<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/NCT01670409</url>
  </required_header>
  <id_info>
    <org_study_id>SUMC-ECA-001</org_study_id>
    <secondary_id>ChiCTR-ONC-12002356</secondary_id>
    <nct_id>NCT01670409</nct_id>
  </id_info>
  <brief_title>Study of Simultaneous Modulated Accelerated Radiation Therapy Concurrent With Chemotherapy to Treat Esophageal Cancer</brief_title>
  <official_title>A Phase II Study of Simultaneous Modulated Accelerated Radiation Therapy Concurrent With Chemotherapy in Patients With Esophageal Squamous Cell Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chuangzhen Chen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shantou University Medical College</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the acute and 2-year late toxicities, the 2-year&#xD;
      local control and overall survival rates in patients with esophageal squamous cell carcinoma&#xD;
      receiving simultaneous modulated accelerated radiation therapy concurrent with chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Esophageal cancer is one of the most common malignant diseases in China, especially in&#xD;
      Chaoshan region. Concurrent chemoradiotherapy is the standard non-surgical treatment method&#xD;
      for this disease and the radiation schedule is about 50.4~60 Gray (Gy) in total, 1.8~2Gy per&#xD;
      fraction generally. However, although with such comprehensive method, noncontrol of local&#xD;
      disease or recurrence is still the main reason of failure.&#xD;
&#xD;
      Most patients with esophageal cancer suffer from malnutrition. A number of factors including&#xD;
      hypoxic, inflammation, radioresistance and accelerated repopulation may contribute to local&#xD;
      failures of disease after treatment; therefore a higher radiation biological equivalent dose&#xD;
      (BED) will improve the local control probability. Although the intergroup 0123 (INT123) trial&#xD;
      had shown that simply increasing total radiation dose could not gain better local control or&#xD;
      overall survival rate, however, the ability of this trial to test the potential benefits of&#xD;
      higher radiation dose could be compromized by the deficiencies within them, such as,&#xD;
      observation bias,large radiated target volume and usage of conventional radiation technique.&#xD;
      In other words, the probability that increasing radiation may help improving the control of&#xD;
      disease should not be denied.&#xD;
&#xD;
      Modern radiation techniques, such as intensity modulation radiation therapy (IMRT),&#xD;
      specially, are able to improve the coverage of target volumes and sparing of critical&#xD;
      structures, while increase the total radiation dose. By using simultaneous modulated&#xD;
      accelerated radiation therapy (SMART) technique, the doses to the relevant normal organs per&#xD;
      fraction could be reduced significantly, while the doses to tumor could be increased to&#xD;
      higher than 2Gy. Thus reach the double goal of protection of normal tissues, increasing total&#xD;
      radiation Equivalent Uniform Dose (EUD). Dosimetric study has proven the feasibility and&#xD;
      superiority of SMART-base IMRT in radiation treatment of esophageal cancer, compared with&#xD;
      conventional technique.&#xD;
&#xD;
      Overall, SMART-base IMRT concurrent with chemotherapy may improve the local control and&#xD;
      overall survival rate of patients with esophageal cancer; Meanwhile, the acute and late&#xD;
      toxicities would be tolerable and slighter than that of conventional technique.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">August 2015</completion_date>
  <primary_completion_date type="Actual">August 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Toxicities</measure>
    <time_frame>The period during treatment and the 2 years after treatment</time_frame>
    <description>The probabilities of grade ≥ 3 acute toxicities and 2-year late toxicities of esophagus and lungs as assessed by CTCAE 4.0</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Local control rate</measure>
    <time_frame>2 years after treatment</time_frame>
    <description>The percentage of patients without locoregional tumor recurrence 2 years after treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall survival rate</measure>
    <time_frame>2 years after treatment</time_frame>
    <description>The percentage of patients that are alive 2 years after treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complete blood count</measure>
    <time_frame>before radiation treatment and after every 5 fraction of radiotherapy (7 time points in total)</time_frame>
    <description>The complete blood count as assessed by a Coulter (LH 750 Haematology Analyzer)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">85</enrollment>
  <condition>Esophageal Neoplasms</condition>
  <arm_group>
    <arm_group_label>SMART combined with PF chemotherpay</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SMART-base IMRT with concurrent and adjuvant chemotherapy(cisplatin and 5-fluorouracil)</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>SMART</intervention_name>
    <description>The PTV (planning target volume) of gross tumor will receive radiation dose of 66Gy, 2.2Gy per fraction and the PTV of subclinical disease will receive 54Gy, 1.8Gy per fraction,5 fraction per week.</description>
    <arm_group_label>SMART combined with PF chemotherpay</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PF</intervention_name>
    <description>Concurrent and adjuvant chemotherapy: Cisplatin, 80mg/m2, intravenous on day 1, 5fluorouracil 0.5/m2, intravenous on d1 to d4. Two cycles during radiation treatment on d1 and d28. Two additional cycles after radiation treatment, 4 weeks per cycle.</description>
    <arm_group_label>SMART combined with PF chemotherpay</arm_group_label>
    <other_name>cisplatin plus 5fluorouracil</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  pathological proven diagnosis of primary squamous cell carcinoma of the esophagus&#xD;
&#xD;
          -  the primary disease located in cervical, upper or middle thoracic esophagus&#xD;
&#xD;
          -  no distant metastases&#xD;
&#xD;
          -  zubrod performance status: 0~2&#xD;
&#xD;
          -  life expectancy &gt; 6 months; -absence of another malignancy&#xD;
&#xD;
          -  adequate liver, renal and bone marrow function&#xD;
&#xD;
          -  women of childbearing potential and male participants must practice adequate&#xD;
             contraception&#xD;
&#xD;
          -  patient must provide study-specific informed consent prior to study entry&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  evidence of tracheoesophageal or Mediastinal-esophageal fistula&#xD;
&#xD;
          -  prior invasive malignancy (except non-melanomatous skin cancer) unless disease free&#xD;
             for a minimum of 2 years&#xD;
&#xD;
          -  prior radiation therapy that would result in overlap of planned radiation therapy&#xD;
             fields; - Severe, active comorbidity&#xD;
&#xD;
          -  pregnancy or women of childbearing potential and men who are sexually active and not&#xD;
             willing/able to use medically acceptable forms of contraception&#xD;
&#xD;
          -  women who are nursing&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chuangzhen Chen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cancer Hospital, Shantou University Medical College</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cancer Hospital, Shantou University Medical College</name>
      <address>
        <city>Shantou</city>
        <state>Guangdong</state>
        <zip>515031</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>August 12, 2012</study_first_submitted>
  <study_first_submitted_qc>August 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 22, 2012</study_first_posted>
  <last_update_submitted>December 27, 2021</last_update_submitted>
  <last_update_submitted_qc>December 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 3, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Shantou University Medical College</investigator_affiliation>
    <investigator_full_name>Chuangzhen Chen</investigator_full_name>
    <investigator_title>M.D.</investigator_title>
  </responsible_party>
  <keyword>Esophageal squamous cell carcinoma</keyword>
  <keyword>SMART</keyword>
  <keyword>IMRT</keyword>
  <keyword>Chemotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Esophageal Squamous Cell Carcinoma</mesh_term>
    <mesh_term>Esophageal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cisplatin</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01670409
org study id: SUMC-ECA-001
secondary id: ChiCTR-ONC-12002356
nct id: NCT01670409
lead sponsor: 
has dmc: No
The purpose of this study is to evaluate the acute and 2-year late toxicities, the 2-year
      local control and overall survival rates in patients with esophageal squamous cell carcinoma
      receiving simultaneous modulated accelerated radiation therapy concurrent with chemotherapy.
Esophageal cancer is one of the most common malignant diseases in China, especially in
      Chaoshan region. Concurrent chemoradiotherapy is the standard non-surgical treatment method
      for this disease and the radiation schedule is about 50.4~60 Gray (Gy) in total, 1.8~2Gy per
      fraction generally. However, although with such comprehensive method, noncontrol of local
      disease or recurrence is still the main reason of failure.

      Most patients with esophageal cancer suffer from malnutrition. A number of factors including
      hypoxic, inflammation, radioresistance and accelerated repopulation may contribute to local
      failures of disease after treatment; therefore a higher radiation biological equivalent dose
      (BED) will improve the local control probability. Although the intergroup 0123 (INT123) trial
      had shown that simply increasing total radiation dose could not gain better local control or
      overall survival rate, however, the ability of this trial to test the potential benefits of
      higher radiation dose could be compromized by the deficiencies within them, such as,
      observation bias,large radiated target volume and usage of conventional radiation technique.
      In other words, the probability that increasing radiation may help improving the control of
      disease should not be denied.

      Modern radiation techniques, such as intensity modulation radiation therapy (IMRT),
      specially, are able to improve the coverage of target volumes and sparing of critical
      structures, while increase the total radiation dose. By using simultaneous modulated
      accelerated radiation therapy (SMART) technique, the doses to the relevant normal organs per
      fraction could be reduced significantly, while the doses to tumor could be increased to
      higher than 2Gy. Thus reach the double goal of protection of normal tissues, increasing total
      radiation Equivalent Uniform Dose (EUD). Dosimetric study has proven the feasibility and
      superiority of SMART-base IMRT in radiation treatment of esophageal cancer, compared with
      conventional technique.

      Overall, SMART-base IMRT concurrent with chemotherapy may improve the local control and
      overall survival rate of patients with esophageal cancer; Meanwhile, the acute and late
      toxicities would be tolerable and slighter than that of conventional technique.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Toxicities
time frame: The period during treatment and the 2 years after treatment
description: The probabilities of grade ≥ 3 acute toxicities and 2-year late toxicities of esophagus and lungs as assessed by CTCAE 4.0
measure: Local control rate
time frame: 2 years after treatment
description: The percentage of patients without locoregional tumor recurrence 2 years after treatment
measure: overall survival rate
time frame: 2 years after treatment
description: The percentage of patients that are alive 2 years after treatment
measure: Complete blood count
time frame: before radiation treatment and after every 5 fraction of radiotherapy (7 time points in total)
description: The complete blood count as assessed by a Coulter (LH 750 Haematology Analyzer)
arm group label: SMART combined with PF chemotherpay
arm group type: Experimental
description: SMART-base IMRT with concurrent and adjuvant chemotherapy(cisplatin and 5-fluorouracil)
intervention type: Radiation
intervention name: SMART
description: The PTV (planning target volume) of gross tumor will receive radiation dose of 66Gy, 2.2Gy per fraction and the PTV of subclinical disease will receive 54Gy, 1.8Gy per fraction,5 fraction per week.
arm group label: SMART combined with PF chemotherpay
intervention type: Drug
intervention name: PF
description: Concurrent and adjuvant chemotherapy: Cisplatin, 80mg/m2, intravenous on day 1, 5fluorouracil 0.5/m2, intravenous on d1 to d4. Two cycles during radiation treatment on d1 and d28. Two additional cycles after radiation treatment, 4 weeks per cycle.
arm group label: SMART combined with PF chemotherpay
other name: cisplatin plus 5fluorouracil
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Chuangzhen Chen, MD
role: Principal Investigator
affiliation: Cancer Hospital, Shantou University Medical College
facility: 
country: China
responsible party type: Sponsor-Investigator
investigator affiliation: Shantou University Medical College
investigator full name: Chuangzhen Chen
investigator title: M.D.
mesh term: Esophageal Squamous Cell Carcinoma
mesh term: Esophageal Neoplasms
mesh term: Cisplatin
mesh term: Fluorouracil