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Changes in Tumor Tissue and Serum Biomarkers Before and After Cetuximab Combined With Preoperative Radiotherapy in Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma

Primary Purpose

Locally Advanced Thoracic Middle-lower Segment Esophageal Squamous Cell Carcinoma

Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
preoperative radiotherapy
cetuximab
Sponsored by
Sichuan Cancer Hospital and Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Locally Advanced Thoracic Middle-lower Segment Esophageal Squamous Cell Carcinoma focused on measuring tumor tissue and serum biomarkers, cetuximab, preoperative radiotherapy, esophageal squamous cell carcinoma

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

(1)18 to 65 years old,male or female (2)Pathologically or cytologically proven thoracic middle-lower esophageal squamous cell carcinoma; (3)clinical stage II or stage III; (4)Primary tumors can be measured; (5)Karnofsky score >70; (6)Estimated life expectancy of at least 12 weeks; (7)reproductive age women should ensure that before entering the study period contraception; (8)Hemoglobin≥90.0g/dL,white blood cell count(WBC)≥ 4000 cells/mm³,Platelet count≥100,000 cells/mm³; (9)Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 times upper limit of normal,bilirubin normal; (10)Creatinine normal OR creatinine clearance ≥ 60 mL/min; (11)Patients have good compliance to treatment and follow-up of acceptance; (12)Forced expiratory volume in one second(FEV1) ≥ 1.5 litre or ≥ 75% of the reference value; (13)Considered operable (i.e. appropriate organ functions and ability to undergo general anesthesia); (14)No severe or uncontrolled cardiovascular disease; (15)No active uncontrolled infection;

Exclusion Criteria:

  1. Patient who have distant metastasis
  2. The primary tumor or lymph node already received surgical treatment (except for biopsy);
  3. Patient who received radiotherapy for primary tumor or lymph node;
  4. Patient who received the the epidermal growth factor targeted therapy;
  5. Patient who received chemotherapy or immunotherapy;
  6. Patient who suffered from other malignant tumor;
  7. Epidermal growth factor receptor(EGFR)mutation(-);
  8. Patient who have taken other drug test within 1 month;
  9. Pregnant woman or Lactating Women and Women in productive age who refuse to take contraception in observation period;
  10. Subject with a severe allergic history or idiosyncratic;
  11. Subject with severe pulmonary and cardiopathic disease history; Refuse or incapable to sign the informed consent form of participating this trial;
  12. Drug abuse or alcohol addicted;
  13. Subject with a Personality or psychiatric diseases, people with no legal; capacity or people with limited capacity for civil conduct;

Sites / Locations

  • Sichuan Cancer Hospital & InstituteRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm A

Arm Description

All patients in the arm receive cetuximab combined with preoperative radiotherapy at first. 4-6 weeks after the rdiaotherapy,patients receive right thoracotomy with three incisions radical surgery.

Outcomes

Primary Outcome Measures

Expression of Survivin protein in Esophageal Squamous Cell Carcinoma before and after Radiotherapy
Survivin, an inhibitor of apoptosis protein, is highly expressed in most cancers and associated with radiotherapy resistance, increased tumor recurrence, and shorter patient survival.
Expression of p53 in Esophageal Squamous Cell Carcinoma before and after Radiotherapy
p53 (also known as protein 53 or tumor protein 53), is a tumor suppressor protein that in humans is encoded by the TP53 gene.p53 is important in multicellular organisms and involved in preventing cancer.
changes of serum vascular endothelial growth factor(VEGF)level before and after radiotherapy
Vascular endothelial growth factor (VEGF) is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis.

Secondary Outcome Measures

Quality of life (QOL)
Quality of life (QOL) as measured by European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30)
Overall survival
time from randomization to death
PFS(progression-free survival)
time from randomization to one of the following events, whichever comes first: Tumor progression at any time (progression of primary tumor or local lymph nodes, appearance of new lesions) Recurrence at local, regional or distant site after surgery Death from any cause
local control rate(LCR)
Time to locoregional failure after R0 resection
Pathological remission
grade 3-5 adverse events
Grade 3-5 adverse events as assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0,such as esophagitis、pneumonitis and hematologic toxicity

Full Information

First Posted
April 13, 2014
Last Updated
March 16, 2020
Sponsor
Sichuan Cancer Hospital and Research Institute
Collaborators
Daping Hospital and the Research Institute of Surgery of the Third Military Medical University, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Southwest Hospital, China, Xinqiao Hospital of Chongqing
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1. Study Identification

Unique Protocol Identification Number
NCT02123381
Brief Title
Changes in Tumor Tissue and Serum Biomarkers Before and After Cetuximab Combined With Preoperative Radiotherapy in Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma
Official Title
Changes in Tumor Tissue and Serum Biomarkers Before and After Cetuximab Combined With Preoperative Radiotherapy in Locally Advanced Middle or Lower Thoracic Esophageal Squamous Cell Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Unknown status
Study Start Date
April 2014 (undefined)
Primary Completion Date
July 2020 (Anticipated)
Study Completion Date
July 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sichuan Cancer Hospital and Research Institute
Collaborators
Daping Hospital and the Research Institute of Surgery of the Third Military Medical University, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Southwest Hospital, China, Xinqiao Hospital of Chongqing

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study aim to investigate Changes in tumor tissue and serum biomarkers before and after cetuximab combined with preoperative radiotherapy in locally advanced thoracic middle-lower segment esophageal squamous cell carcinoma.We want to find one or more effective biomarkers to predict and evaluate the patients who will be benefit from cetuximab combined with preoperative radiotherapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced Thoracic Middle-lower Segment Esophageal Squamous Cell Carcinoma
Keywords
tumor tissue and serum biomarkers, cetuximab, preoperative radiotherapy, esophageal squamous cell carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Experimental
Arm Description
All patients in the arm receive cetuximab combined with preoperative radiotherapy at first. 4-6 weeks after the rdiaotherapy,patients receive right thoracotomy with three incisions radical surgery.
Intervention Type
Radiation
Intervention Name(s)
preoperative radiotherapy
Intervention Description
Patients receive intensity modulated radiation therapy(IMRT) or image-guided radiation therapy(IGRT)from week 1 to week 4,once a day, 5 times per week. Radiotherapy dose:95% gross tumor volume(GTV-T) 40Gy/20f,GTV-N 40Gy/20f,CTV-T 40Gy/20f,CTV-N 40Gy/20f.
Intervention Type
Drug
Intervention Name(s)
cetuximab
Other Intervention Name(s)
Erbitux, C225
Intervention Description
400mg/m2/week, 2 hours,iv,at week 1;250mg/m2/week,1hour,iv,at week 2-4
Primary Outcome Measure Information:
Title
Expression of Survivin protein in Esophageal Squamous Cell Carcinoma before and after Radiotherapy
Description
Survivin, an inhibitor of apoptosis protein, is highly expressed in most cancers and associated with radiotherapy resistance, increased tumor recurrence, and shorter patient survival.
Time Frame
before radiotherapy and 1 months after the radiotherapy
Title
Expression of p53 in Esophageal Squamous Cell Carcinoma before and after Radiotherapy
Description
p53 (also known as protein 53 or tumor protein 53), is a tumor suppressor protein that in humans is encoded by the TP53 gene.p53 is important in multicellular organisms and involved in preventing cancer.
Time Frame
before radiotherapy and 1 months after the radiotherapy
Title
changes of serum vascular endothelial growth factor(VEGF)level before and after radiotherapy
Description
Vascular endothelial growth factor (VEGF) is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis.
Time Frame
before radiotherapy and 1 months after the radiotherapy
Secondary Outcome Measure Information:
Title
Quality of life (QOL)
Description
Quality of life (QOL) as measured by European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30)
Time Frame
up to 3 years
Title
Overall survival
Description
time from randomization to death
Time Frame
up to 3 years
Title
PFS(progression-free survival)
Description
time from randomization to one of the following events, whichever comes first: Tumor progression at any time (progression of primary tumor or local lymph nodes, appearance of new lesions) Recurrence at local, regional or distant site after surgery Death from any cause
Time Frame
up to 3 years
Title
local control rate(LCR)
Description
Time to locoregional failure after R0 resection
Time Frame
up to 3 years
Title
Pathological remission
Time Frame
1 months after the end of surgery
Title
grade 3-5 adverse events
Description
Grade 3-5 adverse events as assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0,such as esophagitis、pneumonitis and hematologic toxicity
Time Frame
up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: (1)18 to 65 years old,male or female (2)Pathologically or cytologically proven thoracic middle-lower esophageal squamous cell carcinoma; (3)clinical stage II or stage III; (4)Primary tumors can be measured; (5)Karnofsky score >70; (6)Estimated life expectancy of at least 12 weeks; (7)reproductive age women should ensure that before entering the study period contraception; (8)Hemoglobin≥90.0g/dL,white blood cell count(WBC)≥ 4000 cells/mm³,Platelet count≥100,000 cells/mm³; (9)Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 times upper limit of normal,bilirubin normal; (10)Creatinine normal OR creatinine clearance ≥ 60 mL/min; (11)Patients have good compliance to treatment and follow-up of acceptance; (12)Forced expiratory volume in one second(FEV1) ≥ 1.5 litre or ≥ 75% of the reference value; (13)Considered operable (i.e. appropriate organ functions and ability to undergo general anesthesia); (14)No severe or uncontrolled cardiovascular disease; (15)No active uncontrolled infection; Exclusion Criteria: Patient who have distant metastasis The primary tumor or lymph node already received surgical treatment (except for biopsy); Patient who received radiotherapy for primary tumor or lymph node; Patient who received the the epidermal growth factor targeted therapy; Patient who received chemotherapy or immunotherapy; Patient who suffered from other malignant tumor; Epidermal growth factor receptor(EGFR)mutation(-); Patient who have taken other drug test within 1 month; Pregnant woman or Lactating Women and Women in productive age who refuse to take contraception in observation period; Subject with a severe allergic history or idiosyncratic; Subject with severe pulmonary and cardiopathic disease history; Refuse or incapable to sign the informed consent form of participating this trial; Drug abuse or alcohol addicted; Subject with a Personality or psychiatric diseases, people with no legal; capacity or people with limited capacity for civil conduct;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
TAO LI, MD, PhD
Phone
86-18908178818
Email
litaoxmf@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
YONGTAO HAN, MD, PhD
Organizational Affiliation
Sichuan Cancer Hospital & Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
GE WANG, MD, PhD
Organizational Affiliation
Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
TAIQIAN GONG, MD, PhD
Organizational Affiliation
Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
LONG CHEN, MD, PhD
Organizational Affiliation
Affiliated Cancer Hospital & Institute of Guangzhou Medical University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
NAIQUAN MAO, MD, PhD
Organizational Affiliation
Affiliated Cancer Hospital & Institute of Guangzhou Medical University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
ZHIHUA RUAN, MD, PhD
Organizational Affiliation
Southwest Hospital, China
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
GANG XIONG, MD, PhD
Organizational Affiliation
Southwest Hospital, China
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
JIANGUO SUN, MD, PhD
Organizational Affiliation
Xinqiao Hospital of Chongqing
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
GUANGHUI LI, MD.PHD
Organizational Affiliation
Xinqiao Hospital of Chongqing
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
DEZHI LI, MD, PhD
Organizational Affiliation
Xinqiao Hospital of Chongqing
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
MINGZHANG XIANG, MD,PhD
Organizational Affiliation
Xinqiao Hospital of Chongqing
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sichuan Cancer Hospital & Institute
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610041
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
TAO LI, MD, PhD
Phone
86-18908178818
Email
litaoxmf@163.com

12. IPD Sharing Statement

Learn more about this trial

Changes in Tumor Tissue and Serum Biomarkers Before and After Cetuximab Combined With Preoperative Radiotherapy in Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma

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