<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/NCT02969122</url>
  </required_header>
  <id_info>
    <org_study_id>2016YJZ35</org_study_id>
    <nct_id>NCT02969122</nct_id>
  </id_info>
  <brief_title>Treatment Strategy for Stage IV Gastric Cancer With Positive Peritoneal Cytology as the Only Non-curable Factor</brief_title>
  <acronym>Cy-plus</acronym>
  <official_title>Treatment Strategy for Stage IV Gastric Cancer With Positive Peritoneal Cytology as the Only Non-curable Factor (Cy-plus): a Phase 2, Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Peking University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Gastric cancer with positive is defined as stage IV disease in 7th AJCC/UICC TNM staging&#xD;
      system. Controversy exists on the treatment of this part of patients. This trial aimed to&#xD;
      explore the optimal treatment strategy for stage IV gastric cancer with positive peritoneal&#xD;
      cytology as the only non-curable factor.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In the 7th AJCC/UICC TNM staging system, gastric cancer with positive peritoneal cytology&#xD;
      (CY+) is defined as stage IV disease. In NCCN clinical practice guidelines, it is suggested&#xD;
      that positive peritoneal cytology in the absence of visible peritoneal implants should be&#xD;
      considered as M1 disease and surgery as initial treatment is not recommended for patients&#xD;
      with positive peritoneal cytology. However, in the Japanese gastric cancer treatment&#xD;
      guidelines 2014, it is suggested that standard gastrectomy can be proposed for patients with&#xD;
      no other non-curative factors and if the CY+ status was revealed after surgery, postoperative&#xD;
      treatment with S-1 can be recommended as the tentative standard. Previous studies have also&#xD;
      proved that extensive intraperitoneal lavage(EIPL) and Hyperthermic Intraperitoneal&#xD;
      Chemotherapy(HIPEC) are effective methods for the treatment of peritoneal metastasis.&#xD;
&#xD;
      In order to optimize the treatment strategy of this part of patients, this trial is designed&#xD;
      to compare the effectiveness of 2 treatment strategies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date>November 2016</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall survival</measure>
    <time_frame>3 year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>peritoneal recurrence rate</measure>
    <time_frame>3 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recurrence free survival</measure>
    <time_frame>3 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>rate of peritoneal cytology converted to negative</measure>
    <time_frame>7 days After the second time laparoscopic staging and peritoneal cytology examination</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>morbidity and mortality of HIPEC and EIPL</measure>
    <time_frame>30 days after HIPEC and EIPL procedures</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">59</enrollment>
  <condition>Stomach Neoplasm</condition>
  <arm_group>
    <arm_group_label>Chemotherapy-first</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will receive hyperthermic intraperitoneal chemotherapy (HIPEC) during laparoscopic staging. Then 3 cycles of preoperative chemotherapy and clinical evaluation of chemotherapy will be performed. If the patient's disease is evaluated as progressed, the patient will receive systemic therapy. If it's stable or remission, a second time laparoscopic staging and peritoneal cytology examination will be performed. If peritoneal implant is observed, the patients will receive systemic therapy. If the peritoneal cytology is still positive, the treatment will be decided according to the suggestion of MDT discussion. If the peritoneal cytology is converted negative, standard gastrectomy with D2 lymphadenectomy and extensive intraperitoneal lavage (EIPL) will be performed. Postoperative chemotherapy will be determined according to the pathological evaluation of preoperative chemotherapy response.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Surgery-first</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients in this arm will receive standard gastrectomy with D2 lymphadenectomy after randomization. Hyperthermic intraperitoneal chemotherapy (HIPEC) and extensive intraperitoneal lavage (EIPL) will be applied before abdominal closure. After surgery, 8 cycles of postoperative chemotherapy will be performed.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>standard gastrectomy with D2 lymphadenectomy</intervention_name>
    <description>standard distal or total gastrectomy and accorded D2 lymphadenectomy</description>
    <arm_group_label>Chemotherapy-first</arm_group_label>
    <arm_group_label>Surgery-first</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>hyperthermic intraperitoneal chemotherapy</intervention_name>
    <description>Intraperitoneal docetaxel of 100mg/m2 at 42℃ for 30 minutes</description>
    <arm_group_label>Chemotherapy-first</arm_group_label>
    <arm_group_label>Surgery-first</arm_group_label>
    <other_name>HIPEC</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Extensive intraperitoneal lavage</intervention_name>
    <description>Lavage of peritoneal cavity with 1000ml saline for 10 times</description>
    <arm_group_label>Chemotherapy-first</arm_group_label>
    <arm_group_label>Surgery-first</arm_group_label>
    <other_name>EIPL</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Preoperative chemotherapy</intervention_name>
    <description>Oxaliplatin 130mg/m2 D1 S-1 40-60mg Bid D1-14 Repeated every 3 weeks.</description>
    <arm_group_label>Chemotherapy-first</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Postoperative chemotherapy</intervention_name>
    <description>SOX regimen postoperative chemotherapy (Oxaliplatin 130mg/m2 D1, S-1 40-60mg Bid D1-14, Repeated every 3 weeks) for surgery-first arm. Regimen for chemotherapy-first arm is determined according to the postoperative pathologic evaluation of response.</description>
    <arm_group_label>Chemotherapy-first</arm_group_label>
    <arm_group_label>Surgery-first</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pathologically diagnosed gastric adenocarcinoma with endoscopic biopsy;&#xD;
&#xD;
          -  Pretreatment clinical stage with computed tomography and/or endoscopic&#xD;
             ultrasonography;&#xD;
&#xD;
          -  Clinical stage cT2-4 N0-3 M0;&#xD;
&#xD;
          -  Standard gastrectomy with D2 lymphadenectomy is needed according to the clinicians'&#xD;
             evaluation;&#xD;
&#xD;
          -  ECOG performance score ≤2, with tolerance of standard gastrectomy and D2&#xD;
             lymphadenectomy;&#xD;
&#xD;
          -  Positive peritoneal cytology;&#xD;
&#xD;
          -  Signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Remnant gastric cancer, recurrence gastric cancer or multi-primary cancers;&#xD;
&#xD;
          -  Intraoperative identified other unresectable factors including other metastasis except&#xD;
             positive peritoneal cytology;&#xD;
&#xD;
          -  Postoperative pathologically diagnosed as non adenocarcinoma;&#xD;
&#xD;
          -  Pregnant or lactate women;&#xD;
&#xD;
          -  Child-bearing period adults who refuse to birth control during the trial;&#xD;
&#xD;
          -  Uncontrolled epilepsy, CNS disease or mental disorder that may influence the&#xD;
             compliance of the patient;&#xD;
&#xD;
          -  Severe/active heart disease, including but not limited to acute coronary syndrome,&#xD;
             congestive heart failure with less than NYHA II cardiac function, severe arrhythmia&#xD;
             that needs drug control, cardiac infarction within 12 month;&#xD;
&#xD;
          -  Organ transplantation patients who needs immune suppression therapy;&#xD;
&#xD;
          -  Patients who needs emergency surgery because of bleeding, perforation or obstruction.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jiafu Ji, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking University Cancer Hospital &amp; Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Rulin Miao, M.D.</last_name>
    <phone>86-10-88196598</phone>
    <email>miaorulin@outlook.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Gastrointestinal Cancer Center, Peking University Cancer Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100142</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rulin Miao, M.D.</last_name>
      <phone>86-10-88196598</phone>
      <email>miaorulin@outlook.com</email>
    </contact>
    <investigator>
      <last_name>Jiafu Ji, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ziyu Li, M.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Rulin Miao, M.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>November 12, 2016</study_first_submitted>
  <study_first_submitted_qc>November 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2016</study_first_posted>
  <last_update_submitted>November 23, 2016</last_update_submitted>
  <last_update_submitted_qc>November 23, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 28, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Peking University</investigator_affiliation>
    <investigator_full_name>Jiafu Ji</investigator_full_name>
    <investigator_title>President of Peking University Cancer Hospital</investigator_title>
  </responsible_party>
  <keyword>gastric cancer</keyword>
  <keyword>peritoneal cytology</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stomach 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/NCT02969122
org study id: 2016YJZ35
nct id: NCT02969122
lead sponsor: 
has dmc: No
Gastric cancer with positive is defined as stage IV disease in 7th AJCC/UICC TNM staging
      system. Controversy exists on the treatment of this part of patients. This trial aimed to
      explore the optimal treatment strategy for stage IV gastric cancer with positive peritoneal
      cytology as the only non-curable factor.
In the 7th AJCC/UICC TNM staging system, gastric cancer with positive peritoneal cytology
      (CY+) is defined as stage IV disease. In NCCN clinical practice guidelines, it is suggested
      that positive peritoneal cytology in the absence of visible peritoneal implants should be
      considered as M1 disease and surgery as initial treatment is not recommended for patients
      with positive peritoneal cytology. However, in the Japanese gastric cancer treatment
      guidelines 2014, it is suggested that standard gastrectomy can be proposed for patients with
      no other non-curative factors and if the CY+ status was revealed after surgery, postoperative
      treatment with S-1 can be recommended as the tentative standard. Previous studies have also
      proved that extensive intraperitoneal lavage(EIPL) and Hyperthermic Intraperitoneal
      Chemotherapy(HIPEC) are effective methods for the treatment of peritoneal metastasis.

      In order to optimize the treatment strategy of this part of patients, this trial is designed
      to compare the effectiveness of 2 treatment strategies.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall survival
time frame: 3 year
measure: peritoneal recurrence rate
time frame: 3 year
measure: Recurrence free survival
time frame: 3 year
measure: rate of peritoneal cytology converted to negative
time frame: 7 days After the second time laparoscopic staging and peritoneal cytology examination
measure: morbidity and mortality of HIPEC and EIPL
time frame: 30 days after HIPEC and EIPL procedures
arm group label: Chemotherapy-first
arm group type: Active Comparator
description: Patients will receive hyperthermic intraperitoneal chemotherapy (HIPEC) during laparoscopic staging. Then 3 cycles of preoperative chemotherapy and clinical evaluation of chemotherapy will be performed. If the patient's disease is evaluated as progressed, the patient will receive systemic therapy. If it's stable or remission, a second time laparoscopic staging and peritoneal cytology examination will be performed. If peritoneal implant is observed, the patients will receive systemic therapy. If the peritoneal cytology is still positive, the treatment will be decided according to the suggestion of MDT discussion. If the peritoneal cytology is converted negative, standard gastrectomy with D2 lymphadenectomy and extensive intraperitoneal lavage (EIPL) will be performed. Postoperative chemotherapy will be determined according to the pathological evaluation of preoperative chemotherapy response.
arm group label: Surgery-first
arm group type: Experimental
description: Patients in this arm will receive standard gastrectomy with D2 lymphadenectomy after randomization. Hyperthermic intraperitoneal chemotherapy (HIPEC) and extensive intraperitoneal lavage (EIPL) will be applied before abdominal closure. After surgery, 8 cycles of postoperative chemotherapy will be performed.
intervention type: Procedure
intervention name: standard gastrectomy with D2 lymphadenectomy
description: standard distal or total gastrectomy and accorded D2 lymphadenectomy
arm group label: Chemotherapy-first
arm group label: Surgery-first
intervention type: Procedure
intervention name: hyperthermic intraperitoneal chemotherapy
description: Intraperitoneal docetaxel of 100mg/m2 at 42℃ for 30 minutes
arm group label: Chemotherapy-first
arm group label: Surgery-first
other name: HIPEC
intervention type: Procedure
intervention name: Extensive intraperitoneal lavage
description: Lavage of peritoneal cavity with 1000ml saline for 10 times
arm group label: Chemotherapy-first
arm group label: Surgery-first
other name: EIPL
intervention type: Other
intervention name: Preoperative chemotherapy
description: Oxaliplatin 130mg/m2 D1 S-1 40-60mg Bid D1-14 Repeated every 3 weeks.
arm group label: Chemotherapy-first
intervention type: Other
intervention name: Postoperative chemotherapy
description: SOX regimen postoperative chemotherapy (Oxaliplatin 130mg/m2 D1, S-1 40-60mg Bid D1-14, Repeated every 3 weeks) for surgery-first arm. Regimen for chemotherapy-first arm is determined according to the postoperative pathologic evaluation of response.
arm group label: Chemotherapy-first
arm group label: Surgery-first
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Jiafu Ji, M.D.
role: Principal Investigator
affiliation: Peking University Cancer Hospital & Institute
last name: Rulin Miao, M.D.
phone: 86-10-88196598
email: miaorulin@outlook.com
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Peking University
investigator full name: Jiafu Ji
investigator title: President of Peking University Cancer Hospital
mesh term: Stomach Neoplasms
sharing ipd: No