<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03005314</url>
  </required_header>
  <id_info>
    <org_study_id>2016YFC0106005</org_study_id>
    <nct_id>NCT03005314</nct_id>
  </id_info>
  <brief_title>Detection of Circulating Tumor Tells as The Guidance of the Neoadjuvant Chemotherapy of Esophageal Cancer</brief_title>
  <official_title>Detection of Circulating Tumor Tells as The Guidance of the Neoadjuvant Chemotherapy of Esophageal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Second Hospital of Shandong University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Shandong Cancer Hospital and Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Wuhan YZY Medical Science and Technology Co., Ltd.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The Second Hospital of Shandong University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Esophageal carcinoma is a common digestive system tumor, with number of deaths ranking No. 4&#xD;
      in malignant tumors. Esophageal squamous cell carcinoma in stage Ⅱ, III is the most common in&#xD;
      China. The esophageal cancer during these stages is no longer localized lesions, and cancer&#xD;
      will be transferred to other organs of the body through blood transmission, leading to tumor&#xD;
      metastasis, which is the main cause of the patients' death. The tumor cells invade the&#xD;
      surrounding tissues of primary tumor cells and enter the blood and lymphatic system, thus the&#xD;
      circulating tumor cells (CTC) is formed and transported to a distal tissue, then effusing,&#xD;
      adapting to the new microenvironment and finally forming metastases through the process of&#xD;
      seeding, proliferation and colonization.&#xD;
&#xD;
      Recently, the controversy of surgical treatment of esophageal carcinoma is concentrated on&#xD;
      the neoadjuvant therapy during perioperative period. NCCN guideline of 2015 recommended that&#xD;
      patients with esophageal squamous cell carcinoma in T1b, N + and T2-T4a, N0-N + may consider&#xD;
      preoperative neoadjuvant therapy, but its supporting literature (David Cunningham 2006, Marc&#xD;
      Ychou 2011 and P. van Hagen, 2013) includes patients with pathology of the type&#xD;
      adenocarcinoma. The esophageal cancer treatment guidelines of Japan 2015 adopted the opinion&#xD;
      of NCCN Guidelines, and recommended neoadjuvant chemotherapy and radical surgery as the&#xD;
      standard treatment for stage II and III esophageal cancer patients based on the results of&#xD;
      randomized controlled clinical trial JCOG9907. However, the guidelines also pointed out that&#xD;
      the role of neoadjuvant chemotherapy for resectable T1-3N0-1M0 cancers remains unclear&#xD;
      according to the results of some meta-analysis.&#xD;
&#xD;
      The investigators choose the detection of peripheral venous blood CTCs and the disease-free&#xD;
      survival as the main index, to compare the treatment effect of patients, those received&#xD;
      neoadjuvant therapy, surgery and those received directly surgery, postoperative chemotherapy&#xD;
      with esophageal squamous cell carcinoma in stage Ⅱ, III by means of evidence-based medicine;&#xD;
      Define the indication of neoadjuvant chemotherapy in the treatment of esophageal squamous&#xD;
      cell carcinoma in stage Ⅱ, III; Draft the solution to evaluate the treatment effect of&#xD;
      neoadjuvant chemotherapy to esophageal cancer in stage Ⅱ, III, and the indication of&#xD;
      neoadjuvant chemotherapy by test the peripheral venous blood CTCs and join the Chinese&#xD;
      clinical guideline.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background Esophageal carcinoma is a common digestive system tumor, with number of deaths&#xD;
      ranking No. 4 in malignant tumors. Surgery is the preferred method of treatment for&#xD;
      esophageal cancer, but the local recurrence rate is as high as between 40% and 60%, and&#xD;
      5-year overall survival is only about 30%. Most of esophageal cancers are found in the middle&#xD;
      and late stage, losing the chance of operation. Esophageal squamous cell carcinoma in stage&#xD;
      Ⅱ, III is the most common in China. The esophageal cancer during these stages is no longer&#xD;
      localized lesions, and cancer will be transferred to other organs of the body through blood&#xD;
      transmission, leading to tumor metastasis, which is the main cause of the patients' death.&#xD;
      The tumor cells invade the surrounding tissues of primary tumor cells and enter the blood and&#xD;
      lymphatic system, thus the circulating tumor cells (CTC) is formed and transported to a&#xD;
      distal tissue, then effusing, adapting to the new microenvironment and finally forming&#xD;
      metastases through the process of seeding, proliferation and colonization. In recent years,&#xD;
      as liquid pathology, CTCs are used for several studies of tumor, including the auxiliary&#xD;
      diagnosis, recurrence and metastasis detection, prognosis, individualized treatment, medical&#xD;
      screening, development of new targeted cancer therapy drugs, searching for a new target for&#xD;
      cancer therapy, exploring the mechanism of drug resistance, etc.&#xD;
&#xD;
      Recently, the controversy of surgical treatment of esophageal carcinoma is concentrated on&#xD;
      the neoadjuvant therapy during perioperative period. Neoadjuvant therapy has been widely&#xD;
      studied in recent years. Compared to the postoperative radiochemotherapy,the preoperative&#xD;
      chemotherapy is less toxic and better tolerated. Pure radiotherapy could only work on the&#xD;
      local tumor, yet without lethal effect towards micrometastases and CTCs. Studies have shown&#xD;
      that neoadjuvant radiotherapy can only improve the resection rate, but could not prolong the&#xD;
      patient's survival; the advantages of neoadjuvant chemotherapy include: 1. lower tumor stage,&#xD;
      reduce tumor volume , and increase the resection rate; 2. control and treat the tiny&#xD;
      metastasis, reduce the recurrence rate; 3. chemotherapeutic drugs can reach to tumor issues&#xD;
      with sufficient amount , through the undamaged blood supply system; 4. assess the&#xD;
      chemosensitivity of drug in body to guide postoperative treatment.&#xD;
&#xD;
      NCCN guideline of 2015 recommended that patients with esophageal squamous cell carcinoma in&#xD;
      T1b, N + and T2-T4a, N0-N + may consider preoperative neoadjuvant therapy, but its supporting&#xD;
      literature (David Cunningham 2006, Marc Ychou 2011 and P. van Hagen, 2013) includes patients&#xD;
      with pathology of the type adenocarcinoma. The esophageal cancer treatment guidelines of&#xD;
      Japan 2015 adopted the opinion of NCCN Guidelines, and recommended neoadjuvant chemotherapy&#xD;
      and radical surgery as the standard treatment for stage II and III esophageal cancer patients&#xD;
      based on the results of randomized controlled clinical trial JCOG9907. However, the&#xD;
      guidelines also pointed out that the role of neoadjuvant chemotherapy for resectable&#xD;
      T1-3N0-1M0 cancers remains unclear according to the results of some meta-analysis. But at&#xD;
      least for the present studies, compared to direct surgery group, the patients received&#xD;
      neoadjuvant therapy did not show inferior effect at aspects such as radical surgery,&#xD;
      postoperative complications, disease-free survival and overall survival.&#xD;
&#xD;
      The effect and necessity of neoadjuvant chemotherapy to esophageal squamous cell carcinoma&#xD;
      patients in stage Ⅱ, Ⅲ, and its influence to disease-free survival still lack authoritative&#xD;
      evidence-based medical support, is a clinical urgency need to be solved.&#xD;
&#xD;
      Research objectives Choose the detection of peripheral venous blood CTCs and the disease-free&#xD;
      survival as the main index, to compare the treatment effect of patients, those received&#xD;
      neoadjuvant therapy, surgery and those received directly surgery, postoperative chemotherapy&#xD;
      with esophageal squamous cell carcinoma in stage Ⅱ, III by means of evidence-based medicine;&#xD;
      Define the indication of neoadjuvant chemotherapy in the treatment of esophageal squamous&#xD;
      cell carcinoma in stage Ⅱ, III; Draft the solution to evaluate the treatment effect of&#xD;
      neoadjuvant chemotherapy to esophageal cancer in stage Ⅱ, III, and the indication of&#xD;
      neoadjuvant chemotherapy by test the peripheral venous blood CTCs and join the Chinese&#xD;
      clinical guideline.&#xD;
&#xD;
      Main research content:&#xD;
&#xD;
      Design dual-center (Second Hospital of Shandong University and Shandong Cancer Hospital&#xD;
      Affiliated to Shandong University) prospective clinical contrast trials by selecting the&#xD;
      preoperative patients with esophageal squamous cell carcinoma in clinical stage Ⅱ, III.&#xD;
      Complete the work of patients screening, informed consent, preoperative preparation, surgery,&#xD;
      neoadjuvant chemotherapy and follow-up visits under the guide of Standardized treatment&#xD;
      program. Detect the CTCs by extract the peripheral venous blood at the time of the day before&#xD;
      initial treatment (neoadjuvant chemotherapy or surgery), one week after surgery and the&#xD;
      follow-up visits of 3 months, 6 months, 1 year, 2years after surgery. The main evaluation&#xD;
      index of the study is the change of CTCs in peripheral blood and the survival period of&#xD;
      disease-free of patients, with secondary evaluation index including the surgery effect,&#xD;
      pathology, recurrence rate of the patients, long-term survival as well as other prognostic&#xD;
      indicators. Assess the guidance of CTCs detection towards neoadjuvant chemotherapy in the&#xD;
      treatment of esophageal squamous carcinoma in stage Ⅱ, III.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>August 2016</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">December 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>progression- free survival</measure>
    <time_frame>through study completion, an average of 2-3 year</time_frame>
    <description>survival without recurrence or metastasis</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>overall survival</measure>
    <time_frame>through study completion, an average of 5 year</time_frame>
    <description>postoperation to death</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Esophageal Cancer TNM Staging Primary Tumor (T) T3</condition>
  <arm_group>
    <arm_group_label>Surgery</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Postoperative chemotherapy group</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Chemotherapy</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Preoperative chemotherapy group</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>chemotherapy</intervention_name>
    <description>chemotherapy before surgery</description>
    <arm_group_label>Chemotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Surgery</intervention_name>
    <description>chemotherapy after surgery</description>
    <arm_group_label>Surgery</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  histologically proven squamous cell carcinoma of the thoracic esophagus;clinical stage&#xD;
             II or III excluding T4 disease&#xD;
&#xD;
          -  resectable disease; ECOG performance status of 0 to 2&#xD;
&#xD;
          -  no previous chemo- or radiotherapy for any malignancies&#xD;
&#xD;
          -  sufficient organ function.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Xiaogang Zhao, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Second Hospital of Shandong University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Yunpeng Zhao, doctor</last_name>
    <phone>+8618766188692</phone>
    <email>zyp_baggio@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>The Second Hospital of Shandong University</name>
      <address>
        <city>Jinan</city>
        <state>Shandong</state>
        <zip>250033</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yunpeng Zhao, doctor</last_name>
      <phone>+8618766188692</phone>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>August 4, 2016</study_first_submitted>
  <study_first_submitted_qc>December 24, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 29, 2016</study_first_posted>
  <last_update_submitted>January 17, 2018</last_update_submitted>
  <last_update_submitted_qc>January 17, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Second Hospital of Shandong University</investigator_affiliation>
    <investigator_full_name>Xiaogang Zhao</investigator_full_name>
    <investigator_title>vice- director</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Esophageal Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03005314
org study id: 2016YFC0106005
nct id: NCT03005314
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: progression- free survival
time frame: through study completion, an average of 2-3 year
description: survival without recurrence or metastasis
measure: overall survival
time frame: through study completion, an average of 5 year
description: postoperation to death
arm group label: Surgery
arm group type: Other
description: Postoperative chemotherapy group
arm group label: Chemotherapy
arm group type: Other
description: Preoperative chemotherapy group
intervention type: Procedure
intervention name: chemotherapy
description: chemotherapy before surgery
arm group label: Chemotherapy
intervention type: Procedure
intervention name: Surgery
description: chemotherapy after surgery
arm group label: Surgery
criteria: 
gender: All
minimum age: 35 Years
maximum age: 80 Years
healthy volunteers: No
last name: Xiaogang Zhao, Doctor
role: Principal Investigator
affiliation: The Second Hospital of Shandong University
last name: Yunpeng Zhao, doctor
phone: +8618766188692
email: zyp_baggio@163.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: The Second Hospital of Shandong University
investigator full name: Xiaogang Zhao
investigator title: vice- director
mesh term: Esophageal Neoplasms
sharing ipd: No