<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/NCT03231722</url>
  </required_header>
  <id_info>
    <org_study_id>TRIPLETE</org_study_id>
    <nct_id>NCT03231722</nct_id>
  </id_info>
  <brief_title>First Line mFOLFOXIRI + PANITUMUMAB vs mFOLFOX + PANITUMUMAB IN RAS AND BRAF WT METASTATIC COLORECTAL CANCER PATIENTS</brief_title>
  <acronym>TRIPLETE</acronym>
  <official_title>The TRIPLETE Study RANDOMIZED PHASE III STUDY OF TRIPLET mFOLFOXIRI PLUS PANITUMUMAB Versus mFOLFOX6 PLUS PANITUMUMAB AS INITIAL THERAPY FOR UNRESECTABLE RAS AND BRAF WILDTYPE METASTATIC COLORECTAL CANCER PATIENTS</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gruppo Oncologico del Nord-Ovest</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Gruppo Oncologico del Nord-Ovest</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      -  The association of FOLFOX (5-fluoruracil, folinic acid, and oxaliplatin) and pan is a&#xD;
           standard option for the first-line treatment of unresectable RAS and BRAF wt mCRC&#xD;
           patients.&#xD;
&#xD;
        -  The phase III TRIBE trial recently demonstrated that FOLFOXIRI (5-fluoruracil, folinic&#xD;
           acid, oxaliplatin and irinotecan) plus bev significantly prolongs PFS and OS and&#xD;
           increases RECIST response rate, ETS and DoR, as compared to FOLFIRI (5-fluoruracil&#xD;
           folinic acid, and irinotecan) plus bev. The advantage provided by the intensification of&#xD;
           the upfront chemotherapy backbone is independent of RAS and BRAF mutational status.&#xD;
&#xD;
        -  Some phase II trials recently assessed the safety and activity of the combination of&#xD;
           three-drugs chemotherapy regimens with an anti-EGFR monoclonal antibody. Promising&#xD;
           activity results in terms of RECIST response rate and R0 resection rate have been&#xD;
           achieved, with some safety concerns with special regards to gastrointestinal toxicity.&#xD;
&#xD;
        -  In the phase II randomized MACBETH study the combination of a modified schedule of&#xD;
           FOLFOXIRI with cetuximab determined remarkable activity results, with an acceptable and&#xD;
           manageable safety profile.&#xD;
&#xD;
        -  The optimal duration of the upfront treatment with chemotherapy plus anti-EGFRs is not&#xD;
           established. The phase II MACRO-2 trial suggested that interrupting FOLFOX after 4&#xD;
           months while continuing cet alone as maintenance, is a reasonable option.&#xD;
&#xD;
        -  Activity parameters (RECIST response rate, ETS, DoR) are clinically relevant endpoints,&#xD;
           associated with longer survival, in particular with anti-EGFR moAb-based treatment.&#xD;
&#xD;
      On the basis of these considerations, we designed the present phase III randomized trial of&#xD;
      first-line mFOLFOXIRI plus pan versus mFOLFOX6 plus pan in RAS and BRAF wt unresectable mCRC&#xD;
      patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 13, 2017</start_date>
  <completion_date type="Actual">June 24, 2022</completion_date>
  <primary_completion_date type="Actual">June 15, 2022</primary_completion_date>
  <phase>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>
    <masking_description>open label</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Overall response rate</measure>
    <time_frame>12 months</time_frame>
    <description>the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Toxicity Rate</measure>
    <time_frame>24 months</time_frame>
    <description>the percentage of patients, relative to the total of enrolled subjects, experiencing any adverse event, according to National Cancer Institute Common Toxicity Criteria (version 4.0)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity Rate</measure>
    <time_frame>24 months</time_frame>
    <description>the percentage of patients, relative to the total of enrolled subjects, experiencing a specific adverse event of grade 3/4, according to National Cancer Institute Common Toxicity Criteria (version 4.0)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>24 months</time_frame>
    <description>the time from randomization to the first documentation of objective disease progression or death due to any cause, whichever occurs first. Documentation of disease progressive disease is defined as per RECIST 1.1 criteria based on investigator assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>48 months</time_frame>
    <description>the time from randomization to the date of death due to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Centrally assessed Overall response rate</measure>
    <time_frame>12 months</time_frame>
    <description>the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria based on central re-evaluation of CT scan images.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Early Tumour Shrinkage Rate</measure>
    <time_frame>up to 2 months from randomization</time_frame>
    <description>the percentage of patients, relative to the total of the enrolled subjects, achieving a ≥20% decrease in the sum of diameters of RECIST target lesions at week 8 compared to baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Deepness of Response</measure>
    <time_frame>12 months</time_frame>
    <description>the relative change in the sum of longest diameters of RECIST target lesions at the nadir, in the absence of new lesions or progression of non-target lesions, when compared with baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>R0 Resection Rate</measure>
    <time_frame>12 months</time_frame>
    <description>the percentage of patients, relative to the total of enrolled subjects, undergoing secondary R0 resection of metastases</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">435</enrollment>
  <condition>Metastatic Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>mFOLFOX6 + Panitumab</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Panitumumab 6 mg/kg iv over 60 minutes, day 1 (if the first infusion is tolerated, then subsequent infusions may be administered over 30 to 60 minutes) followed by&#xD;
Oxaliplatin 85 mg/sqm iv over 2 hours, day 1 in two-way with&#xD;
L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by&#xD;
5-fluorouracil 400 mg/sqm iv bolus, day 1 followed by&#xD;
5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. If no progression occurs, patients will receive maintenance with 5FU/LV plus pan at the same dose used at the last cycle of the induction treatment. 5FU/LV plus pan will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal. The prosecution of pan until disease progression is recommended also if 5-FU is interrupted because of adverse events, patient's refusal or investigator's choice.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>mFOLFOXIRI + Panitumumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Panitumumab 6 mg/kg iv over 60 minutes, day 1 (if the first infusion is tolerated, then subsequent infusions may be administered over 30 to 60 minutes) followed by&#xD;
Irinotecan 150 mg/sqm iv over 60 minutes day 1, followed by&#xD;
Oxaliplatin 85 mg/sqm iv over 2 hours day 1, in two-way with&#xD;
L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by&#xD;
5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. If no progression occurs, patients will receive maintenance with 5FU/LV plus pan at the same dose used at the last cycle of the induction treatment. 5FU/LV plus pan will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal. The prosecution of pan until disease progression is recommended also if 5-FU is interrupted because of adverse events, patient's refusal or investigator's choice.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Panitumumab</intervention_name>
    <description>6 mg/kg iv over 60 minutes, day 1</description>
    <arm_group_label>mFOLFOX6 + Panitumab</arm_group_label>
    <arm_group_label>mFOLFOXIRI + Panitumumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Irinotecan</intervention_name>
    <description>150 mg/sqm iv over 60 minutes day 1</description>
    <arm_group_label>mFOLFOX6 + Panitumab</arm_group_label>
    <arm_group_label>mFOLFOXIRI + Panitumumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxaliplatin</intervention_name>
    <description>85 mg/sqm iv over 2 hours day 1</description>
    <arm_group_label>mFOLFOXIRI + Panitumumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>l-leucovorin</intervention_name>
    <description>200 mg/sqm iv over 2 hours</description>
    <arm_group_label>mFOLFOX6 + Panitumab</arm_group_label>
    <arm_group_label>mFOLFOXIRI + Panitumumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5-fluorouracil</intervention_name>
    <description>400 mg/sqm iv bolus, day 1 followed by 2400 mg/sqm 48 h-continuous infusion, starting on day 1;</description>
    <arm_group_label>mFOLFOX6 + Panitumab</arm_group_label>
    <arm_group_label>mFOLFOXIRI + Panitumumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent to study procedures and to molecular analyses.&#xD;
&#xD;
          -  Histologically proven diagnosis of colorectal cancer.&#xD;
&#xD;
          -  Initially unresectable metastatic colorectal cancer not previously treated with&#xD;
             chemotherapy for metastatic disease.&#xD;
&#xD;
          -  At least one measurable lesion according to RECIST 1.1.&#xD;
&#xD;
          -  Availability of a tumour tissue sample (primary tumour and/or metastatic sites).&#xD;
&#xD;
          -  Male or female of 18-75 years of age&#xD;
&#xD;
          -  ECOG PS ≤2 for patients aged ≤70 years; ECOG PS 0 for patients aged 71 to 75 years.&#xD;
&#xD;
          -  Life expectancy of at least 12 weeks&#xD;
&#xD;
          -  Previous adjuvant chemotherapy allowed only if with fluoropyrimidine monotherapy and&#xD;
             more than 6 months elapsed between the end of adjuvant and first relapse.&#xD;
&#xD;
          -  RAS (codons 12, 13, 59, 61, 117 and 146 of KRAS and NRAS genes) and BRAF (V600E&#xD;
             mutation) wt status of primary colorectal cancer or related metastasis (local or&#xD;
             central laboratory assessment).&#xD;
&#xD;
          -  Neutrophils ≥1.5 x 109/L, Platelets ≥100 x 109/L, Hgb ≥9 g/dl.&#xD;
&#xD;
          -  Total bilirubin ≤ 1.5 fold the upper-normal limits (UNL), ASAT (SGOT) and/or ALAT&#xD;
             (SGPT) ≤ 2.5 x UNL (or &lt;5 x UNL in the case of liver metastases), alkaline phosphatase&#xD;
             ≤ 2.5 x UNL (or &lt;5 x UNL in case of liver metastases).&#xD;
&#xD;
          -  Creatinine clearance ≥50 mL/min or serum creatinine ≤1.5 x UNL.&#xD;
&#xD;
          -  Male subjects with female partners of childbearing potential must be willing to use&#xD;
             adequate contraception - Contraception, starting with the first dose of study therapy&#xD;
             through 180 days after the last dose of treatment.&#xD;
&#xD;
        Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception&#xD;
        for the subject.&#xD;
&#xD;
          -  Women of childbearing potential must have a negative blood pregnancy test at the&#xD;
             baseline visit&#xD;
&#xD;
          -  Female subjects of childbearing potential must be willing to use an adequate method of&#xD;
             contraception - Contraception, for the course of the study starting with the first&#xD;
             dose of study therapy through 180 days after the last dose of treatment.&#xD;
&#xD;
        Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception&#xD;
        for the subject.&#xD;
&#xD;
          -  Will and ability to comply with the protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous treatment for metastatic disease.&#xD;
&#xD;
          -  Radiotherapy to any site within 4 weeks before the study.&#xD;
&#xD;
          -  Previous adjuvant oxaliplatin-containing chemotherapy.&#xD;
&#xD;
          -  Previous treatment with EGFR inhibitors.&#xD;
&#xD;
          -  Untreated brain metastases or spinal cord compression or primary brain tumours.&#xD;
&#xD;
          -  History or evidence upon physical examination of CNS disease unless adequately&#xD;
             treated.&#xD;
&#xD;
          -  Symptomatic peripheral neuropathy &gt; 1 grade NCIC-CTG criteria.&#xD;
&#xD;
          -  Creatinine clearance &lt; 50 mL/min or serum creatinine &gt;1.5 x UNL.&#xD;
&#xD;
          -  Clinical signs of malnutrition.&#xD;
&#xD;
          -  Neutrophils &lt;1.5 x 109/L, Platelets &lt;100 x 109/L, Hgb &lt;9 g/dl.&#xD;
&#xD;
          -  Diagnosis of interstitial pneumonitis or pulmonary fibrosis.&#xD;
&#xD;
          -  Active uncontrolled infections or other clinically relevant concomitant illness&#xD;
             contraindicating chemotherapy administration.&#xD;
&#xD;
          -  Clinically significant (e.g. active) cardiovascular disease for example&#xD;
             cerebrovascular accidents (≤6 months), myocardial infarction (≤6 months), unstable&#xD;
             angina, New York Heart Association (NYHA) grade II or greater congestive heart failure&#xD;
             (CHF), serious cardiac arrhythmia requiring medication.&#xD;
&#xD;
          -  Treatment with any investigational drug within 30 days prior to enrolment or 2&#xD;
             investigational agent half-lives (whichever is longer)&#xD;
&#xD;
          -  Other co-existing malignancies or malignancies diagnosed within the last 5 years with&#xD;
             the exception of localized basal and squamous cell carcinoma or cervical cancer in&#xD;
             situ.&#xD;
&#xD;
          -  Lack of physical integrity of the upper gastrointestinal tract, malabsorption&#xD;
             syndrome, or inability to take oral medication.&#xD;
&#xD;
          -  Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)&#xD;
             related illness, or hepatitis B or C.&#xD;
&#xD;
          -  Definite contraindications for the use of corticosteroids and antihistamines as&#xD;
             premedication.&#xD;
&#xD;
          -  History of severe allergic reactions or hypersensitivity to trial drugs or any of&#xD;
             their excipients.&#xD;
&#xD;
          -  Any concomitant drugs contraindicated for use with the trial drugs according to the&#xD;
             product information of the pharmaceutical companies.&#xD;
&#xD;
          -  Pregnant or lactating women. Women of childbearing potential with either a positive or&#xD;
             no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at&#xD;
             least 12 months to be considered of non-childbearing potential. Sexually active males&#xD;
             and females (of childbearing potential) unwilling to practice contraception during the&#xD;
             study and until 180 days after the last trial treatment.&#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>Chiara Cremolini, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>U.O. Oncologia Medica 2 Universitaria - Azienda Ospedaliero-Universitaria Pisana Dipartimento di Ricerca Traslazionale e Nuove Tecnologie - Università di Pisa Istituto Toscano Tumori</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fondazione IRCCS Istituto Nazionale Tumori</name>
      <address>
        <city>Milan</city>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS Istituto Oncologico Veneto</name>
      <address>
        <city>Padova</city>
        <zip>35128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O. Universitaria Pisana - Pisa (Pi) Oncologia Medica</name>
      <address>
        <city>Pisa</city>
        <zip>56126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria Integrata Verona</name>
      <address>
        <city>Verona</city>
        <zip>37126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>July 3, 2017</study_first_submitted>
  <study_first_submitted_qc>July 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 27, 2017</study_first_posted>
  <last_update_submitted>January 4, 2023</last_update_submitted>
  <last_update_submitted_qc>January 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 5, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>mFOLFOXIRI + Panitumumab</keyword>
  <keyword>RAS and BRAF wt</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>Leucovorin</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
    <mesh_term>Irinotecan</mesh_term>
    <mesh_term>Panitumumab</mesh_term>
    <mesh_term>Levoleucovorin</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/NCT03231722
org study id: TRIPLETE
nct id: NCT03231722
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
-  The association of FOLFOX (5-fluoruracil, folinic acid, and oxaliplatin) and pan is a
           standard option for the first-line treatment of unresectable RAS and BRAF wt mCRC
           patients.

        -  The phase III TRIBE trial recently demonstrated that FOLFOXIRI (5-fluoruracil, folinic
           acid, oxaliplatin and irinotecan) plus bev significantly prolongs PFS and OS and
           increases RECIST response rate, ETS and DoR, as compared to FOLFIRI (5-fluoruracil
           folinic acid, and irinotecan) plus bev. The advantage provided by the intensification of
           the upfront chemotherapy backbone is independent of RAS and BRAF mutational status.

        -  Some phase II trials recently assessed the safety and activity of the combination of
           three-drugs chemotherapy regimens with an anti-EGFR monoclonal antibody. Promising
           activity results in terms of RECIST response rate and R0 resection rate have been
           achieved, with some safety concerns with special regards to gastrointestinal toxicity.

        -  In the phase II randomized MACBETH study the combination of a modified schedule of
           FOLFOXIRI with cetuximab determined remarkable activity results, with an acceptable and
           manageable safety profile.

        -  The optimal duration of the upfront treatment with chemotherapy plus anti-EGFRs is not
           established. The phase II MACRO-2 trial suggested that interrupting FOLFOX after 4
           months while continuing cet alone as maintenance, is a reasonable option.

        -  Activity parameters (RECIST response rate, ETS, DoR) are clinically relevant endpoints,
           associated with longer survival, in particular with anti-EGFR moAb-based treatment.

      On the basis of these considerations, we designed the present phase III randomized trial of
      first-line mFOLFOXIRI plus pan versus mFOLFOX6 plus pan in RAS and BRAF wt unresectable mCRC
      patients.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: open label
measure: Overall response rate
time frame: 12 months
description: the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria
measure: Overall Toxicity Rate
time frame: 24 months
description: the percentage of patients, relative to the total of enrolled subjects, experiencing any adverse event, according to National Cancer Institute Common Toxicity Criteria (version 4.0)
measure: Toxicity Rate
time frame: 24 months
description: the percentage of patients, relative to the total of enrolled subjects, experiencing a specific adverse event of grade 3/4, according to National Cancer Institute Common Toxicity Criteria (version 4.0)
measure: Progression Free Survival
time frame: 24 months
description: the time from randomization to the first documentation of objective disease progression or death due to any cause, whichever occurs first. Documentation of disease progressive disease is defined as per RECIST 1.1 criteria based on investigator assessment
measure: Overall Survival
time frame: 48 months
description: the time from randomization to the date of death due to any cause
measure: Centrally assessed Overall response rate
time frame: 12 months
description: the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria based on central re-evaluation of CT scan images.
measure: Early Tumour Shrinkage Rate
time frame: up to 2 months from randomization
description: the percentage of patients, relative to the total of the enrolled subjects, achieving a ≥20% decrease in the sum of diameters of RECIST target lesions at week 8 compared to baseline.
measure: Deepness of Response
time frame: 12 months
description: the relative change in the sum of longest diameters of RECIST target lesions at the nadir, in the absence of new lesions or progression of non-target lesions, when compared with baseline.
measure: R0 Resection Rate
time frame: 12 months
description: the percentage of patients, relative to the total of enrolled subjects, undergoing secondary R0 resection of metastases
arm group label: mFOLFOX6 + Panitumab
arm group type: Active Comparator
description: Panitumumab 6 mg/kg iv over 60 minutes, day 1 (if the first infusion is tolerated, then subsequent infusions may be administered over 30 to 60 minutes) followed by
Oxaliplatin 85 mg/sqm iv over 2 hours, day 1 in two-way with
L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by
5-fluorouracil 400 mg/sqm iv bolus, day 1 followed by
5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. If no progression occurs, patients will receive maintenance with 5FU/LV plus pan at the same dose used at the last cycle of the induction treatment. 5FU/LV plus pan will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal. The prosecution of pan until disease progression is recommended also if 5-FU is interrupted because of adverse events, patient's refusal or investigator's choice.
arm group label: mFOLFOXIRI + Panitumumab
arm group type: Experimental
description: Panitumumab 6 mg/kg iv over 60 minutes, day 1 (if the first infusion is tolerated, then subsequent infusions may be administered over 30 to 60 minutes) followed by
Irinotecan 150 mg/sqm iv over 60 minutes day 1, followed by
Oxaliplatin 85 mg/sqm iv over 2 hours day 1, in two-way with
L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by
5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. If no progression occurs, patients will receive maintenance with 5FU/LV plus pan at the same dose used at the last cycle of the induction treatment. 5FU/LV plus pan will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal. The prosecution of pan until disease progression is recommended also if 5-FU is interrupted because of adverse events, patient's refusal or investigator's choice.
intervention type: Drug
intervention name: Panitumumab
description: 6 mg/kg iv over 60 minutes, day 1
arm group label: mFOLFOX6 + Panitumab
arm group label: mFOLFOXIRI + Panitumumab
intervention type: Drug
intervention name: Irinotecan
description: 150 mg/sqm iv over 60 minutes day 1
arm group label: mFOLFOX6 + Panitumab
arm group label: mFOLFOXIRI + Panitumumab
intervention type: Drug
intervention name: Oxaliplatin
description: 85 mg/sqm iv over 2 hours day 1
arm group label: mFOLFOXIRI + Panitumumab
intervention type: Drug
intervention name: l-leucovorin
description: 200 mg/sqm iv over 2 hours
arm group label: mFOLFOX6 + Panitumab
arm group label: mFOLFOXIRI + Panitumumab
intervention type: Drug
intervention name: 5-fluorouracil
description: 400 mg/sqm iv bolus, day 1 followed by 2400 mg/sqm 48 h-continuous infusion, starting on day 1;
arm group label: mFOLFOX6 + Panitumab
arm group label: mFOLFOXIRI + Panitumumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Chiara Cremolini, MD, PhD
role: Study Chair
affiliation: U.O. Oncologia Medica 2 Universitaria - Azienda Ospedaliero-Universitaria Pisana Dipartimento di Ricerca Traslazionale e Nuove Tecnologie - Università di Pisa Istituto Toscano Tumori
facility: 
facility: 
facility: 
facility: 
country: Italy
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Leucovorin
mesh term: Fluorouracil
mesh term: Oxaliplatin
mesh term: Irinotecan
mesh term: Panitumumab
mesh term: Levoleucovorin
sharing ipd: No