<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/NCT02980510</url>
  </required_header>
  <id_info>
    <org_study_id>UCGI 28 PANIRINOX</org_study_id>
    <secondary_id>2016-001490-33</secondary_id>
    <nct_id>NCT02980510</nct_id>
  </id_info>
  <brief_title>Comparison FOLFIRINOX Panitumumab vs mFOLFOX6 Panitumumab in RAS/B-RAF Wild-type Metastatic Colorectal Cancer Patients</brief_title>
  <acronym>PANIRINOX</acronym>
  <official_title>Phase II Randomized Study Comparing FOLFIRINOX + Panitumumab Versus mFOLFOX6 + Panitumumab in Metastatic Colorectal Cancer Patients Selected by RAS and B-RAF Status From Circulating DNA Analysis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>UNICANCER</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>UNICANCER</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>
      National trial, multicenter, randomized, phase II assessing FOLFIRINOX + Panitumumab versus&#xD;
      mFOLFOX6 + Panitumumab in metastatic colorectal cancer patients selected by RAS and B-RAF&#xD;
      status from circulating DNA analysis.&#xD;
&#xD;
      Evaluation of complete response rate on treatment combining FOLFIRINOX and panitumumab.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE: Evaluation of complete response rate on treatment combining FOLFIRINOX and&#xD;
      panitumumab&#xD;
&#xD;
      SECONDARY OBJECTIVE(S):&#xD;
&#xD;
        -  Overall Survival&#xD;
&#xD;
        -  Progression free survival&#xD;
&#xD;
        -  Secondary resection&#xD;
&#xD;
        -  Early tumor shrinkage (ETS)&#xD;
&#xD;
        -  Depth of response (DpR)&#xD;
&#xD;
        -  Safety profile (NCI-CTCAE v4.03 classification)&#xD;
&#xD;
        -  Diagnostic performance of ccfDNA analysis compared to the tumor-tissue analysis (current&#xD;
           gold standard)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 2016</start_date>
  <completion_date type="Anticipated">January 2025</completion_date>
  <primary_completion_date type="Anticipated">December 2024</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>
    <intervention_model_description>National trial, multicenter, randomized, phase II assessing FOLFIRINOX + Panitumumab versus mFOLFOX6 + Panitumumab in metastatic colorectal cancer patients selected by RAS and B-RAF status from circulating DNA analysis.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>The primary endpoint is the complete response rate where complete response is defined as complete disappearance of metastatic lesions after a maximum of 12 cycles of chemotherapy and tumor marker level normalization (CEA).</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Evaluation of complete response rate on treatment combining FOLFIRINOX and panitumumab.</measure>
    <time_frame>12 months after inclusion</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">219</enrollment>
  <condition>Metastatic Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>A=Experimental group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>FOLFIRINOX + Panitumumab oxaliplatin 85 mg/m² IV infusion over 2 hours immediately followed by folinic acid 400 mg/m² given as a 2-hour intravenous (IV) infusion with the addition, after 30 minutes of irinotecan 150 mg/m² given as a 90-minute intravenous infusion through a Y-connector immediately followed by fluorouracil 400 mg/m² IV bolus then 5-fluoruracil (5-FU) 2400 mg/m² over 46 hours continuous infusion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B=Control group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>mFOLFOX6 + Panitumumab mFOLFOX6 every 2 weeks: oxaliplatin 85 mg/m² IV infusion over 2 hours immediately followed by folinic acid 400 mg/m² IV infusion over 2 hours followed by fluorouracil 400 mg/m² IV bolus then 5-FU 2400 mg/m² over 46 hours continuous infusion.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Panitumumab, oxaliplatin, folinic acid, 5-fluoruracil</intervention_name>
    <arm_group_label>B=Control group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Panitumumab, oxaliplatin, folinic acid, 5-fluoruracil, irinotecan</intervention_name>
    <arm_group_label>A=Experimental group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age between 18 and 75 years&#xD;
&#xD;
          2. ECOG PS between 0 and 1&#xD;
&#xD;
          3. Histologically confirmed adenocarcinoma of the colon or rectum&#xD;
&#xD;
          4. Untreated synchronous or metachronous metastatic disease deemed unresectable with&#xD;
             curative intent&#xD;
&#xD;
          5. K-Ras (codons 12, 13, 59, 61, 117, 146), N-Ras (codons 12, 13, 59, 61) and B-Raf&#xD;
             (codon 600) wild-type tumor status according to plasma analysis of circulating cell&#xD;
             free DNA by Intplex technology&#xD;
&#xD;
          6. Measurable disease according to RECIST version 1.1&#xD;
&#xD;
          7. Adequate hematologic, hepatic and renal functions:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥2 x 109/L&#xD;
&#xD;
               -  Haemoglobin ≥9 g/dL&#xD;
&#xD;
               -  Platelets (PTL) ≥100 x 109/L&#xD;
&#xD;
               -  AST/ALT ≤5 x ULN&#xD;
&#xD;
               -  Alkaline phosphatase ≤2.5 x ULN&#xD;
&#xD;
               -  Bilirubin ≤1.5 x ULN&#xD;
&#xD;
               -  Creatinine clearance ≥50 mL/min (Cockcroft and Gault formula)&#xD;
&#xD;
          8. Life expectancy of at least 3 months&#xD;
&#xD;
          9. Adequate contraception if applicable&#xD;
&#xD;
         10. Patient affiliated to a social security regimen&#xD;
&#xD;
         11. Patient information and signed written consent form&#xD;
&#xD;
         12. Uracilemia &lt; 16 ng/ml&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of other malignancy within the previous 5 years (except for appropriately&#xD;
             treated in-situ cervix carcinoma and non-melanoma skin carcinoma)&#xD;
&#xD;
          2. Adjuvant treatment with oxaliplatin&#xD;
&#xD;
          3. Previous treatment for metastatic disease&#xD;
&#xD;
          4. Patients who received any chemo- and/or radiotherapy within 15 days from the date of&#xD;
             blood sampling for the RAS and BRAF test&#xD;
&#xD;
          5. Brain metastases&#xD;
&#xD;
          6. Patients with a history of severe or life-threatening hypersensitivity to the active&#xD;
             substances or to any of the excipients delivered in this study&#xD;
&#xD;
          7. Patient with history of pulmonary fibrosis or interstitial pneumonitis&#xD;
&#xD;
          8. Previous organ transplantation, HIV or other immunodeficiency syndromes&#xD;
&#xD;
          9. Concomitant medications/comorbidities that may prevent the patient from receiving&#xD;
             study treatment as uncontrolled intercurrent illness (for instance: active infection,&#xD;
             active inflammatory disorders, inflammatory bowel disease, intestinal obstruction,&#xD;
             symptomatic congestive heart failure, uncontrolled hypertension…)&#xD;
&#xD;
         10. Persistent peripheral neuropathy &gt;grade1 (NCI CT v4.03)&#xD;
&#xD;
         11. Ionic disorders as:&#xD;
&#xD;
               -  Kalemia ≤1 x LLN&#xD;
&#xD;
               -  Magnesemia &lt;0.5mmol/L&#xD;
&#xD;
               -  Calcemia &lt;2mmol/L&#xD;
&#xD;
         12. Patient with known dihydropyrimidine dehydrogenase deficiency&#xD;
&#xD;
         13. QT/QTc&gt;450msec for men and &gt;470msec for women&#xD;
&#xD;
         14. Patient with contraindication for trial drugs (investigators have to refer to SmPC&#xD;
             drugs, see Appendix 7)&#xD;
&#xD;
         15. Concomitant intake of St. John's wort&#xD;
&#xD;
         16. Other concomitant cancer&#xD;
&#xD;
         17. Participation in another therapeutic trial&#xD;
&#xD;
         18. Pregnant woman or lactating woman&#xD;
&#xD;
         19. Patients with psychological, familial, sociological or geographical condition&#xD;
             hampering compliance with the study protocol and follow-up schedule&#xD;
&#xD;
         20. Legal incapacity or limited legal capacity&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Thibault MAZARD</last_name>
    <role>Principal Investigator</role>
    <affiliation>ICM VAL D'AURELLE</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Institut Sainte Catherine</name>
      <address>
        <city>Avignon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Léon Berard</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu Saint Eloi</name>
      <address>
        <city>Montpellier</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ICM Val D'Aurelle</name>
      <address>
        <city>Montpellier</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut de Cancérologie de Lorraine</name>
      <address>
        <city>Nancy</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Carémeau - Institut de Cancérologie du Gard</name>
      <address>
        <city>Nimes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>November 30, 2016</study_first_submitted>
  <study_first_submitted_qc>December 1, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 2, 2016</study_first_posted>
  <last_update_submitted>August 30, 2023</last_update_submitted>
  <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 5, 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>Colorectal 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>Folic Acid</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
    <mesh_term>Irinotecan</mesh_term>
    <mesh_term>Panitumumab</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Levoleucovorin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.</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_time_frame>The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.</ipd_time_frame>
    <ipd_access_criteria>Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.</ipd_access_criteria>
  </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/NCT02980510
org study id: UCGI 28 PANIRINOX
secondary id: 2016-001490-33
nct id: NCT02980510
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
National trial, multicenter, randomized, phase II assessing FOLFIRINOX + Panitumumab versus
      mFOLFOX6 + Panitumumab in metastatic colorectal cancer patients selected by RAS and B-RAF
      status from circulating DNA analysis.

      Evaluation of complete response rate on treatment combining FOLFIRINOX and panitumumab.
PRIMARY OBJECTIVE: Evaluation of complete response rate on treatment combining FOLFIRINOX and
      panitumumab

      SECONDARY OBJECTIVE(S):

        -  Overall Survival

        -  Progression free survival

        -  Secondary resection

        -  Early tumor shrinkage (ETS)

        -  Depth of response (DpR)

        -  Safety profile (NCI-CTCAE v4.03 classification)

        -  Diagnostic performance of ccfDNA analysis compared to the tumor-tissue analysis (current
           gold standard)
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: National trial, multicenter, randomized, phase II assessing FOLFIRINOX + Panitumumab versus mFOLFOX6 + Panitumumab in metastatic colorectal cancer patients selected by RAS and B-RAF status from circulating DNA analysis.
primary purpose: Treatment
masking: None (Open Label)
masking description: The primary endpoint is the complete response rate where complete response is defined as complete disappearance of metastatic lesions after a maximum of 12 cycles of chemotherapy and tumor marker level normalization (CEA).
measure: Evaluation of complete response rate on treatment combining FOLFIRINOX and panitumumab.
time frame: 12 months after inclusion
arm group label: A=Experimental group
arm group type: Experimental
description: FOLFIRINOX + Panitumumab oxaliplatin 85 mg/m² IV infusion over 2 hours immediately followed by folinic acid 400 mg/m² given as a 2-hour intravenous (IV) infusion with the addition, after 30 minutes of irinotecan 150 mg/m² given as a 90-minute intravenous infusion through a Y-connector immediately followed by fluorouracil 400 mg/m² IV bolus then 5-fluoruracil (5-FU) 2400 mg/m² over 46 hours continuous infusion.
arm group label: B=Control group
arm group type: Active Comparator
description: mFOLFOX6 + Panitumumab mFOLFOX6 every 2 weeks: oxaliplatin 85 mg/m² IV infusion over 2 hours immediately followed by folinic acid 400 mg/m² IV infusion over 2 hours followed by fluorouracil 400 mg/m² IV bolus then 5-FU 2400 mg/m² over 46 hours continuous infusion.
intervention type: Drug
intervention name: Panitumumab, oxaliplatin, folinic acid, 5-fluoruracil
arm group label: B=Control group
intervention type: Drug
intervention name: Panitumumab, oxaliplatin, folinic acid, 5-fluoruracil, irinotecan
arm group label: A=Experimental group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Thibault MAZARD
role: Principal Investigator
affiliation: ICM VAL D'AURELLE
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Leucovorin
mesh term: Folic Acid
mesh term: Oxaliplatin
mesh term: Irinotecan
mesh term: Panitumumab
mesh term: Fluorouracil
mesh term: Levoleucovorin
sharing ipd: Yes
ipd description: Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.
ipd access criteria: Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.