Detection of Circulating Tumor Tells as The Guidance of the Neoadjuvant Chemotherapy of Esophageal Cancer

January 17, 2018 updated by: Xiaogang Zhao, The Second Hospital of Shandong University

Esophageal carcinoma is a common digestive system tumor, with number of deaths ranking No. 4 in malignant tumors. Esophageal squamous cell carcinoma in stage Ⅱ, III is the most common in China. The esophageal cancer during these stages is no longer localized lesions, and cancer will be transferred to other organs of the body through blood transmission, leading to tumor metastasis, which is the main cause of the patients' death. The tumor cells invade the surrounding tissues of primary tumor cells and enter the blood and lymphatic system, thus the circulating tumor cells (CTC) is formed and transported to a distal tissue, then effusing, adapting to the new microenvironment and finally forming metastases through the process of seeding, proliferation and colonization.

Recently, the controversy of surgical treatment of esophageal carcinoma is concentrated on the neoadjuvant therapy during perioperative period. NCCN guideline of 2015 recommended that patients with esophageal squamous cell carcinoma in T1b, N + and T2-T4a, N0-N + may consider preoperative neoadjuvant therapy, but its supporting literature (David Cunningham 2006, Marc Ychou 2011 and P. van Hagen, 2013) includes patients with pathology of the type adenocarcinoma. The esophageal cancer treatment guidelines of Japan 2015 adopted the opinion of NCCN Guidelines, and recommended neoadjuvant chemotherapy and radical surgery as the standard treatment for stage II and III esophageal cancer patients based on the results of randomized controlled clinical trial JCOG9907. However, the guidelines also pointed out that the role of neoadjuvant chemotherapy for resectable T1-3N0-1M0 cancers remains unclear according to the results of some meta-analysis.

The investigators choose the detection of peripheral venous blood CTCs and the disease-free survival as the main index, to compare the treatment effect of patients, those received neoadjuvant therapy, surgery and those received directly surgery, postoperative chemotherapy with esophageal squamous cell carcinoma in stage Ⅱ, III by means of evidence-based medicine; Define the indication of neoadjuvant chemotherapy in the treatment of esophageal squamous cell carcinoma in stage Ⅱ, III; Draft the solution to evaluate the treatment effect of neoadjuvant chemotherapy to esophageal cancer in stage Ⅱ, III, and the indication of neoadjuvant chemotherapy by test the peripheral venous blood CTCs and join the Chinese clinical guideline.

Study Overview

Detailed Description

Background Esophageal carcinoma is a common digestive system tumor, with number of deaths ranking No. 4 in malignant tumors. Surgery is the preferred method of treatment for esophageal cancer, but the local recurrence rate is as high as between 40% and 60%, and 5-year overall survival is only about 30%. Most of esophageal cancers are found in the middle and late stage, losing the chance of operation. Esophageal squamous cell carcinoma in stage Ⅱ, III is the most common in China. The esophageal cancer during these stages is no longer localized lesions, and cancer will be transferred to other organs of the body through blood transmission, leading to tumor metastasis, which is the main cause of the patients' death. The tumor cells invade the surrounding tissues of primary tumor cells and enter the blood and lymphatic system, thus the circulating tumor cells (CTC) is formed and transported to a distal tissue, then effusing, adapting to the new microenvironment and finally forming metastases through the process of seeding, proliferation and colonization. In recent years, as liquid pathology, CTCs are used for several studies of tumor, including the auxiliary diagnosis, recurrence and metastasis detection, prognosis, individualized treatment, medical screening, development of new targeted cancer therapy drugs, searching for a new target for cancer therapy, exploring the mechanism of drug resistance, etc.

Recently, the controversy of surgical treatment of esophageal carcinoma is concentrated on the neoadjuvant therapy during perioperative period. Neoadjuvant therapy has been widely studied in recent years. Compared to the postoperative radiochemotherapy,the preoperative chemotherapy is less toxic and better tolerated. Pure radiotherapy could only work on the local tumor, yet without lethal effect towards micrometastases and CTCs. Studies have shown that neoadjuvant radiotherapy can only improve the resection rate, but could not prolong the patient's survival; the advantages of neoadjuvant chemotherapy include: 1. lower tumor stage, reduce tumor volume , and increase the resection rate; 2. control and treat the tiny metastasis, reduce the recurrence rate; 3. chemotherapeutic drugs can reach to tumor issues with sufficient amount , through the undamaged blood supply system; 4. assess the chemosensitivity of drug in body to guide postoperative treatment.

NCCN guideline of 2015 recommended that patients with esophageal squamous cell carcinoma in T1b, N + and T2-T4a, N0-N + may consider preoperative neoadjuvant therapy, but its supporting literature (David Cunningham 2006, Marc Ychou 2011 and P. van Hagen, 2013) includes patients with pathology of the type adenocarcinoma. The esophageal cancer treatment guidelines of Japan 2015 adopted the opinion of NCCN Guidelines, and recommended neoadjuvant chemotherapy and radical surgery as the standard treatment for stage II and III esophageal cancer patients based on the results of randomized controlled clinical trial JCOG9907. However, the guidelines also pointed out that the role of neoadjuvant chemotherapy for resectable T1-3N0-1M0 cancers remains unclear according to the results of some meta-analysis. But at least for the present studies, compared to direct surgery group, the patients received neoadjuvant therapy did not show inferior effect at aspects such as radical surgery, postoperative complications, disease-free survival and overall survival.

The effect and necessity of neoadjuvant chemotherapy to esophageal squamous cell carcinoma patients in stage Ⅱ, Ⅲ, and its influence to disease-free survival still lack authoritative evidence-based medical support, is a clinical urgency need to be solved.

Research objectives Choose the detection of peripheral venous blood CTCs and the disease-free survival as the main index, to compare the treatment effect of patients, those received neoadjuvant therapy, surgery and those received directly surgery, postoperative chemotherapy with esophageal squamous cell carcinoma in stage Ⅱ, III by means of evidence-based medicine; Define the indication of neoadjuvant chemotherapy in the treatment of esophageal squamous cell carcinoma in stage Ⅱ, III; Draft the solution to evaluate the treatment effect of neoadjuvant chemotherapy to esophageal cancer in stage Ⅱ, III, and the indication of neoadjuvant chemotherapy by test the peripheral venous blood CTCs and join the Chinese clinical guideline.

Main research content:

Design dual-center (Second Hospital of Shandong University and Shandong Cancer Hospital Affiliated to Shandong University) prospective clinical contrast trials by selecting the preoperative patients with esophageal squamous cell carcinoma in clinical stage Ⅱ, III. Complete the work of patients screening, informed consent, preoperative preparation, surgery, neoadjuvant chemotherapy and follow-up visits under the guide of Standardized treatment program. Detect the CTCs by extract the peripheral venous blood at the time of the day before initial treatment (neoadjuvant chemotherapy or surgery), one week after surgery and the follow-up visits of 3 months, 6 months, 1 year, 2years after surgery. The main evaluation index of the study is the change of CTCs in peripheral blood and the survival period of disease-free of patients, with secondary evaluation index including the surgery effect, pathology, recurrence rate of the patients, long-term survival as well as other prognostic indicators. Assess the guidance of CTCs detection towards neoadjuvant chemotherapy in the treatment of esophageal squamous carcinoma in stage Ⅱ, III.

Study Type

Interventional

Enrollment (Anticipated)

120

Phase

  • Not Applicable

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

    • Shandong
      • Jinan, Shandong, China, 250033
        • Recruiting
        • The Second Hospital of Shandong University

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

35 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • histologically proven squamous cell carcinoma of the thoracic esophagus;clinical stage II or III excluding T4 disease
  • resectable disease; ECOG performance status of 0 to 2
  • no previous chemo- or radiotherapy for any malignancies
  • sufficient organ function.

Exclusion Criteria:

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: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Surgery
Postoperative chemotherapy group
chemotherapy after surgery
Other: Chemotherapy
Preoperative chemotherapy group
chemotherapy before surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
progression- free survival
Time Frame: through study completion, an average of 2-3 year
survival without recurrence or metastasis
through study completion, an average of 2-3 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
overall survival
Time Frame: through study completion, an average of 5 year
postoperation to death
through study completion, an average of 5 year

Collaborators and Investigators

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

Investigators

  • Principal Investigator: Xiaogang Zhao, Doctor, The Second Hospital of Shandong University

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

August 1, 2016

Primary Completion (Anticipated)

December 1, 2018

Study Completion (Anticipated)

December 1, 2019

Study Registration Dates

First Submitted

August 4, 2016

First Submitted That Met QC Criteria

December 24, 2016

First Posted (Estimate)

December 29, 2016

Study Record Updates

Last Update Posted (Actual)

January 18, 2018

Last Update Submitted That Met QC Criteria

January 17, 2018

Last Verified

January 1, 2018

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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