<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/NCT02995850</url>
  </required_header>
  <id_info>
    <org_study_id>4-2016-0252</org_study_id>
    <nct_id>NCT02995850</nct_id>
  </id_info>
  <brief_title>A Phase Ib/II Study of Efficacy and Feasibility of Cytoreductive Surgery, Extensive Peritoneal Lavage, Hyperthermicintraperitoneal Chemotherapy and Post-operative Intraperitoneal Chemotherapy Combination in Gastric Cancer With Peritoneal Metastasis</brief_title>
  <official_title>A Phase Ib/II Study of Efficacy and Feasibility of Cytoreductive Surgery, Extensive Peritoneal Lavage, Hyperthermicintraperitoneal Chemotherapy and Post-operative Intraperitoneal Chemotherapy Combination in Gastric Cancer With Peritoneal Metastasis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yonsei University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Yonsei University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label, non-randomized, single-center, phase Ib/II study, evaluating efficacy&#xD;
      and feasibility of cytoreductive surgery(CRS), extensive peritoneal lavage, hyperthermic&#xD;
      intraperitoneal chemotherapy(HIPEC) and post-operative intraperitoneal chemotherapy&#xD;
      combination in gastric cancer with peritoneal metastasis&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Peritoneal metastases in gastric cancer are considered to indicate terminal disease due to&#xD;
      poor prognosis because systemic chemotherapy is unlikely to accumulate in peritoneal nodules&#xD;
      in cytotoxic concentrations. Cytoreductive surgery (CRS) along with hyperthermic&#xD;
      intraperitoneal chemotherapy (HIPEC) has been suggested to improve survival in select&#xD;
      patients with limited peritoneal spread, resulting in a median overall survival (OS) of 8 to&#xD;
      14 months. It remains unclear, however, which regimen is best and who have benefits from CRS&#xD;
      and HIPEC. Herein, we has conducting prospective phase Ib/II trial of CRC and HIPEC with&#xD;
      intraperitoneal paclitaxel and cisplatin, and oral S-1 in gastric cancer with peritoneal&#xD;
      metastasis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 22, 2017</start_date>
  <completion_date type="Actual">May 5, 2022</completion_date>
  <primary_completion_date type="Actual">April 19, 2022</primary_completion_date>
  <phase>Phase 1/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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Ib: Maximum tolerate dose</measure>
    <time_frame>3 months</time_frame>
    <description>Ib: To determine the MTD of orally administered S-1 + intraperitoneal paclitaxel +cisplatin in gastric cancer with peritoneal metastasis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>II: Safety</measure>
    <time_frame>3 months</time_frame>
    <description>II:To assess the safety and tolerability of CRS +HIPEC (Clavien-Dindo classification of surgical complication &amp; NCI-common terminology criteria for adverse events(CTC-AE) for chemotherapy]</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>OS (overall survival)</measure>
    <time_frame>12 months</time_frame>
    <description>the length of time from the patient signing the consent form until the patient is still alive</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS (Progression-free survival)</measure>
    <time_frame>12 months</time_frame>
    <description>the length of time from the patient signing the consent form until the patient shows disease progression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>RR (response rate)</measure>
    <time_frame>12 months</time_frame>
    <description>the proportion of complete response to partial response These will be estimated by the Kaplan-Meire method.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Gastric Cancer With Peritoneal Metastasis (PCI&lt;12)</condition>
  <arm_group>
    <arm_group_label>anti-cancer drug</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CRS+HIPEC</intervention_name>
    <description>Ib&#xD;
Dose-escalation of intraperitoneal paclitaxel will follow a modified 3 + 3 dose escalation procedure.&#xD;
II&#xD;
① CRS If PCI &lt;12, CRS will be performed by gastrectomy with D2-lymphadenectomy and resection of any involved adjacent structures.&#xD;
If PCI≥12, instead of CRS, 3 times of IP paclitaxel +cisplatin and oral S-1 chemotherapy every 3 weeks, and then PCI &lt;12, CRS will be done.&#xD;
② Extensiveintraperitoneal lavage Peritoneal lavage after CRS will be done with 10 L before HIPEC.&#xD;
③ HIPEC Following surgery HIPEC will be performed using CDDP (60 mg/m2) and PTX (P2RD mg/m2). IP chemotherapy will be performed.&#xD;
④ Post-operative intraperitoneal chemotherapy Postoperative chemotherapy will be done 8 cycles of IP paclitaxel+ cisplatin and oral S-1 after 4 weeks.</description>
    <arm_group_label>anti-cancer drug</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patient age of 19 years or older and age of 75 years or younger.&#xD;
&#xD;
          2. Histologically proven gastric or esophagogastric junction adenocarcinoma with&#xD;
             peritoneal metastasis under diagnostic laparoscopy.&#xD;
&#xD;
          3. Primary tumor measured as resectable in preoperative images.&#xD;
&#xD;
          4. Performance status based on ECOG : 0~1&#xD;
&#xD;
          5. No prior treatment (chemotherapy, radiotherapy, etc.)&#xD;
&#xD;
          6. Adequate hepatic, renal, and hematologic function&#xD;
&#xD;
               -  ANC≥1,500/uL,&#xD;
&#xD;
               -  hemoglobin≥9.0g/dL&#xD;
&#xD;
               -  platelet≥100,000/uL&#xD;
&#xD;
               -  total Bilirubin: ≤ 1.5 × upper normal limit&#xD;
&#xD;
               -  Creatinine&lt;1.5mg/dL&#xD;
&#xD;
               -  AST/ALT, ALP ≤ 2.5 x upper normal limit&#xD;
&#xD;
          7. Patients who can understand this study and sign the consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient who has distant metastasis or para-aortic lymph node metastasis or&#xD;
             retroperitoneal metastasis except peritoneal metastasis. (But the patient who has&#xD;
             ovarian metastasis with resectable status can be enrolled.)&#xD;
&#xD;
          2. Primary tumor cannot be resected because of direct invasion to other important organ.&#xD;
             (But, if the invaded organ can be resected together, such as spleen, gallbladder,&#xD;
             distal pancreas, and liver, the patient can be enrolled)&#xD;
&#xD;
          3. HER2 positive patient&#xD;
&#xD;
          4. Patient with active viral infection (for example, HIV, HBV, HCV, except stable status&#xD;
             of HBV infection)&#xD;
&#xD;
          5. Pregnant patient, or patient in breast-feeding, or who is planning pregnancy.&#xD;
&#xD;
          6. Patients in exclusion criteria of TS-1, cisplatin, paclitaxel&#xD;
&#xD;
               -  Patients with a history of severe hypersensitivity to these drugs&#xD;
&#xD;
               -  Patients with severe bone marrow depression&#xD;
&#xD;
               -  patients who has severe hepatic, renal disorder&#xD;
&#xD;
               -  patients who has hereditary problem or galactose intolerance, lapp lactase&#xD;
                  deficiency, or glucose-galactose malabsorption&#xD;
&#xD;
          7. Patients who has important medical problem or infection&#xD;
&#xD;
               -  Cerebrovascular accident(CVA) within 1 year&#xD;
&#xD;
               -  Heart attack within 6 months, uncontrolled hypertension, unstable angina,&#xD;
                  uncontrolled congestive heart failure(CHF), severe arrhythmia&#xD;
&#xD;
               -  Major operation or injury within 28 days&#xD;
&#xD;
               -  Severe and not recovered wound, ulcer, fracture&#xD;
&#xD;
               -  Uncontrolled bleeding disease&#xD;
&#xD;
               -  Recent active gastric infection&#xD;
&#xD;
          8. Patient with another primary cancer within last 5 years&#xD;
&#xD;
          9. Patient on medication which can interact with the drugs used in this study&#xD;
             (fluoropyrimidine-group antineoplastic agents, flucytosine, phenytoin, etc)&#xD;
&#xD;
         10. Patients with other systemic chemotherapy or radiotherapy&#xD;
&#xD;
         11. Patients with psychiatric or neurologic disorder so that he or she cannot understand&#xD;
             and sign the consent form.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Department of Surgery, Yonsei University College of Medicine</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>December 14, 2016</study_first_submitted>
  <study_first_submitted_qc>December 14, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 19, 2016</study_first_posted>
  <last_update_submitted>August 7, 2023</last_update_submitted>
  <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Stomach Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02995850
org study id: 4-2016-0252
nct id: NCT02995850
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is an open-label, non-randomized, single-center, phase Ib/II study, evaluating efficacy
      and feasibility of cytoreductive surgery(CRS), extensive peritoneal lavage, hyperthermic
      intraperitoneal chemotherapy(HIPEC) and post-operative intraperitoneal chemotherapy
      combination in gastric cancer with peritoneal metastasis
Peritoneal metastases in gastric cancer are considered to indicate terminal disease due to
      poor prognosis because systemic chemotherapy is unlikely to accumulate in peritoneal nodules
      in cytotoxic concentrations. Cytoreductive surgery (CRS) along with hyperthermic
      intraperitoneal chemotherapy (HIPEC) has been suggested to improve survival in select
      patients with limited peritoneal spread, resulting in a median overall survival (OS) of 8 to
      14 months. It remains unclear, however, which regimen is best and who have benefits from CRS
      and HIPEC. Herein, we has conducting prospective phase Ib/II trial of CRC and HIPEC with
      intraperitoneal paclitaxel and cisplatin, and oral S-1 in gastric cancer with peritoneal
      metastasis.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Ib: Maximum tolerate dose
time frame: 3 months
description: Ib: To determine the MTD of orally administered S-1 + intraperitoneal paclitaxel +cisplatin in gastric cancer with peritoneal metastasis.
measure: II: Safety
time frame: 3 months
description: II:To assess the safety and tolerability of CRS +HIPEC (Clavien-Dindo classification of surgical complication & NCI-common terminology criteria for adverse events(CTC-AE) for chemotherapy]
measure: OS (overall survival)
time frame: 12 months
description: the length of time from the patient signing the consent form until the patient is still alive
measure: PFS (Progression-free survival)
time frame: 12 months
description: the length of time from the patient signing the consent form until the patient shows disease progression
measure: RR (response rate)
time frame: 12 months
description: the proportion of complete response to partial response These will be estimated by the Kaplan-Meire method.
arm group label: anti-cancer drug
arm group type: Experimental
intervention type: Drug
intervention name: CRS+HIPEC
description: Ib
Dose-escalation of intraperitoneal paclitaxel will follow a modified 3 + 3 dose escalation procedure.
II
① CRS If PCI <12, CRS will be performed by gastrectomy with D2-lymphadenectomy and resection of any involved adjacent structures.
If PCI≥12, instead of CRS, 3 times of IP paclitaxel +cisplatin and oral S-1 chemotherapy every 3 weeks, and then PCI <12, CRS will be done.
② Extensiveintraperitoneal lavage Peritoneal lavage after CRS will be done with 10 L before HIPEC.
③ HIPEC Following surgery HIPEC will be performed using CDDP (60 mg/m2) and PTX (P2RD mg/m2). IP chemotherapy will be performed.
④ Post-operative intraperitoneal chemotherapy Postoperative chemotherapy will be done 8 cycles of IP paclitaxel+ cisplatin and oral S-1 after 4 weeks.
arm group label: anti-cancer drug
criteria: 
gender: All
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Neoplasm Metastasis
mesh term: Stomach Neoplasms
sharing ipd: Undecided