recruiting
        • Cancer Hospital of Shantou University Medical College
        • Contact:
        • Contact:
        • Principal Investigator:
          • Zhixiong Lin
        • Sub-Investigator:
          • Zhining Yang
    • Guangxi
      • Nanning, Guangxi, China, 530021
        • Not yet recruiting
        • The Guangxi Zhuang Autonomous Region Cancer Hospita
        • Contact:
        • Contact:
        • Principal Investigator:
          • Xiaodong Zhu
        • Sub-Investigator:
          • Long Chen
    • Guizhou
      • Zunyi, Guizhou, China, 563099
        • Not yet recruiting
        • Affiliated Hospital of Zunyi Medical College
        • Contact:
        • Contact:
        • Principal Investigator:
          • Hu Ma
        • Sub-Investigator:
          • Xiaoli Gou
    • Hebei
      • Shijiazhuang, Hebei, China, 50011
        • Recruiting
        • Fourth Hospital of Hebei Medical University Tumor
        • Contact:
        • Contact:
        • Principal Investigator:
          • Chun Han
        • Sub-Investigator:
          • Jun Wang
    • Henan
      • Zhengzhou, Henan, China, 450008
        • Recruiting
        • Henan Cancer Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jianhua Wang
        • Sub-Investigator:
          • Yongshun Chen
    • Jiangsu
      • Nanjing, Jiangsu, China, 210000
        • Recruiting
        • Jiangsu Cancer Hospital
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Hong Ji
      • Zhenjiang, Jiangsu, China, 212013
        • Recruiting
        • Affiliated Hospital of Jiangsu University
        • Contact:
          • Dai Chunhua, PhD
          • Phone Number: 13952850012
        • Principal Investigator:
          • Dai Chunhua, PhD
    • Liaoning
      • Shenyang, Liaoning, China, 310022
        • Recruiting
        • The First Hospital of China Medical University
    • Shandong
      • Jinan, Shandong, China, 250117
        • Recruiting
        • Shandong Cancer Hospital and Institute
        • Contact:
        • Sub-Investigator:
          • Xue Meng, Ph.D, M.D
    • Shanghai
      • Shanghai, Shanghai, China, 200127
        • Not yet recruiting
        • Renji Hospital Shanghai Jiao Tong University School of Medicine
        • Contact:
        • Contact:
        • Principal Investigator:
          • Ming Ye
        • Sub-Investigator:
          • Xin Xu
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310022
        • Recruiting
        • Zhejiang Cancer Hospital
        • Principal Investigator:
          • Ming Chen
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Yujin Xu
      • Hangzhou, Zhejiang, China, 310003
        • Not yet recruiting
        • The First Hospital of Zhejiang Province
        • Contact:
        • Contact:
        • Principal Investigator:
          • Senxiang Yan
        • Sub-Investigator:
          • Haogang Yu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Nimotuzumab plus chemoradiotherapy
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
Drug: Nimotuzumab
400mg/w，d1, week 1-7
Other Names:
  • Taixinsheng
Radiation: radiotherapy
Three dimensional conformal RT（3DCRT）/IntensityModulatedRadiationTherapy（IMRT）：1.8 Gy/f/day, T59.4 Gy/33f,week 1-7
Drug: chemoradiotherapy Paclitaxel
45 mg/m2, d1, week 1-7
Other Names:
  • Paclitaxel
Drug: chemoradiotherapy Cisplatin
20 mg/m2, d1, week 1-7
Other Names:
  • Cisplatin
Placebo Comparator: placebo plus chemoradiotherapy
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
Radiation: radiotherapy
Three dimensional conformal RT（3DCRT）/IntensityModulatedRadiationTherapy（IMRT）：1.8 Gy/f/day, T59.4 Gy/33f,week 1-7
Drug: chemoradiotherapy Paclitaxel
45 mg/m2, d1, week 1-7
Other Names:
  • Paclitaxel
Drug: chemoradiotherapy Cisplatin
20 mg/m2, d1, week 1-7
Other Names:
  • Cisplatin
Other: placebo
400mg/w，d1, week 1-7

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Over Survival
Time Frame: up to 5 years
up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shandong Cancer Hospital and Institute

Investigators

  • Study Director: Xue Meng, Ph.D, M.D, Shandong Cancer Hospital and Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2015

Primary Completion (Anticipated)

December 1, 2017

Study Completion (Anticipated)

December 1, 2021

Study Registration Dates

First Submitted

December 3, 2014

First Submitted That Met QC Criteria

April 3, 2015

First Posted (Estimate)

April 6, 2015

Study Record Updates

Last Update Posted (Estimate)

April 21, 2016

Last Update Submitted That Met QC Criteria

April 19, 2016

Last Verified

April 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NXCEL1311

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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