<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/NCT04442984</url>
  </required_header>
  <id_info>
    <org_study_id>2020-01</org_study_id>
    <nct_id>NCT04442984</nct_id>
  </id_info>
  <brief_title>FOLFOX6 Versus mFOLFIRINOX as First Line Chemotherapy in Metastatic Gastric Cancer or Esophagogastric Junction Adenocarcinoma (Type II-III)</brief_title>
  <acronym>IRIGA</acronym>
  <official_title>FOLFOX6 Versus mFOLFIRINOX as First Line Chemotherapy in Metastatic Gastric or Esophagogastric Junction Adenocarcinoma (Type II-III): Open-label Randomized Phase 2/3 Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Blokhin's Russian Cancer Research Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Blokhin's Russian Cancer Research Center</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>
      Patients with metastatic adenocarcinoma of the stomach or the esophagogastric junction&#xD;
      (II-III type by Siewert) without previous therapy will be treated with one of two&#xD;
      chemotherapy combinations . One half of the patients gets 5-Fluorouracil (5-FU), Leucovorin,&#xD;
      Oxaliplatin (FOLFOX6), the others 5-Fluorouracil (5-FU), Leucovorin, Oxaliplatin and&#xD;
      Irinotecan (mFOLFIRINOX). Main objective of the study is progression free survival.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This parallel, randomized, open-label study 326 patients with metastatic ( adenocarcinoma of&#xD;
      the stomach or the esophagogastric junction without previous therapy will be included in this&#xD;
      study. After randomization patients receive 9 cycles FOLFOX6 or mFOLFIRINOX.&#xD;
&#xD;
      Stratification factors include ECOG, site of metastasis, age, pathological subtypes.&#xD;
&#xD;
      Efficacy will be evaluated every 3 cycles with RECIST. Toxicity will be assessed with WHO CTC&#xD;
      3.0 every 2 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 3, 2019</start_date>
  <completion_date type="Anticipated">November 3, 2024</completion_date>
  <primary_completion_date type="Anticipated">November 3, 2021</primary_completion_date>
  <phase>Phase 2</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>Progression-Free Survival</measure>
    <time_frame>36 months</time_frame>
    <description>PFS is defined as the time from the date of randomization to the date of the first documentation of progressive disease or date of death, whichever occurs first. For target lesions (TL), PD was defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD) of TLs, taking as a reference the smallest SLD recorded since the treatment started, or the appearance of one or more lesions. For non-target lesions (NTL), PD was defined as an unequivocal progression of existing NTLs. Participants were censored at the last date of tumor measurement, the last date in the study drug log, or the date of last follow-up.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>60 months</time_frame>
    <description>OS is defined as the time from the date of randomization to the date of death due to any cause. Participants were censored at the last date of tumor measurement, the last date in the study drug log or the date of last follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Confirmed Complete Response (CR) or Partial Response (PR) Determined by Response Evaluation Criteria in Solid Tumors (RECIST)</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment associated toxicities</measure>
    <time_frame>12 months</time_frame>
    <description>WHO CTC 3.0</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">326</enrollment>
  <condition>Gastric Carcinoma Stage IV</condition>
  <condition>Esophagogastric Junction Adenocarcinoma Stage IV</condition>
  <arm_group>
    <arm_group_label>FOLFOX6</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>5FU 400mg/m2 iv bolus d1, 5-FU 2400 mg/m² d1-2, Leucovorin 400 mg d1, Oxaliplatin 85 mg/m² d1, every two weeks (q2w) 9 cycles</description>
  </arm_group>
  <arm_group>
    <arm_group_label>mFOLFIRINOX</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Irinotecan 180mg/m2 d1, 5FU 250mg/m2 iv bolus d1, 5-FU 2200 mg/m² d1-2, Leucovorin 400 mg d1, Oxaliplatin 85 mg/m² d1, every two weeks (q2w) 9 cycles</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Irinotecan</intervention_name>
    <description>d1 Irinotecan 180mg/m² every two weeks</description>
    <arm_group_label>mFOLFIRINOX</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxaliplatin</intervention_name>
    <description>d1 Oxaliplatin 85 mg/m² every two weeks</description>
    <arm_group_label>FOLFOX6</arm_group_label>
    <arm_group_label>mFOLFIRINOX</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5-FU</intervention_name>
    <description>d1-2 5-FU 2200 mg/m² every two weeks</description>
    <arm_group_label>mFOLFIRINOX</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5-FU</intervention_name>
    <description>d1 5-FU 250 mg/m² every two weeks</description>
    <arm_group_label>mFOLFIRINOX</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Leucovorin</intervention_name>
    <description>d1 Leucovorin 400 mg every two weeks</description>
    <arm_group_label>FOLFOX6</arm_group_label>
    <arm_group_label>mFOLFIRINOX</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5-FU</intervention_name>
    <description>d1 5-FU 400 mg/m² every two weeks</description>
    <arm_group_label>FOLFOX6</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5-FU</intervention_name>
    <description>d1-2 5-FU 2400 mg/m² every two weeks</description>
    <arm_group_label>FOLFOX6</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. histologically confirmed locally advanced, recurrent or metastatic adenocarcinoma of&#xD;
             the esophagogastric junction (Siewert type II-III) or the stomach&#xD;
&#xD;
          2. no prior palliative chemotherapy or radiation therapy&#xD;
&#xD;
          3. Age 18-70 years (female and male)&#xD;
&#xD;
          4. Eastern Cooperative Oncology Group ≤ 2&#xD;
&#xD;
          5. Neutrophils&gt; 2.000/µl&#xD;
&#xD;
          6. Platelets &gt; 100.000/µl&#xD;
&#xD;
          7. Normal value of Serum Creatinin&#xD;
&#xD;
          8. Albumin level &gt; 29 г/л&#xD;
&#xD;
          9. Aspartate transaminase (AST) or alanine transaminase (ALT) less than 3 times the upper&#xD;
             limits of normal (ULN)&#xD;
&#xD;
         10. Total Bilirubin less than 1.5 times the ULN&#xD;
&#xD;
         11. Written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous palliative cytostatic chemotherapy&#xD;
&#xD;
          2. Cancer relapse&#xD;
&#xD;
          3. Complicated gastric cancer (perforation, bleeding, sub or decompensated stenosis,&#xD;
             dysphagia IV)&#xD;
&#xD;
          4. Diarrhea ≥ 2 according to the criteria of Common Terminology Criteria for Adverse&#xD;
             Events (CTCAE) version 4.1;&#xD;
&#xD;
          5. Hypersensitivity against 5- Fluorouracil, Leucovorin, Oxaliplatin, irinotecan&#xD;
&#xD;
          6. Existence of contraindications against 5- Fluorouracil, Leucovorin, Oxaliplatin,&#xD;
             Irinotecan or Docetaxel&#xD;
&#xD;
          7. Active coronary heart disease, Cardiomyopathy or cardiac insufficiency stage III-IV&#xD;
             according to New York Heart Association (NYHA)&#xD;
&#xD;
          8. Severe non-surgical accompanying disease or acute infection (uncontrolled arterial&#xD;
             hypertension, diabetes mellitus, stroke less than 6 months old, mental disorders,&#xD;
             other tumors and others)&#xD;
&#xD;
          9. Malignant secondary disease, dated back &lt; 5 years (exception: In-situ-carcinoma of the&#xD;
             cervix uteri, adequately treated skin basal cell carcinoma)&#xD;
&#xD;
         10. Peripheral polyneuropathy &gt; Grad II&#xD;
&#xD;
         11. Liver dysfunction (AST)/ALT&gt;3,0xULN, ALT&gt;3xULN, Bilirubin&gt;1,5xULN) Serum Creatinin&#xD;
             &gt;1,0xULN&#xD;
&#xD;
         12. Chronic inflammable gastro-intestinal disease&#xD;
&#xD;
         13. Inclusion in another clinical trial&#xD;
&#xD;
         14. Pregnancy or lactation&#xD;
&#xD;
         15. Hepatitis B or C in the active stage&#xD;
&#xD;
         16. Human immunodeficiency virus(HIV) infected&#xD;
&#xD;
         17. Serious concomitant somatic and mental illnesses / deviations or territorial causes&#xD;
             that may prevent the patient from participating in the protocol and observing the&#xD;
             protocol schedule&#xD;
&#xD;
         18. Foreigners or persons with limited legal status&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Tatiana Titova</last_name>
    <phone>+79152982811</phone>
    <email>tatiana.titovadoc@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Blokhin's Russian Cancer Research Center</name>
      <address>
        <city>Moscow</city>
        <zip>115478</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tatiana Titova</last_name>
      <phone>+79152982811</phone>
      <email>tatiana.titovadoc@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Artamonova Elena</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>June 17, 2020</study_first_submitted>
  <study_first_submitted_qc>June 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 23, 2020</study_first_posted>
  <last_update_submitted>April 11, 2021</last_update_submitted>
  <last_update_submitted_qc>April 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 13, 2021</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>Adenocarcinoma</mesh_term>
    <mesh_term>Stomach 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>Oxaliplatin</mesh_term>
    <mesh_term>Irinotecan</mesh_term>
    <mesh_term>Fluorouracil</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/NCT04442984
org study id: 2020-01
nct id: NCT04442984
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Patients with metastatic adenocarcinoma of the stomach or the esophagogastric junction
      (II-III type by Siewert) without previous therapy will be treated with one of two
      chemotherapy combinations . One half of the patients gets 5-Fluorouracil (5-FU), Leucovorin,
      Oxaliplatin (FOLFOX6), the others 5-Fluorouracil (5-FU), Leucovorin, Oxaliplatin and
      Irinotecan (mFOLFIRINOX). Main objective of the study is progression free survival.
This parallel, randomized, open-label study 326 patients with metastatic ( adenocarcinoma of
      the stomach or the esophagogastric junction without previous therapy will be included in this
      study. After randomization patients receive 9 cycles FOLFOX6 or mFOLFIRINOX.

      Stratification factors include ECOG, site of metastasis, age, pathological subtypes.

      Efficacy will be evaluated every 3 cycles with RECIST. Toxicity will be assessed with WHO CTC
      3.0 every 2 weeks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-Free Survival
time frame: 36 months
description: PFS is defined as the time from the date of randomization to the date of the first documentation of progressive disease or date of death, whichever occurs first. For target lesions (TL), PD was defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD) of TLs, taking as a reference the smallest SLD recorded since the treatment started, or the appearance of one or more lesions. For non-target lesions (NTL), PD was defined as an unequivocal progression of existing NTLs. Participants were censored at the last date of tumor measurement, the last date in the study drug log, or the date of last follow-up.
measure: Overall Survival (OS)
time frame: 60 months
description: OS is defined as the time from the date of randomization to the date of death due to any cause. Participants were censored at the last date of tumor measurement, the last date in the study drug log or the date of last follow-up
measure: Percentage of Participants With Confirmed Complete Response (CR) or Partial Response (PR) Determined by Response Evaluation Criteria in Solid Tumors (RECIST)
time frame: 12 months
measure: Duration of Response
time frame: 12 months
measure: Treatment associated toxicities
time frame: 12 months
description: WHO CTC 3.0
arm group label: FOLFOX6
arm group type: Active Comparator
description: 5FU 400mg/m2 iv bolus d1, 5-FU 2400 mg/m² d1-2, Leucovorin 400 mg d1, Oxaliplatin 85 mg/m² d1, every two weeks (q2w) 9 cycles
arm group label: mFOLFIRINOX
arm group type: Experimental
description: Irinotecan 180mg/m2 d1, 5FU 250mg/m2 iv bolus d1, 5-FU 2200 mg/m² d1-2, Leucovorin 400 mg d1, Oxaliplatin 85 mg/m² d1, every two weeks (q2w) 9 cycles
intervention type: Drug
intervention name: Irinotecan
description: d1 Irinotecan 180mg/m² every two weeks
arm group label: mFOLFIRINOX
intervention type: Drug
intervention name: Oxaliplatin
description: d1 Oxaliplatin 85 mg/m² every two weeks
arm group label: FOLFOX6
arm group label: mFOLFIRINOX
intervention type: Drug
intervention name: 5-FU
description: d1-2 5-FU 2200 mg/m² every two weeks
arm group label: mFOLFIRINOX
intervention type: Drug
intervention name: 5-FU
description: d1 5-FU 250 mg/m² every two weeks
arm group label: mFOLFIRINOX
intervention type: Drug
intervention name: Leucovorin
description: d1 Leucovorin 400 mg every two weeks
arm group label: FOLFOX6
arm group label: mFOLFIRINOX
intervention type: Drug
intervention name: 5-FU
description: d1 5-FU 400 mg/m² every two weeks
arm group label: FOLFOX6
intervention type: Drug
intervention name: 5-FU
description: d1-2 5-FU 2400 mg/m² every two weeks
arm group label: FOLFOX6
criteria: 
gender: All
gender based: Yes
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Tatiana Titova
phone: +79152982811
email: tatiana.titovadoc@gmail.com
facility: 
status: Recruiting
contact: 
investigator: 
country: Russian Federation
responsible party type: Sponsor
mesh term: Adenocarcinoma
mesh term: Stomach Neoplasms
mesh term: Leucovorin
mesh term: Oxaliplatin
mesh term: Irinotecan
mesh term: Fluorouracil
sharing ipd: No