<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/NCT03023436</url>
  </required_header>
  <id_info>
    <org_study_id>CLASS - 05</org_study_id>
    <nct_id>NCT03023436</nct_id>
  </id_info>
  <brief_title>Cytoreductive Surgery Combined With HIPEC and Chemotherapy for Gastric Cancer With Peritoneal Metastasis</brief_title>
  <official_title>Cytoreductive Surgery Combined With Hyperthermic Intraperitoneal Chemotherapy and Systemic Chemotherapy in Gastric Cancer With Regional Peritoneal Metastasis, a Multicenter and Single-arm Phase III Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nanfang Hospital, Southern Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Nanfang Hospital, Southern Medical University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates the survival benefit and safety of cytoreductive surgery(CRS) combined&#xD;
      with HIPEC and chemotherapy in gastric cancer with peritoneal metastasis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Peritoneal metastasis is one of the most frequent non-curable factors in advanced gastric&#xD;
      cancer with poor prognosis, the median survival time of patients is less than 1 year and even&#xD;
      worse in China. Recently, several new modalities have been developed and reported to improve&#xD;
      survival, including the new chemotherapeutic agents, molecular targeting agents and&#xD;
      hyperthermic intraperitoneal chemotherapy（HIPEC）.Still, the long-term outcomes based on&#xD;
      multicenter randomized clinical trials (RCTs) are awaited.&#xD;
&#xD;
      The surgical approach to metastatic lesions has been proved to play a very crucial role in&#xD;
      prolonging the survival of metastatic colorectal patients, which might be able to cure&#xD;
      patients with the operation aiming at R0 resection. For patients with metastatic gastric&#xD;
      cancer, surgical intervention of primary tumor and measurable metastatic lesion is&#xD;
      technically feasible, while the survival benefit is controversial. Even though the REGATTA&#xD;
      trial demonstrated that the removal of the primary tumor is not necessarily beneficial, the&#xD;
      role of operation aiming at R0 resection combined with new regimens like HIPEC and new&#xD;
      chemotherapeutic agents is still confusing and new categories of classification for&#xD;
      metastatic gastric cancer based on the treatment response is needed.&#xD;
&#xD;
      In order to evaluate the survival benefit and safety of cytoreductive surgery(CRS) and HIPEC&#xD;
      before beginning chemotherapy in gastric cancer with peritoneal metastasis, patients who&#xD;
      fulfill the inclusion and exclusion criteria will be recruited in this study and receive CRS,&#xD;
      HIPEC and chemotherapy. Chemotherapy regimen based on cisplatin and fluorouracil(CF) are&#xD;
      recommended. Patients are followed up for 2 years and the safety and survival outcome will be&#xD;
      analyzed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>January 2016</start_date>
  <completion_date type="Anticipated">June 2022</completion_date>
  <primary_completion_date type="Anticipated">June 2022</primary_completion_date>
  <phase>Phase 3</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>2-year Median survival time</measure>
    <time_frame>24 months</time_frame>
    <description>The time point when the cumulative survival rate is 50% according to the survival curve.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>2-year overall survival rate</measure>
    <time_frame>24 months</time_frame>
    <description>Overall survival rate calculated according to the survival curve.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival rate</measure>
    <time_frame>24 months</time_frame>
    <description>Progression free survival rate calculated according to the disease progression curve.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Morbidity and mortality</measure>
    <time_frame>30 days; 24 months</time_frame>
    <description>The early complication and mortality are defined as the event observed within 30 days after intervention, while the time frame for late complication is the period beyond 30 days after intervention to the end of month 24th. Complications are ranked from grade 0-5 according to CTCAE V4.0</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Quality of life(site-specific module for gastric cancer)</measure>
    <time_frame>Every 6 months to 2 years</time_frame>
    <description>Evaluated according to European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Stomach(EORTC QLQ-STO22)</description>
  </other_outcome>
  <other_outcome>
    <measure>Quality of life</measure>
    <time_frame>Every 6 months to 2 years</time_frame>
    <description>Evaluated according to European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Cancer (EORTC QLQ-C30)</description>
  </other_outcome>
  <other_outcome>
    <measure>circulating tumor cell（CTC） alteration</measure>
    <time_frame>Every 6 months to 2 years</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>circulating tumor DNA（ctDNA）alteration</measure>
    <time_frame>Every 3 months to 2 years</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Molecular biomarker alteration</measure>
    <time_frame>Every 6 months to 2 years</time_frame>
    <description>Molecular biomarker includes 14 genes（TP53, BAI1, THSD1, ARID2, KIAA2022, ERBB4, ZNF721, NT5E, PDE10A, CA1, NUMB, NBN, ZFYVE16 and NCAM1） according to the whole-exome sequencing results.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">220</enrollment>
  <condition>Stomach Neoplasm</condition>
  <arm_group>
    <arm_group_label>CRS + HIPEC + Systemic Chemotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cytoreductive surgery(CRS) followed by Hyperthermic Intraperitoneal Chemotherapy(HIPEC) and systemic chemotherapy will be performed for the treatment of patients assigned to this group.&#xD;
CF regimens or other first line regimens based on Fluoropyrimidine and Cisplatin according to the National Comprehensive Cancer Network（NCCN） Guidelines （Gastric Cancer，version 3.2016) are recommended.Regimens and dosing schedules are not limited in this trial.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Cytoreductive surgery</intervention_name>
    <description>Gastrectomy with D2 lymph node dissection and Metastasectomy for peritoneal metastatic sites only.&#xD;
A total, distal, or proximal gastrectomy and the type of reconstruction will be selected according to the surgeon's experience.&#xD;
Metastasectomy is limited to peritoneal metastatic sites only to render the patient no evidence of disease (NED) with at least 1cm negative margins when possible.</description>
    <arm_group_label>CRS + HIPEC + Systemic Chemotherapy</arm_group_label>
    <other_name>CRS , Cytoreduction Surgical Procedures</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Hyperthermic Intraperitoneal Chemotherapy</intervention_name>
    <description>Docetaxel 120 mg diluted in 5.0 L of saline is forced into the abdomen through the inflow catheter by a pump and pulled out through the drains as a heated intraperitoneal perfusion.A heat exchanger keeps the intraperitoneal fluid at 43±0.5℃ and duration limited to 70 minutes.24 hours after cytoreductive surgery no less than 2 cycles postoperative chemotherapy will be recommended.</description>
    <arm_group_label>CRS + HIPEC + Systemic Chemotherapy</arm_group_label>
    <other_name>HIPEC</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluoropyrimidine</intervention_name>
    <description>CF regimens or other first line regimens based on Fluoropyrimidine and Platinum according to the NCCN Guidelines（Gastric Cancer，version 3.2016) are recommended.Regimens and dosing schedules are not limited in this trial.</description>
    <arm_group_label>CRS + HIPEC + Systemic Chemotherapy</arm_group_label>
    <other_name>fluorouracil or capecitabine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>CF regimens or other first line regimens based on Fluoropyrimidine and Platinum according to the NCCN Guidelines（Gastric Cancer，version 3.2016) are recommended.Regimens and dosing schedules are not limited in this trial.</description>
    <arm_group_label>CRS + HIPEC + Systemic Chemotherapy</arm_group_label>
    <other_name>cis-diamine dichloroplatinum(CDDP)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age from over 18 to under 75 years&#xD;
&#xD;
          -  Histologically proven primary gastric adenocarcinoma confirmed pathologically by&#xD;
             endoscopic biopsy&#xD;
&#xD;
          -  Diagnosed with clinical T1-4N0-3M1（distant metastases confined to peritoneum,&#xD;
             P1）according to the American Joint Committee on Cancer(AJCC) Cancer Staging Manual&#xD;
             Seventh Edition by laparoscopic exploration&#xD;
&#xD;
          -  Localized peritoneal metastasis with peritoneal cancer index(PCI) less than 20&#xD;
&#xD;
          -  Resection of primary tumor and metastasis is anticipated to reach the CC0 status(no&#xD;
             residual tumor )&#xD;
&#xD;
          -  Performance status of 0 or 1 on Eastern Cooperative Oncology Group(ECOG) scale&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Adenocarcinoma of esophageal-gastric junction(AEG) that requires thoracotomy&#xD;
&#xD;
          -  Distant metastases not confined to peritoneum, including liver (H1), para-aortic&#xD;
             lymphnode (stations 16a1 and/or b2), lung, brain, bone and other organs&#xD;
&#xD;
          -  Histologically proven Human epidermal growth factor receptor 2(HER2)-neu&#xD;
             overexpressing adenocarcinoma&#xD;
&#xD;
          -  History of previous neoadjuvant chemotherapy , radiotherapy or clinical trial&#xD;
             treatment within 3 months&#xD;
&#xD;
          -  Contraindication for anesthesia, surgery, chemotherapeutic agents or HIPEC&#xD;
&#xD;
          -  Women of child-bearing potential who are pregnant or breastfeeding&#xD;
&#xD;
          -  History of prior/other malignancies within the 5 years prior to enrollment&#xD;
&#xD;
          -  Cerebrovascular accident occurred within 6 months (myocardial infarction, unstable&#xD;
             angina, cerebral infarction, or cerebral hemorrhage)&#xD;
&#xD;
          -  History of continuous systematic administration of corticosteroids within one month&#xD;
&#xD;
          -  Requirement of simultaneous surgery for other disease&#xD;
&#xD;
          -  Emergency surgery due to complication (bleeding, obstruction or perforation) caused by&#xD;
             gastric cancer&#xD;
&#xD;
          -  FEV1&lt;50% of predicted values&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>74 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Guoxin Li</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) Group; Nanfang Hospital, Southern Medical University, China</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Guoxin Li, M.D., Ph.D.</last_name>
    <phone>+86-138-0277-1450</phone>
    <email>gzliguoxin@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Hao Liu, M.D., Ph.D.</last_name>
    <phone>+86-138-2215-8578</phone>
    <email>liuhaofbi@163.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Peking University Cancer Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100-142</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xiangqian Su, M.D., Ph.D.</last_name>
      <phone>+86-138-0126-2916</phone>
    </contact>
    <investigator>
      <last_name>Xiangqian Su, M.D., Ph.D</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Fujian Provincial Hospital</name>
      <address>
        <city>Fuzhou</city>
        <state>Fujian</state>
        <zip>350-014</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Liangxiang Huang, M.D., Ph.D.</last_name>
      <phone>0086-138-5902-0211</phone>
    </contact>
    <investigator>
      <last_name>Liangxiang Huang, M.D., Ph.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sun Yat-sen University Cancer Center</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510-060</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zhiwei Zhou, M.D., Ph.D.</last_name>
      <phone>+86-139-0222-2859</phone>
      <email>zhouzhw@sysucc.org.cn</email>
    </contact>
    <investigator>
      <last_name>Zhiwei Zhou, M.D., Ph.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Guangdong General Hospital</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510-080</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yong Li, M.D., Ph.D.</last_name>
      <phone>+86-138-2217-7479</phone>
      <email>yuan821007@126.com</email>
    </contact>
    <investigator>
      <last_name>Yong Li, M.D., Ph.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Guangzhou Medical University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510-095</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Shuzhong Cui, M.D., Ph.D.</last_name>
      <phone>+86-138-0251-3800</phone>
      <email>cuishuzhong@126.com</email>
    </contact>
    <investigator>
      <last_name>cuishuzhong@126.com Cui, M.D., Ph.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Zhujiang Hospital of Southern Medical University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510-280</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jinlong Yu, M.D., Ph.D.</last_name>
      <phone>+86-131-8909-7861</phone>
      <email>yujinlong640506@163.com</email>
    </contact>
    <investigator>
      <last_name>Jinlong Yu, M.D., Ph.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Nanfang Hospital, Southern Medical University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510-515</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Guoxin Li, M.D., Ph.D.</last_name>
      <phone>+86-138-0277-1450</phone>
      <email>gzliguoxin@163.com</email>
    </contact>
    <contact_backup>
      <last_name>Hao Liu, M.D., Ph.D.</last_name>
      <phone>+86-138-2215-8578</phone>
      <email>liuhaofbi@163.com</email>
    </contact_backup>
    <investigator>
      <last_name>Guoxin Li, M.D., Ph.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Third Affiliated Hospital of Sun Yat-sen University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510-630</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hong-Bo Wei, M.D., Ph.D.</last_name>
      <phone>0086-18922102969</phone>
      <email>drweihb@126.com</email>
    </contact>
    <contact_backup>
      <last_name>Bo Wei, M.D.</last_name>
      <phone>0086-13527794069</phone>
      <email>sanpi2013@163.com</email>
    </contact_backup>
    <investigator>
      <last_name>Hong-Bo Wei, M.D., Ph.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Sixth Affiliated Hospital of Sun Yat-sen University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510-655</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Junsheng Peng, M.D., Ph.D.</last_name>
      <phone>+86-138-0296-3578</phone>
      <email>pengsir1010@126.com</email>
    </contact>
    <investigator>
      <last_name>Junsheng Peng, M.D., Ph.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Meizhou People's Hospital</name>
      <address>
        <city>Meizhou</city>
        <state>Guangdong</state>
        <zip>514-031</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zuguang Wu, M.D.</last_name>
      <phone>+86-135-0252-3063</phone>
      <email>wuzg1913@163.com</email>
    </contact>
    <investigator>
      <last_name>Zuguang Wu, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Zhongshan City People Hospital</name>
      <address>
        <city>Zhongshan</city>
        <state>Guangdong</state>
        <zip>528-403</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hong Chen, M.D., Ph.D.</last_name>
      <phone>+86-135-9084-3781</phone>
      <email>cenhong228@sohu.com</email>
    </contact>
    <investigator>
      <last_name>Hong Chen, M.D., Ph.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Zhongshan Hospital, Fudan University</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200-032</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yihong Sun, M.D., Ph.D.</last_name>
      <phone>+86-137-0173-5406</phone>
      <email>yihongsun@medmail.com.cn</email>
    </contact>
    <investigator>
      <last_name>Yihong Sun, M.D., Ph.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>West China Hospital, Sichuan University</name>
      <address>
        <city>Chengdu</city>
        <state>Sichuan</state>
        <zip>610-041</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jiankun Hu, M.D., Ph.D.</last_name>
      <phone>+86-189-8060-1504</phone>
      <email>hujkwch@126.com</email>
    </contact>
    <investigator>
      <last_name>Jiankun Hu, M.D.,Ph.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA; V325 Study Group. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006 Nov 1;24(31):4991-7. doi: 10.1200/JCO.2006.06.8429.</citation>
    <PMID>17075117</PMID>
  </reference>
  <reference>
    <citation>Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008 Mar;9(3):215-21. doi: 10.1016/S1470-2045(08)70035-4. Epub 2008 Feb 20.</citation>
    <PMID>18282805</PMID>
  </reference>
  <reference>
    <citation>Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Ruschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. doi: 10.1016/S0140-6736(10)61121-X. Epub 2010 Aug 19. Erratum In: Lancet. 2010 Oct 16;376(9749):1302.</citation>
    <PMID>20728210</PMID>
  </reference>
  <reference>
    <citation>Fujitani K, Yang HK, Mizusawa J, Kim YW, Terashima M, Han SU, Iwasaki Y, Hyung WJ, Takagane A, Park DJ, Yoshikawa T, Hahn S, Nakamura K, Park CH, Kurokawa Y, Bang YJ, Park BJ, Sasako M, Tsujinaka T; REGATTA study investigators. Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor (REGATTA): a phase 3, randomised controlled trial. Lancet Oncol. 2016 Mar;17(3):309-318. doi: 10.1016/S1470-2045(15)00553-7. Epub 2016 Jan 26.</citation>
    <PMID>26822397</PMID>
  </reference>
  <results_reference>
    <citation>Hu Y, Huang C, Sun Y, Su X, Cao H, Hu J, Xue Y, Suo J, Tao K, He X, Wei H, Ying M, Hu W, Du X, Chen P, Liu H, Zheng C, Liu F, Yu J, Li Z, Zhao G, Chen X, Wang K, Li P, Xing J, Li G. Morbidity and Mortality of Laparoscopic Versus Open D2 Distal Gastrectomy for Advanced Gastric Cancer: A Randomized Controlled Trial. J Clin Oncol. 2016 Apr 20;34(12):1350-7. doi: 10.1200/JCO.2015.63.7215. Epub 2016 Feb 22.</citation>
    <PMID>26903580</PMID>
  </results_reference>
  <results_reference>
    <citation>Geng X, Liu H, Lin T, Hu Y, Chen H, Zhao L, Mou T, Qi X, Yu J, Li G. Survival benefit of gastrectomy for gastric cancer with peritoneal carcinomatosis: a propensity score-matched analysis. Cancer Med. 2016 Oct;5(10):2781-2791. doi: 10.1002/cam4.877. Epub 2016 Sep 20.</citation>
    <PMID>27650694</PMID>
  </results_reference>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>January 9, 2017</study_first_submitted>
  <study_first_submitted_qc>January 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 18, 2017</study_first_posted>
  <last_update_submitted>September 11, 2019</last_update_submitted>
  <last_update_submitted_qc>September 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Nanfang Hospital, Southern Medical University</investigator_affiliation>
    <investigator_full_name>Guoxin Li</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Stomach Neoplasms</keyword>
  <keyword>Cytoreduction Surgical Procedures</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stomach Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Capecitabine</mesh_term>
  </intervention_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/NCT03023436
org study id: CLASS - 05
nct id: NCT03023436
lead sponsor: 
has dmc: Yes
This study evaluates the survival benefit and safety of cytoreductive surgery(CRS) combined
      with HIPEC and chemotherapy in gastric cancer with peritoneal metastasis.
Peritoneal metastasis is one of the most frequent non-curable factors in advanced gastric
      cancer with poor prognosis, the median survival time of patients is less than 1 year and even
      worse in China. Recently, several new modalities have been developed and reported to improve
      survival, including the new chemotherapeutic agents, molecular targeting agents and
      hyperthermic intraperitoneal chemotherapy（HIPEC）.Still, the long-term outcomes based on
      multicenter randomized clinical trials (RCTs) are awaited.

      The surgical approach to metastatic lesions has been proved to play a very crucial role in
      prolonging the survival of metastatic colorectal patients, which might be able to cure
      patients with the operation aiming at R0 resection. For patients with metastatic gastric
      cancer, surgical intervention of primary tumor and measurable metastatic lesion is
      technically feasible, while the survival benefit is controversial. Even though the REGATTA
      trial demonstrated that the removal of the primary tumor is not necessarily beneficial, the
      role of operation aiming at R0 resection combined with new regimens like HIPEC and new
      chemotherapeutic agents is still confusing and new categories of classification for
      metastatic gastric cancer based on the treatment response is needed.

      In order to evaluate the survival benefit and safety of cytoreductive surgery(CRS) and HIPEC
      before beginning chemotherapy in gastric cancer with peritoneal metastasis, patients who
      fulfill the inclusion and exclusion criteria will be recruited in this study and receive CRS,
      HIPEC and chemotherapy. Chemotherapy regimen based on cisplatin and fluorouracil(CF) are
      recommended. Patients are followed up for 2 years and the safety and survival outcome will be
      analyzed.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: 2-year Median survival time
time frame: 24 months
description: The time point when the cumulative survival rate is 50% according to the survival curve.
measure: 2-year overall survival rate
time frame: 24 months
description: Overall survival rate calculated according to the survival curve.
measure: Progression free survival rate
time frame: 24 months
description: Progression free survival rate calculated according to the disease progression curve.
measure: Morbidity and mortality
time frame: 30 days; 24 months
description: The early complication and mortality are defined as the event observed within 30 days after intervention, while the time frame for late complication is the period beyond 30 days after intervention to the end of month 24th. Complications are ranked from grade 0-5 according to CTCAE V4.0
measure: Quality of life(site-specific module for gastric cancer)
time frame: Every 6 months to 2 years
description: Evaluated according to European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Stomach(EORTC QLQ-STO22)
measure: Quality of life
time frame: Every 6 months to 2 years
description: Evaluated according to European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Cancer (EORTC QLQ-C30)
measure: circulating tumor cell（CTC） alteration
time frame: Every 6 months to 2 years
measure: circulating tumor DNA（ctDNA）alteration
time frame: Every 3 months to 2 years
measure: Molecular biomarker alteration
time frame: Every 6 months to 2 years
description: Molecular biomarker includes 14 genes（TP53, BAI1, THSD1, ARID2, KIAA2022, ERBB4, ZNF721, NT5E, PDE10A, CA1, NUMB, NBN, ZFYVE16 and NCAM1） according to the whole-exome sequencing results.
arm group label: CRS + HIPEC + Systemic Chemotherapy
arm group type: Experimental
description: Cytoreductive surgery(CRS) followed by Hyperthermic Intraperitoneal Chemotherapy(HIPEC) and systemic chemotherapy will be performed for the treatment of patients assigned to this group.
CF regimens or other first line regimens based on Fluoropyrimidine and Cisplatin according to the National Comprehensive Cancer Network（NCCN） Guidelines （Gastric Cancer，version 3.2016) are recommended.Regimens and dosing schedules are not limited in this trial.
intervention type: Procedure
intervention name: Cytoreductive surgery
description: Gastrectomy with D2 lymph node dissection and Metastasectomy for peritoneal metastatic sites only.
A total, distal, or proximal gastrectomy and the type of reconstruction will be selected according to the surgeon's experience.
Metastasectomy is limited to peritoneal metastatic sites only to render the patient no evidence of disease (NED) with at least 1cm negative margins when possible.
arm group label: CRS + HIPEC + Systemic Chemotherapy
other name: CRS , Cytoreduction Surgical Procedures
intervention type: Procedure
intervention name: Hyperthermic Intraperitoneal Chemotherapy
description: Docetaxel 120 mg diluted in 5.0 L of saline is forced into the abdomen through the inflow catheter by a pump and pulled out through the drains as a heated intraperitoneal perfusion.A heat exchanger keeps the intraperitoneal fluid at 43±0.5℃ and duration limited to 70 minutes.24 hours after cytoreductive surgery no less than 2 cycles postoperative chemotherapy will be recommended.
arm group label: CRS + HIPEC + Systemic Chemotherapy
other name: HIPEC
intervention type: Drug
intervention name: Fluoropyrimidine
description: CF regimens or other first line regimens based on Fluoropyrimidine and Platinum according to the NCCN Guidelines（Gastric Cancer，version 3.2016) are recommended.Regimens and dosing schedules are not limited in this trial.
arm group label: CRS + HIPEC + Systemic Chemotherapy
other name: fluorouracil or capecitabine
intervention type: Drug
intervention name: Cisplatin
description: CF regimens or other first line regimens based on Fluoropyrimidine and Platinum according to the NCCN Guidelines（Gastric Cancer，version 3.2016) are recommended.Regimens and dosing schedules are not limited in this trial.
arm group label: CRS + HIPEC + Systemic Chemotherapy
other name: cis-diamine dichloroplatinum(CDDP)
criteria: 
gender: All
minimum age: 19 Years
maximum age: 74 Years
healthy volunteers: No
last name: Guoxin Li
role: Principal Investigator
affiliation: Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) Group; Nanfang Hospital, Southern Medical University, China
last name: Guoxin Li, M.D., Ph.D.
phone: +86-138-0277-1450
email: gzliguoxin@163.com
last name: Hao Liu, M.D., Ph.D.
phone: +86-138-2215-8578
email: liuhaofbi@163.com
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: China
citation: Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA; V325 Study Group. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006 Nov 1;24(31):4991-7. doi: 10.1200/JCO.2006.06.8429.
PMID: 17075117
citation: Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008 Mar;9(3):215-21. doi: 10.1016/S1470-2045(08)70035-4. Epub 2008 Feb 20.
PMID: 18282805
citation: Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Ruschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. doi: 10.1016/S0140-6736(10)61121-X. Epub 2010 Aug 19. Erratum In: Lancet. 2010 Oct 16;376(9749):1302.
PMID: 20728210
citation: Fujitani K, Yang HK, Mizusawa J, Kim YW, Terashima M, Han SU, Iwasaki Y, Hyung WJ, Takagane A, Park DJ, Yoshikawa T, Hahn S, Nakamura K, Park CH, Kurokawa Y, Bang YJ, Park BJ, Sasako M, Tsujinaka T; REGATTA study investigators. Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor (REGATTA): a phase 3, randomised controlled trial. Lancet Oncol. 2016 Mar;17(3):309-318. doi: 10.1016/S1470-2045(15)00553-7. Epub 2016 Jan 26.
PMID: 26822397
citation: Hu Y, Huang C, Sun Y, Su X, Cao H, Hu J, Xue Y, Suo J, Tao K, He X, Wei H, Ying M, Hu W, Du X, Chen P, Liu H, Zheng C, Liu F, Yu J, Li Z, Zhao G, Chen X, Wang K, Li P, Xing J, Li G. Morbidity and Mortality of Laparoscopic Versus Open D2 Distal Gastrectomy for Advanced Gastric Cancer: A Randomized Controlled Trial. J Clin Oncol. 2016 Apr 20;34(12):1350-7. doi: 10.1200/JCO.2015.63.7215. Epub 2016 Feb 22.
PMID: 26903580
citation: Geng X, Liu H, Lin T, Hu Y, Chen H, Zhao L, Mou T, Qi X, Yu J, Li G. Survival benefit of gastrectomy for gastric cancer with peritoneal carcinomatosis: a propensity score-matched analysis. Cancer Med. 2016 Oct;5(10):2781-2791. doi: 10.1002/cam4.877. Epub 2016 Sep 20.
PMID: 27650694
responsible party type: Principal Investigator
investigator affiliation: Nanfang Hospital, Southern Medical University
investigator full name: Guoxin Li
investigator title: Principal Investigator
mesh term: Stomach Neoplasms
mesh term: Fluorouracil
mesh term: Capecitabine
sharing ipd: No