xml: <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/NCT06028737</url>
    </required_header>
    <id_info>
      <org_study_id>241/4</org_study_id>
      <nct_id>NCT06028737</nct_id>
    </id_info>
    <brief_title>Total Neoadjuvant Chemotherapy in Locally Advanced Gastric and Gastroesophageal Junction Cancer</brief_title>
    <acronym>OCTASUR</acronym>
    <official_title>Total Neoadjuvant Chemotherapy With 5-fluoruracil, Leucovorin, Oxaliplatin and Docetaxel in Locally Advanced Gastric and Gastroesophageal Junction Cancer (OCTASUR): Randomized, Single Center, Open Label Trial, Phase 2/3</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Ukrainian Society of Clinical Oncology</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Ukrainian Society of Clinical Oncology</source>
    <oversight_info>
      <has_dmc>Yes</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>
        The main goal of this study is to investigate the histopathological regression rate in&#xD;
        patients with locally advanced gastric and gastroesophageal adenocarcinoma without previous&#xD;
        treatment who will be prospectively randomized into two groups to undergo one of two&#xD;
        chemotherapy regimens, followed by surgery:&#xD;
  &#xD;
          1. 8 cycles of Total Neoadjuvant ChemoTherapy (TNT) with 5-Fluorouracil (5-FU), Leucovorin,&#xD;
             Oxaliplatin and Docetaxel (FLOT) followed by surgery.&#xD;
  &#xD;
          2. 4 cycles of Neoadjuvant FLOT chemotherapy scheme preoperatively and 4 adjuvant FLOT&#xD;
             cycles postoperatively.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        758 participants with resectable locally advanced gastric and gastroesophageal (Siewert 2, 3)&#xD;
        adenocarcinoma (T3-4b, N1-3, M0) with no history of previous treatment will be included in&#xD;
        this study after reading and signing the informed consent. After the initial diagnostic&#xD;
        laparoscopy, patients will be randomized into two groups in a 1:1 ratio, with allocation to&#xD;
        one of the two study groups.&#xD;
  &#xD;
        Patients who will be randomized to the first (control) group will receive 8 cycles of&#xD;
        perioperative FLOT chemotherapy scheme: 4 cycles before surgical treatment and 4 cycles after&#xD;
        surgical intervention. Patients who will be randomized to the second (study) group will&#xD;
        receive 8 cycles of FLOT total neoadjuvant chemotherapy, followed by surgery.&#xD;
  &#xD;
        Primary endpoint of the study is pathomorphological tumor response rate. Secondary endpoints&#xD;
        are: perioperative morbidity and mortality (surgical and chemotherapeutic complications);&#xD;
        disease-free survival (DFS) and 1-, 3- and 5-years overall survival (OS); quality of life&#xD;
        during and after the treatment; correlation between the pathohistological response and&#xD;
        chemotherapy regimen.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 25, 2023</start_date>
    <completion_date type="Anticipated">December 2031</completion_date>
    <primary_completion_date type="Anticipated">December 2027</primary_completion_date>
    <phase>Phase 2/Phase 3</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>Histopathological tumor response rate (Becker regression criteria).</measure>
      <time_frame>14 days after surgery</time_frame>
      <description>To determine the pathohistological regression rate after 8 FLOT cycles in total neoadjuvant regimen compared to 4 FLOT cycles in neoadjuvant regimen.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Surgical complications rate.</measure>
      <time_frame>30 days after surgery.</time_frame>
      <description>To determine postoperative surgical complications rate and profile after the different chemotherapy regimens, according to Clavien-Dindo classification.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Chemotherapy toxicity rate and profile.</measure>
      <time_frame>At the end of each FLOT cycle (each cycle is 14 days), up to 14 days after the last cycle.</time_frame>
      <description>To determine chemotherapeutic toxicity profile, according to Common Terminology Criteria for Adverse Events (CTCEA 5.0).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Quality of patients' life, according to the European Organisation for Research and Treatment of Cancer core quality of life questionnaire (EORTC QLQ-30, QLQ-OG25).</measure>
      <time_frame>24 months.</time_frame>
      <description>To determine quality of life during the chemotherapy in both groups, after the surgery and 2 years follow-up after the completion of treatment, using EORTC QLQ-30, QLQ-OG25 questionnaires.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease-free survival.</measure>
      <time_frame>1 year after the last intervention.</time_frame>
      <description>To determine the efficacy of total neoadjuvant FLOT regimen compared to perioperative FLOT regimen.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Median overall survival.</measure>
      <time_frame>5 years follow-up after the last intervention.</time_frame>
      <description>To determine the efficacy of TNT FLOT regimen compared to perioperative FLOT regimen by assessment of overall survival.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Correlation between the pathohistological response and overall and disease-free survival.</measure>
      <time_frame>14 days after surgery.</time_frame>
      <description>To determine the correlation between the pathohistological response and overall and disease-free survival.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">758</enrollment>
    <condition>Gastric Cancer</condition>
    <condition>Stomach Cancer</condition>
    <condition>GastroEsophageal Cancer</condition>
    <condition>Gastric Adenocarcinoma</condition>
    <condition>Gastroesophageal Junction Adenocarcinoma</condition>
    <condition>Advanced Gastric Adenocarcinoma</condition>
    <condition>Gastric Neoplasm</condition>
    <condition>Stomach Neoplasm</condition>
    <condition>Gastrointestinal Cancer</condition>
    <condition>Advanced Gastroesophageal Junction Adenocarcinoma</condition>
    <condition>Advanced Gastric Carcinoma</condition>
    <arm_group>
      <arm_group_label>Perioperative 4+4 FLOT cycles</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>4 cycles of neoadjuvant FLOT chemotherapy scheme, followed by surgery and 4 cycles of adjuvant FLOT chemotherapy scheme.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Total Neoadjuvant ChemoTherapy (TNT) 8 FLOT cycles</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>8 cycles of total neoadjuvant FLOT chemotherapy scheme, followed by surgery.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Docetaxel</intervention_name>
      <description>50mg/m2, d1, i.v., every 2 weeks</description>
      <arm_group_label>Perioperative 4+4 FLOT cycles</arm_group_label>
      <arm_group_label>Total Neoadjuvant ChemoTherapy (TNT) 8 FLOT cycles</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Oxaliplatin</intervention_name>
      <description>85 mg/m², d1, i.v., every 2 weeks</description>
      <arm_group_label>Perioperative 4+4 FLOT cycles</arm_group_label>
      <arm_group_label>Total Neoadjuvant ChemoTherapy (TNT) 8 FLOT cycles</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Leucovorin</intervention_name>
      <description>200 mg/m², d1, i.v., every 2 weeks</description>
      <arm_group_label>Perioperative 4+4 FLOT cycles</arm_group_label>
      <arm_group_label>Total Neoadjuvant ChemoTherapy (TNT) 8 FLOT cycles</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Fluorouracil</intervention_name>
      <description>2600 mg/m²d1 i.v. every 2 weeks</description>
      <arm_group_label>Perioperative 4+4 FLOT cycles</arm_group_label>
      <arm_group_label>Total Neoadjuvant ChemoTherapy (TNT) 8 FLOT cycles</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Tumor spread: сT3, сT4a, сТ4b (except of invasion of the common hepatic artery, celiac&#xD;
               trunk, proximal part of the splenic artery, aorta, head of the pancreas); сN1, сN2,&#xD;
               сN3; сM0;&#xD;
  &#xD;
            -  Performance status by Eastern Cooperative Oncology Group (ECOG): 0 - 1;&#xD;
  &#xD;
            -  Histological type of tumor: adenocarcinoma;&#xD;
  &#xD;
            -  Differentiation grade: G0 - G4;&#xD;
  &#xD;
            -  Tumor localization: cardio-esophageal junction (Siewert 2, 3), cardiac part of the&#xD;
               stomach, body of the stomach, antral part of the stomach, pyloric part of the stomach;&#xD;
  &#xD;
            -  Tumor extension: esophagus, diaphragm, liver, body and tail of the pancreas, anterior&#xD;
               abdominal wall, small and large intestine, distal part of the splenic artery, spleen;&#xD;
  &#xD;
            -  No history of cancer in the past 5 years;&#xD;
  &#xD;
            -  Absence of previous chemotherapeutic, surgical or radiation treatment for oncological&#xD;
               disease;&#xD;
  &#xD;
            -  No concomitant severe comorbidity;&#xD;
  &#xD;
            -  Patient willing to participate.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  M1 (distant metastases);&#xD;
  &#xD;
            -  ECOG 2 - 4;&#xD;
  &#xD;
            -  Age over 80 and under 18;&#xD;
  &#xD;
            -  Concomitant severe comorbidity;&#xD;
  &#xD;
            -  Refusal of the patient to participate in the study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>80 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Mykyta Pepenin, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>National Cancer Institute (NCI)</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Mykyta Pepenin, MD</last_name>
      <phone>+380959448858</phone>
      <email>pepenin95@gmail.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Oleksii Dobrzhanksiy, MD</last_name>
      <phone>+380638760185</phone>
      <email>alekseydobrzhanskiy@gmail.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>National Cancer Institute</name>
        <address>
          <city>Kyiv</city>
          <zip>03022</zip>
          <country>Ukraine</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Mykyta Pepenin, MD</last_name>
        <phone>+380959448858</phone>
        <email>pepenin95@gmail.com</email>
      </contact>
      <contact_backup>
        <last_name>Andrii Horodetskiy</last_name>
        <phone>+380990864410</phone>
        <email>gorodeckij03@gmail.com</email>
      </contact_backup>
      <investigator>
        <last_name>Mykyta Pepenin, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Ukraine</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 26, 2023</study_first_submitted>
    <study_first_submitted_qc>August 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 8, 2023</study_first_posted>
    <last_update_submitted>August 31, 2023</last_update_submitted>
    <last_update_submitted_qc>August 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Total neoadjuvant chemotherapy</keyword>
    <keyword>FLOT</keyword>
    <keyword>Fluoruracil</keyword>
    <keyword>Gastrectomy</keyword>
    <keyword>Perioperative chemotherapy</keyword>
    <keyword>Docetaxel</keyword>
    <keyword>Leucovorin</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Neoplasms</mesh_term>
      <mesh_term>Adenocarcinoma</mesh_term>
      <mesh_term>Stomach Neoplasms</mesh_term>
      <mesh_term>Esophageal Neoplasms</mesh_term>
      <mesh_term>Gastrointestinal Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Leucovorin</mesh_term>
      <mesh_term>Docetaxel</mesh_term>
      <mesh_term>Fluorouracil</mesh_term>
      <mesh_term>Oxaliplatin</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>After the initial publication every participant will receive all the data to provide further data exploration.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
      <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
      <ipd_time_frame>Data will be available after initial paper is published.</ipd_time_frame>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06028737
  org study id: 241/4
  nct id: NCT06028737
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  The main goal of this study is to investigate the histopathological regression rate in
        patients with locally advanced gastric and gastroesophageal adenocarcinoma without previous
        treatment who will be prospectively randomized into two groups to undergo one of two
        chemotherapy regimens, followed by surgery:
  
          1. 8 cycles of Total Neoadjuvant ChemoTherapy (TNT) with 5-Fluorouracil (5-FU), Leucovorin,
             Oxaliplatin and Docetaxel (FLOT) followed by surgery.
  
          2. 4 cycles of Neoadjuvant FLOT chemotherapy scheme preoperatively and 4 adjuvant FLOT
             cycles postoperatively.
  758 participants with resectable locally advanced gastric and gastroesophageal (Siewert 2, 3)
        adenocarcinoma (T3-4b, N1-3, M0) with no history of previous treatment will be included in
        this study after reading and signing the informed consent. After the initial diagnostic
        laparoscopy, patients will be randomized into two groups in a 1:1 ratio, with allocation to
        one of the two study groups.
  
        Patients who will be randomized to the first (control) group will receive 8 cycles of
        perioperative FLOT chemotherapy scheme: 4 cycles before surgical treatment and 4 cycles after
        surgical intervention. Patients who will be randomized to the second (study) group will
        receive 8 cycles of FLOT total neoadjuvant chemotherapy, followed by surgery.
  
        Primary endpoint of the study is pathomorphological tumor response rate. Secondary endpoints
        are: perioperative morbidity and mortality (surgical and chemotherapeutic complications);
        disease-free survival (DFS) and 1-, 3- and 5-years overall survival (OS); quality of life
        during and after the treatment; correlation between the pathohistological response and
        chemotherapy regimen.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Histopathological tumor response rate (Becker regression criteria).
  time frame: 14 days after surgery
  description: To determine the pathohistological regression rate after 8 FLOT cycles in total neoadjuvant regimen compared to 4 FLOT cycles in neoadjuvant regimen.
  measure: Surgical complications rate.
  time frame: 30 days after surgery.
  description: To determine postoperative surgical complications rate and profile after the different chemotherapy regimens, according to Clavien-Dindo classification.
  measure: Chemotherapy toxicity rate and profile.
  time frame: At the end of each FLOT cycle (each cycle is 14 days), up to 14 days after the last cycle.
  description: To determine chemotherapeutic toxicity profile, according to Common Terminology Criteria for Adverse Events (CTCEA 5.0).
  measure: Quality of patients' life, according to the European Organisation for Research and Treatment of Cancer core quality of life questionnaire (EORTC QLQ-30, QLQ-OG25).
  time frame: 24 months.
  description: To determine quality of life during the chemotherapy in both groups, after the surgery and 2 years follow-up after the completion of treatment, using EORTC QLQ-30, QLQ-OG25 questionnaires.
  measure: Disease-free survival.
  time frame: 1 year after the last intervention.
  description: To determine the efficacy of total neoadjuvant FLOT regimen compared to perioperative FLOT regimen.
  measure: Median overall survival.
  time frame: 5 years follow-up after the last intervention.
  description: To determine the efficacy of TNT FLOT regimen compared to perioperative FLOT regimen by assessment of overall survival.
  measure: Correlation between the pathohistological response and overall and disease-free survival.
  time frame: 14 days after surgery.
  description: To determine the correlation between the pathohistological response and overall and disease-free survival.
  arm group label: Perioperative 4+4 FLOT cycles
  arm group type: Active Comparator
  description: 4 cycles of neoadjuvant FLOT chemotherapy scheme, followed by surgery and 4 cycles of adjuvant FLOT chemotherapy scheme.
  arm group label: Total Neoadjuvant ChemoTherapy (TNT) 8 FLOT cycles
  arm group type: Experimental
  description: 8 cycles of total neoadjuvant FLOT chemotherapy scheme, followed by surgery.
  intervention type: Drug
  intervention name: Docetaxel
  description: 50mg/m2, d1, i.v., every 2 weeks
  arm group label: Perioperative 4+4 FLOT cycles
  arm group label: Total Neoadjuvant ChemoTherapy (TNT) 8 FLOT cycles
  intervention type: Drug
  intervention name: Oxaliplatin
  description: 85 mg/m², d1, i.v., every 2 weeks
  arm group label: Perioperative 4+4 FLOT cycles
  arm group label: Total Neoadjuvant ChemoTherapy (TNT) 8 FLOT cycles
  intervention type: Drug
  intervention name: Leucovorin
  description: 200 mg/m², d1, i.v., every 2 weeks
  arm group label: Perioperative 4+4 FLOT cycles
  arm group label: Total Neoadjuvant ChemoTherapy (TNT) 8 FLOT cycles
  intervention type: Drug
  intervention name: Fluorouracil
  description: 2600 mg/m²d1 i.v. every 2 weeks
  arm group label: Perioperative 4+4 FLOT cycles
  arm group label: Total Neoadjuvant ChemoTherapy (TNT) 8 FLOT cycles
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 80 Years
  healthy volunteers: No
  last name: Mykyta Pepenin, MD
  role: Principal Investigator
  affiliation: National Cancer Institute (NCI)
  last name: Mykyta Pepenin, MD
  phone: +380959448858
  email: pepenin95@gmail.com
  last name: Oleksii Dobrzhanksiy, MD
  phone: +380638760185
  email: alekseydobrzhanskiy@gmail.com
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  investigator: 
  country: Ukraine
  responsible party type: Sponsor
  mesh term: Neoplasms
  mesh term: Adenocarcinoma
  mesh term: Stomach Neoplasms
  mesh term: Esophageal Neoplasms
  mesh term: Gastrointestinal Neoplasms
  mesh term: Leucovorin
  mesh term: Docetaxel
  mesh term: Fluorouracil
  mesh term: Oxaliplatin
  sharing ipd: Yes
  ipd description: After the initial publication every participant will receive all the data to provide further data exploration.
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd info type: Informed Consent Form (ICF)
  ipd info type: Clinical Study Report (CSR)
  ipd time frame: Data will be available after initial paper is published.