<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/NCT03795311</url>
  </required_header>
  <id_info>
    <org_study_id>FOLFIRINOX3</org_study_id>
    <nct_id>NCT03795311</nct_id>
  </id_info>
  <brief_title>Evaluation of the Efficacy and the Safety of FOLFIRINOX3 Bevacizumab Treatment in Patients With Colorectal Cancer (FOLFIRINOX 3)</brief_title>
  <acronym>FOLFIRINOX3</acronym>
  <official_title>Phase I / II Study Evaluating the Efficacy and Safety of FOLFIRINOX3 Bevacizumab Treatment in Patients With Colorectal Cancer Who Have Failed With Standard Chemotherapy Protocols (FOLFIRINOX 3)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Georges Francois Leclerc</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre Georges Francois Leclerc</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>
      In patients in progression after oxaliplatin and irinotecan, the study FOLFIRINOX 3 proposes&#xD;
      to evaluate the interest of modifying the standard pattern of administration of the molecule&#xD;
      of irinotecan in order to make it more efficient. In combination with other chemotherapy&#xD;
      drugs (5-fluorouracil, oxaliplatin, folinic acid and bevacizumab), irinotecan will be&#xD;
      administered at the beginning and end of each cycle of chemotherapy, whereas it is normally&#xD;
      administered at one time in the regimen. standard of treatment.&#xD;
&#xD;
      The hypothesis of this study is an increase in the objective response rate at 2 months of 10&#xD;
      to 30% with a scheme by FOLFIRINOX3 - bevacizumab compared to an optimal treatment to date by&#xD;
      FOLFIRINOX-bevacizumab.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary objective&#xD;
&#xD;
        -  Main objective of phase I: To evaluate the acute toxicity of treatment with FOLFIRINOX 3&#xD;
           - bevacizumab&#xD;
&#xD;
        -  Main objective of phase II: To evaluate the efficacy of treatment with FOLFIRINOX 3 -&#xD;
           bevacizumab in terms of objective response according to the RECIST criteria.&#xD;
&#xD;
      Secondary objectives&#xD;
&#xD;
        -  To evaluate the efficacy of treatment with FOLFIRINOX 3 - bevacizumab in terms of&#xD;
           objective response according to the criteria of CHOI, progression-free survival (PFS)&#xD;
           and overall survival (OS)&#xD;
&#xD;
        -  To evaluate the late toxicity of treatment with FOLFIRINOX 3 - bevacizumab&#xD;
&#xD;
        -  Evaluate the quality of life&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 7, 2018</start_date>
  <completion_date type="Anticipated">January 7, 2023</completion_date>
  <primary_completion_date type="Anticipated">January 7, 2023</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants with Acute toxicities as a Measure of treatment specific Safety and Tolerability</measure>
    <time_frame>each chemotherapy cycle (15 days) up to progression (6 months on average)</time_frame>
    <description>Acute toxicities will be assessed according to the NCI CTCAE v4.03</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">55</enrollment>
  <condition>Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>Administration of chemotherapy molecules</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The treatment period is divided into 15-day periods.&#xD;
Schema of the administration to the treatments which will proceed in the same way with each cycle:&#xD;
Bevacizumab (5 mg/kg; during 30 min) + Oxaliplatine (85 mg/m2, during 2 hours) + Acide folinique (400 mg/m2) or Levofolinate de calcium (200 mg/m2) AND Irinotecan (during 2 hours) + 5-fluorouracile (2400 mg/m2 ; 46 hours) + Irinotecan (1 hour)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FOLFIRINOX Bevacizumab</intervention_name>
    <description>In phase 1, the goal is to define the DLT (maximum tolerated dose). 3 levels of doses will be evaluated with a different dose of irinotecan in each level.&#xD;
Level -1: Bevacizumab + Oxaliplatine + Acide folinique + Irinotecan: 60mg / m2&#xD;
Level 0: Bevacizumab + Oxaliplatine + Acide folinique +Irinotecan: 70mg / m2&#xD;
Level 1: Bevacizumab + Oxaliplatine + Acide folinique +Irinotecan: 90mg / m2&#xD;
The inclusion of patients will start at level 0. Dose-limiting toxicities will be identified during the first 2 cycles.</description>
    <arm_group_label>Administration of chemotherapy molecules</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Men or women&#xD;
&#xD;
          2. Age ≥ 18 years&#xD;
&#xD;
          3. Performance status of 0 or 1 (WHO ECOG Index)&#xD;
&#xD;
          4. Patient with metastatic colon cancer&#xD;
&#xD;
          5. History of chemotherapy treatment including oxaliplatin, irinotecan, antiangiogenic&#xD;
             (bevacizumab or aflibercept) and anti-EGFR if indicated&#xD;
&#xD;
          6. Patient eligible for treatment with FOLFIRINOX bevacizumab&#xD;
&#xD;
          7. Tumor evaluation (thoraco-abdominopelvic CT scan) performed within 4 weeks before&#xD;
             inclusion with at least one measurable lesion according to RECIST criteria 1.1&#xD;
&#xD;
          8. Patient able and able to abide by the protocol throughout the study, including&#xD;
             treatment, visits, scheduled examinations and follow-up.&#xD;
&#xD;
          9. Biological values within the following limits:&#xD;
&#xD;
               -  Bilirubinemia ≤ 1.5 times the upper limit of normal (N)&#xD;
&#xD;
               -  ASAT and ALAT ≤ 5 N&#xD;
&#xD;
               -  Creatinine ≤ 1.5 N and creatinine clearance&gt; 60 mlmin&#xD;
&#xD;
               -  Neutrophils ≥ 1.5. 109 / L&#xD;
&#xD;
               -  Platelets ≥ 150. 109 / L&#xD;
&#xD;
               -  Hemoglobin ≥ 9 g / dL (patients can be included even if they have been&#xD;
                  transfused).&#xD;
&#xD;
               -  Albuminémie≥30g / L&#xD;
&#xD;
               -  Hepatitis B, C and HIV negative serologies&#xD;
&#xD;
         10. Information note given and signed informed consent&#xD;
&#xD;
         11. Patient affiliated to a social security scheme&#xD;
&#xD;
         12. Women must have effective contraception and must have a negative pregnancy test at the&#xD;
             time of entry into the study or must no longer be of childbearing age (ie,&#xD;
             postmenopausal, after 60 years and no menstruation for ≥1 year without any other&#xD;
             medical cause, OR history of hysterectomy, OR history of bilateral oophorectomy),&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Other cancer in the 5 years prior to entry into the trial or concomitant (except in&#xD;
             situ cancer of the cervix or basal cell carcinoma of the skin).&#xD;
&#xD;
          2. Presence of cerebral metastasis (s)&#xD;
&#xD;
          3. Prognosis estimated &lt;3 months&#xD;
&#xD;
          4. Presence of a contraindication to bevacizumab (major surgery in the previous 28 days,&#xD;
             risk of arterial thrombosis, risk of haemorrhage, deep vein thrombosis without&#xD;
             effective anticoagulant therapy or unbalanced anticoagulant therapy)&#xD;
&#xD;
          5. History of grade 4 toxicity to oxaliplatin, irinotecan, 5FU or bevacizumab&#xD;
&#xD;
          6. Persistence of neuropathy greater than a grade 1&#xD;
&#xD;
          7. Hypersensitivity to one of the compounds of the treatments&#xD;
&#xD;
          8. Participation in course or within 30 days prior to entry into the study to another&#xD;
             therapeutic trial with an experimental molecule.&#xD;
&#xD;
          9. Demonstration of a DPYD and / or UGT1A1 mutation&#xD;
&#xD;
         10. Unbalanced serious illness, underlying infection that may prevent the patient from&#xD;
             receiving treatment&#xD;
&#xD;
         11. Pregnancy (compulsory pregnancy test at baseline), breastfeeding or lack of effective&#xD;
             contraception for men and women of childbearing age&#xD;
&#xD;
         12. Psychiatric illness compromising understanding of information or completion of study&#xD;
&#xD;
         13. Patient under tutorship, curatorship or court of justice&#xD;
&#xD;
         14. Inability to sign informed consent or to undergo medical follow-up of the trial for&#xD;
             geographical, social or psychological reasons.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>François Ghiringhelli, PU PH</last_name>
    <phone>03 80 73 77 53</phone>
    <email>FGhiringhelli@cgfl.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Emilie REDERSTORFF</last_name>
    <phone>03 45 34 81 16</phone>
    <email>erederstorff@cgfl.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Centre Georges François Leclerc</name>
      <address>
        <city>Dijon</city>
        <zip>21000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>François Ghiringhelli, PU PH</last_name>
      <phone>03 80 73 77 53</phone>
      <email>FGhiringhelli@cgfl.fr</email>
    </contact>
    <contact_backup>
      <last_name>Emilie Rederstorff</last_name>
      <phone>03 45 34 81 16</phone>
      <email>erederstorgg@cgfl.fr</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>January 2, 2019</study_first_submitted>
  <study_first_submitted_qc>January 3, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 7, 2019</study_first_posted>
  <last_update_submitted>March 14, 2019</last_update_submitted>
  <last_update_submitted_qc>March 14, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 15, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>FOLFIRINOX3 Bevacizumab</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bevacizumab</mesh_term>
    <mesh_term>Folfirinox</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03795311
org study id: FOLFIRINOX3
nct id: NCT03795311
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
In patients in progression after oxaliplatin and irinotecan, the study FOLFIRINOX 3 proposes
      to evaluate the interest of modifying the standard pattern of administration of the molecule
      of irinotecan in order to make it more efficient. In combination with other chemotherapy
      drugs (5-fluorouracil, oxaliplatin, folinic acid and bevacizumab), irinotecan will be
      administered at the beginning and end of each cycle of chemotherapy, whereas it is normally
      administered at one time in the regimen. standard of treatment.

      The hypothesis of this study is an increase in the objective response rate at 2 months of 10
      to 30% with a scheme by FOLFIRINOX3 - bevacizumab compared to an optimal treatment to date by
      FOLFIRINOX-bevacizumab.
Primary objective

        -  Main objective of phase I: To evaluate the acute toxicity of treatment with FOLFIRINOX 3
           - bevacizumab

        -  Main objective of phase II: To evaluate the efficacy of treatment with FOLFIRINOX 3 -
           bevacizumab in terms of objective response according to the RECIST criteria.

      Secondary objectives

        -  To evaluate the efficacy of treatment with FOLFIRINOX 3 - bevacizumab in terms of
           objective response according to the criteria of CHOI, progression-free survival (PFS)
           and overall survival (OS)

        -  To evaluate the late toxicity of treatment with FOLFIRINOX 3 - bevacizumab

        -  Evaluate the quality of life
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants with Acute toxicities as a Measure of treatment specific Safety and Tolerability
time frame: each chemotherapy cycle (15 days) up to progression (6 months on average)
description: Acute toxicities will be assessed according to the NCI CTCAE v4.03
arm group label: Administration of chemotherapy molecules
arm group type: Experimental
description: The treatment period is divided into 15-day periods.
Schema of the administration to the treatments which will proceed in the same way with each cycle:
Bevacizumab (5 mg/kg; during 30 min) + Oxaliplatine (85 mg/m2, during 2 hours) + Acide folinique (400 mg/m2) or Levofolinate de calcium (200 mg/m2) AND Irinotecan (during 2 hours) + 5-fluorouracile (2400 mg/m2 ; 46 hours) + Irinotecan (1 hour)
intervention type: Drug
intervention name: FOLFIRINOX Bevacizumab
description: In phase 1, the goal is to define the DLT (maximum tolerated dose). 3 levels of doses will be evaluated with a different dose of irinotecan in each level.
Level -1: Bevacizumab + Oxaliplatine + Acide folinique + Irinotecan: 60mg / m2
Level 0: Bevacizumab + Oxaliplatine + Acide folinique +Irinotecan: 70mg / m2
Level 1: Bevacizumab + Oxaliplatine + Acide folinique +Irinotecan: 90mg / m2
The inclusion of patients will start at level 0. Dose-limiting toxicities will be identified during the first 2 cycles.
arm group label: Administration of chemotherapy molecules
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: François Ghiringhelli, PU PH
phone: 03 80 73 77 53
email: FGhiringhelli@cgfl.fr
last name: Emilie REDERSTORFF
phone: 03 45 34 81 16
email: erederstorff@cgfl.fr
facility: 
status: Recruiting
contact: 
contact backup: 
country: France
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Bevacizumab
mesh term: Folfirinox