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

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

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.

Study Overview

• Status: Unknown
• Conditions: Locally Advanced Thoracic Middle-lower Segment Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Radiation: preoperative radiotherapy; Drug: cetuximab

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: TAO LI, MD, PhD; Phone Number: 86-18908178818; Email: litaoxmf@126.com

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • Sichuan Cancer Hospital & Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Arm A; 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.

Radiation: preoperative radiotherapy; 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.; Drug: cetuximab; 400mg/m2/week, 2 hours,iv,at week 1;250mg/m2/week,1hour,iv,at week 2-4; Other Names: C225; Erbitux

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	before radiotherapy and 1 months after the radiotherapy
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.	before radiotherapy and 1 months after the radiotherapy
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.	before radiotherapy and 1 months after the radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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）	up to 3 years
Overall survival	time from randomization to death	up to 3 years
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	up to 3 years
local control rate（LCR）	Time to locoregional failure after R0 resection	up to 3 years
Pathological remission		1 months after the end of surgery
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	up to 3 years

Collaborators and Investigators

• Sponsor: Sichuan Cancer Hospital and Research Institute
• Collaborators: Southwest Hospital, China; Affiliated Cancer Hospital & Institute of Guangzhou Medical University; Xinqiao Hospital of Chongqing; Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
• Investigators: Principal Investigator: YONGTAO HAN, MD, PhD, Sichuan Cancer Hospital & Institute; Principal Investigator: GE WANG, MD, PhD, Daping Hospital and the Research Institute of Surgery of the Third Military Medical University; Principal Investigator: TAIQIAN GONG, MD, PhD, Daping Hospital and the Research Institute of Surgery of the Third Military Medical University; Principal Investigator: LONG CHEN, MD, PhD, Affiliated Cancer Hospital & Institute of Guangzhou Medical University; Principal Investigator: NAIQUAN MAO, MD, PhD, Affiliated Cancer Hospital & Institute of Guangzhou Medical University; Principal Investigator: ZHIHUA RUAN, MD, PhD, Southwest Hospital, China; Principal Investigator: GANG XIONG, MD, PhD, Southwest Hospital, China; Principal Investigator: JIANGUO SUN, MD, PhD, Xinqiao Hospital of Chongqing; Principal Investigator: GUANGHUI LI, MD.PHD, Xinqiao Hospital of Chongqing; Principal Investigator: DEZHI LI, MD, PhD, Xinqiao Hospital of Chongqing; Principal Investigator: MINGZHANG XIANG, MD,PhD, Xinqiao Hospital of Chongqing

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (ANTICIPATED): July 1, 2020
• Study Completion (ANTICIPATED): July 1, 2020

Study Registration Dates

• First Submitted: April 13, 2014
• First Submitted That Met QC Criteria: April 23, 2014
• First Posted (ESTIMATE): April 25, 2014

Study Record Updates

• Last Update Posted (ACTUAL): March 17, 2020
• Last Update Submitted That Met QC Criteria: March 16, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: cetuximab; esophageal squamous cell carcinoma; preoperative radiotherapy; tumor tissue and serum biomarkers
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: scch2014019