<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/NCT03751176</url>
  </required_header>
  <id_info>
    <org_study_id>GEMCAD-17-01</org_study_id>
    <secondary_id>2017-004519-38</secondary_id>
    <nct_id>NCT03751176</nct_id>
  </id_info>
  <brief_title>Second-line FOLFIRI + Panitumumab in Subjects With Wild Type RAS Metastatic Colorectal</brief_title>
  <acronym>BEYOND</acronym>
  <official_title>Phase II Clinical Trial to Evaluate the Efficacy of Second-line FOLFIRI + Panitumumab in Subjects With Wild Type RAS Metastatic Colorectal Cancer Who Have Received FOLFOX + Panitumumab in First-line</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Grupo Espanol Multidisciplinario del Cancer Digestivo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Amgen</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Pivotal S.L.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Grupo Espanol Multidisciplinario del Cancer Digestivo</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>
      To estimate progression-free-survival at 6 months in subjects treated in first-line with&#xD;
      panitumumab and FOLFOX and with wild type RAS mCRC (metastatic colorectal cancer) confirmed&#xD;
      in liquid biopsies before starting second line treatment will be screened for this trial and&#xD;
      who have interrupted panitumumab for &lt;3 months (panitumumab continuation). Control arm of&#xD;
      subjects treated with FOLFIRI alone will be included.&#xD;
&#xD;
      The combinations of 5-fluorouracil (5-FU) with oxaliplatin (FOLFOX)are considered the&#xD;
      backbone chemotherapy for mCRC. Clinical trials have shown the benefit of adding monoclonal&#xD;
      antibodies to subjects without mutations in RAS, directed against the epidermal growth factor&#xD;
      receptor (EGFR) (cetuximab and panitumumab) to conventional chemotherapy as first-line&#xD;
      treatment of mCRC. This trial purposes to study the treatment beyond progression with&#xD;
      panitumumab in subjects treated in first-line with an anti-EGFR monoclonal antibody, or&#xD;
      rather,the re-introduction of the same targeted therapy after progression to first line.&#xD;
&#xD;
      The clinical hypothesis of this study is that the second-line regimen FOLFIRI + panitumumab,&#xD;
      is sufficiently active (defined as a 6-months PFS higher than 30% [based on prior results&#xD;
      with second-line FOLFIRI alone] and of at least 50%), justifying further study in this&#xD;
      population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A phase II, multicentre, open-label, randomized two-arm study. Subjects treated in first-line&#xD;
      with panitumumab and FOLFOX and with wild type RAS mCRC confirmed in liquid biopsies before&#xD;
      starting second line treatment will be screened for this trial. Only subjects who have&#xD;
      interrupted panitumumab for &lt; 3 months (panitumumab continuation) will be included.&#xD;
&#xD;
      Eligible subjects will receive FOLFIRI + panitumumab until disease progression, onset of&#xD;
      unacceptable drug toxicities, or subject/physician's request to discontinue. A control arm of&#xD;
      subjects treated with FOLFIRI alone will be included. Subjects will be assigned in a 3:2&#xD;
      ratio to receive FOLFIRI + panitumumab (Group A) or FOLFIRI alone (Group B). Randomization&#xD;
      will be stratified by primary tumour location (left vs right). A blood sample will be&#xD;
      obtained at baseline and at disease progression in order to determine the mutational status&#xD;
      of RAS/BRAF and other biomarkers.&#xD;
&#xD;
      Tumour response assessment will be performed by the investigator according to Response&#xD;
      Evaluation Criteria in Solid Tumours (RECIST) criteria (version 1.1). Subjects will be&#xD;
      evaluated for tumour response every 8 weeks until documentation of disease progression.&#xD;
      Responding disease will be confirmed no less than 28 days after the criteria for response are&#xD;
      first met. Subjects with symptoms suggestive of progressive disease should be evaluated for&#xD;
      tumour progression at the time the symptoms occur. After second-line treatment&#xD;
      discontinuation, information on subsequent lines of treatments at the physician discretion&#xD;
      and survival will be collected in follow-up visits carried out every 12 weeks (± 4 weeks)&#xD;
      until the end of the study (approximately 20 months after the inclusion of the last subject&#xD;
      in the study).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">November 8, 2018</start_date>
  <completion_date type="Anticipated">November 30, 2022</completion_date>
  <primary_completion_date type="Actual">November 30, 2020</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>Subjects will be assigned in a 3:2 ratio to receive FOLFIRI + panitumumab (Group A) or FOLFIRI alone (Group B). Randomization will be stratified by primary tumour location (left vs right).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression-free survival at 6 months</measure>
    <time_frame>6 months after inclusion</time_frame>
    <description>The proportion of subjects progression free at 6 months</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>38 months</time_frame>
    <description>Time from randomization to progression or death (Kaplan-Meier estimate)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response rate (ORR)</measure>
    <time_frame>38 months</time_frame>
    <description>Proportion of subjects with an objective response (complete or partial response) per RECIST 1.1 criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>38 months</time_frame>
    <description>Time from randomization to the date of death, with participants alive or lost to follow-up at the analysis data cut-off date censored at their last contact date (Kaplan-Meier estimate)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability. ( assessment will consist of monitoring adverse events (AEs), including serious adverse events (SAEs) and laboratory safety parameters)</measure>
    <time_frame>38 months</time_frame>
    <description>Safety assessment will consist of monitoring adverse events (AEs), including serious adverse events (SAEs) and laboratory safety parameters. AEs will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarkers analysis by liquid biopsies.</measure>
    <time_frame>38 months</time_frame>
    <description>Conversion rate of RAS/BRAF status according to liquid biopsy determinations at second-line treatment initiation and at the time of disease progression after second-line treatment</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Colorectal Cancer Metastatic</condition>
  <arm_group>
    <arm_group_label>FOLFIRI + panitumumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients received panitumumab plus FOLFIRI in 14-day cycles until disease progression, unacceptable toxicity, investigator's decision or patient withdrawal of consent, at the following doses:&#xD;
Panitumumab: 6 mg/kg administered by intravenous (IV) infusion over 60 min on days 1 and 14 of every cycle just before administration of chemotherapy&#xD;
FOLFIRI:&#xD;
Irinotecan: 180 mg/m2 as IV infusion over 90 min on day 1&#xD;
Folinic acid: (leucovorin) 200-400 mg/m2 IV over 2 hours on day 1&#xD;
5-FU: 400 mg/m2 bolus followed by 2400 mg/m2 IV continuous infusion over 46-48 hours on days 1 and 2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>FOLFIRI</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients received FOLFIRI in 14-day cycles until disease progression, unacceptable toxicity, investigator's decision or patient withdrawal of consent, at the following doses:&#xD;
Irinotecan: 180 mg/m2 as IV infusion over 90 min on day 1&#xD;
Folinic acid: (leucovorin) 200-400 mg/m2 IV over 2 hours on day 1&#xD;
5-FU: 400 mg/m2 bolus followed by 2400 mg/m2 IV continuous infusion over 46-48 hours on days 1 and 2</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Panitumumab</intervention_name>
    <description>Panitumumab 6 mg/kg will be administered by intravenous (IV) infusion over 60 min on days 1 and 14 of every cycle just before administration of chemotherapy</description>
    <arm_group_label>FOLFIRI + panitumumab</arm_group_label>
    <other_name>Vectibix</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Irinotecan</intervention_name>
    <description>Irinotecan 180 mg/m2 will be administered as IV infusion over 90 min on day 1</description>
    <arm_group_label>FOLFIRI</arm_group_label>
    <arm_group_label>FOLFIRI + panitumumab</arm_group_label>
    <other_name>Any marketed</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Folinic acid</intervention_name>
    <description>Folinic acid 200-400 mg/m2 will be administered as IV infusion over 2 hours on day 1</description>
    <arm_group_label>FOLFIRI</arm_group_label>
    <arm_group_label>FOLFIRI + panitumumab</arm_group_label>
    <other_name>Any marketed</other_name>
    <other_name>Leucovorin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5-FU</intervention_name>
    <description>5-FU will be administered IV 400 mg/m2 bolus followed by 2400 mg/m2 IV continuous infusion over 46-48 hours on days 1 and 2</description>
    <arm_group_label>FOLFIRI</arm_group_label>
    <arm_group_label>FOLFIRI + panitumumab</arm_group_label>
    <other_name>Any marketed</other_name>
    <other_name>5-fluorouracil</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Man or woman at least 18 years old&#xD;
&#xD;
          2. Capable of understand, sign and date an informed consent approved by an IEC&#xD;
             (investigational Ethics Committee)&#xD;
&#xD;
          3. Histologically confirmed adenocarcinoma of the colon or rectum in subjects with&#xD;
             metastatic disease&#xD;
&#xD;
          4. Having received a 1st line chemotherapy regimen for mCRC consisting of FOLFOX +&#xD;
             panitumumab and having at least achieved stable disease ( i.e., CR (Complete Response)&#xD;
             PR (Partial Response) or SD (stable disease) )&#xD;
&#xD;
          5. Wild-type RAS tumour status confirmed in liquid biopsies before starting second-line&#xD;
             treatment&#xD;
&#xD;
          6. At least one unidimensionally measurable lesion of at least 10 mm per RECIST criteria&#xD;
             (version 1.1)&#xD;
&#xD;
          7. Subjects not candidates for metastasectomy&#xD;
&#xD;
          8. Tumour disease staging according to RECIST (version 1.1) by investigator up to 4 weeks&#xD;
             prior to start of study treatment&#xD;
&#xD;
          9. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2&#xD;
&#xD;
         10. Adequate bone marrow function: neutrophils ≥1.5 x109/ L; platelets ≥100 x109/L;&#xD;
             haemoglobin ≥9 g/dL&#xD;
&#xD;
         11. Hepatic, renal and metabolic function as follows:&#xD;
&#xD;
               -  Total bilirubin count ≤1.5 x upper limit of normal (ULN), ALT (alanine&#xD;
                  aminotransferase) and AST (aspartate aminotransferase) &lt;2.5 x ULN; or in case of&#xD;
                  liver metastasis ALT and AST &lt;5 x ULN&#xD;
&#xD;
               -  Renal function, calculated as creatinine clearance or 24-hour creatinine&#xD;
                  clearance ≥ 50 mL/min&#xD;
&#xD;
               -  Magnesium &gt; lower limit of normal (LLN) -&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Diagnosis of progressive disease more than 3 months after the last panitumumab&#xD;
             administration&#xD;
&#xD;
          2. First-line PFS of less than 3 months&#xD;
&#xD;
          3. Subjects given less than 3 months (consecutive) of first-line panitumumab&#xD;
&#xD;
          4. History of prior or concurrent central nervous system (CNS) metastases&#xD;
&#xD;
          5. History of another primary cancer, except: curatively treated in situ cervical cancer,&#xD;
             or curatively resected non-melanoma skin cancer, or other primary solid tumour&#xD;
             curatively treated with no known active disease present and no treatment administered&#xD;
             for ≥ 5 years before inclusion&#xD;
&#xD;
          6. Prior irinotecan therapy&#xD;
&#xD;
          7. Unresolved toxicities of a previous systemic treatment that, in the opinion of the&#xD;
             investigator, cause the subject unfit for inclusion&#xD;
&#xD;
          8. Prior hormonal therapy, immunotherapy or approved or experimental antibody/proteins ≤&#xD;
             30 days before inclusion (excluding panitumumab)&#xD;
&#xD;
          9. Any investigational agent within 30 days prior to inclusion&#xD;
&#xD;
         10. Evidence of previous acute hypersensitivity reaction, of any grade, to any component&#xD;
             of the treatment&#xD;
&#xD;
         11. History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial&#xD;
             pneumonitis or pulmonary fibrosis on baseline chest computerised tomography&#xD;
&#xD;
         12. Acute or subacute intestinal occlusion and/or active inflammatory bowel disease or&#xD;
             other bowel disease that causes chronic diarrhoea (defined as grade ≥ 2 diarrhoea&#xD;
             according to Common Terminology Criteria for Adverse Events (CTCAE) v 4.03)&#xD;
&#xD;
         13. Significant cardiovascular disease including unstable angina or myocardial infarction&#xD;
             within 12 months before initiating study treatment or a history of ventricular&#xD;
             arrhythmia&#xD;
&#xD;
         14. History of Gilbert disease or known dihydropyrimidine deficiency syndrome&#xD;
&#xD;
         15. Known positive test for human immunodeficiency virus infection, hepatitis C virus,&#xD;
             chronic active hepatitis B infection&#xD;
&#xD;
         16. Treatment for systemic infection within 14 days before the start of study treatment&#xD;
&#xD;
         17. History of any disease that may increase the risks associated with study participation&#xD;
             or may interfere with the interpretation of study results&#xD;
&#xD;
         18. Surgery (excluding diagnostic biopsy or placement of a central venous catheter) and/or&#xD;
             radiotherapy within 28 days prior to inclusion in the study.&#xD;
&#xD;
         19. Pregnant or breastfeeding woman&#xD;
&#xD;
         20. Male or female of childbearing age who do not agree with taking adequate contraceptive&#xD;
             precautions, i.e. use contraception double barrier (e.g., diaphragm plus condoms) or&#xD;
             abstinence during the course of the study and for 6 months after the last&#xD;
             administration of study drug for women and 1 month for men&#xD;
&#xD;
         21. The subject is unwilling or unable to meet the requirements of the study&#xD;
&#xD;
         22. Psychological, geographical, familial or sociological conditions that potentially&#xD;
             prevent compliance with the study protocol and follow-up schedule. These conditions&#xD;
             should be discussed with the subject before inclusion in the trial. -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jorge Aparicio, MD</last_name>
    <role>Study Director</role>
    <affiliation>Hospital universitari i Politecnic La Fe</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ICO Girona Dr. Josep Trueta</name>
      <address>
        <city>Gerona</city>
        <state>Barcelona</state>
        <zip>17007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Granollers</name>
      <address>
        <city>Granollers</city>
        <state>Barcelona</state>
        <zip>08402</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Mutua de Terrassa</name>
      <address>
        <city>Terrassa</city>
        <state>Barcelona</state>
        <zip>08221</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario de Elche</name>
      <address>
        <city>Alicante</city>
        <state>Elche</state>
        <zip>03203</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Fundación Alcorcón</name>
      <address>
        <city>Alcorcón</city>
        <state>Madrid</state>
        <zip>28922</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>H. Universitari Sant Joan de Reus</name>
      <address>
        <city>Reus</city>
        <state>Tarragona</state>
        <zip>43204</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de La Ribera de Alzira</name>
      <address>
        <city>Alzira</city>
        <state>Valencia</state>
        <zip>46600</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clínic de Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de la Santa Creu I Sant Pau</name>
      <address>
        <city>Barcelona</city>
        <zip>08041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital 12 de Octubre</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universtiario la Paz</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CIOCC Sanchinarro</name>
      <address>
        <city>Madrid</city>
        <zip>28050</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complejo Hospitalario de Navarra</name>
      <address>
        <city>Navarro</city>
        <zip>31008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Corporació Sanitaria Parc Taulí</name>
      <address>
        <city>Sabadell</city>
        <zip>08208</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundación Instituto Valenciano de Oncología</name>
      <address>
        <city>Valencia</city>
        <zip>46009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Dr. Peset</name>
      <address>
        <city>Valencia</city>
        <zip>46017</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario y Politécnico La Fe</name>
      <address>
        <city>Valencia</city>
        <zip>46026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <link>
    <url>http://www.gemcad.es/</url>
    <description>GEMCAD (Grupo Español Multidisciplinar en Cancer Digestivo) web page</description>
  </link>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>November 20, 2018</study_first_submitted>
  <study_first_submitted_qc>November 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 23, 2018</study_first_posted>
  <last_update_submitted>June 29, 2021</last_update_submitted>
  <last_update_submitted_qc>June 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 30, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Clinical trial, phase II</keyword>
  <keyword>Aged (at least 18 years old)</keyword>
  <keyword>Progression -Free - Survival</keyword>
  <keyword>Safety</keyword>
  <keyword>Conversion rate of RAS/BRAF status in liquid biopsy</keyword>
  <keyword>Chemotherapy regimen</keyword>
  <keyword>Monoclonal antibody</keyword>
  <keyword>FOLFIRI</keyword>
  <keyword>Panitumumab</keyword>
  <keyword>RAS/BRAF Wild-type</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>Folic Acid</mesh_term>
    <mesh_term>Fluorouracil</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/NCT03751176
org study id: GEMCAD-17-01
secondary id: 2017-004519-38
nct id: NCT03751176
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
To estimate progression-free-survival at 6 months in subjects treated in first-line with
      panitumumab and FOLFOX and with wild type RAS mCRC (metastatic colorectal cancer) confirmed
      in liquid biopsies before starting second line treatment will be screened for this trial and
      who have interrupted panitumumab for <3 months (panitumumab continuation). Control arm of
      subjects treated with FOLFIRI alone will be included.

      The combinations of 5-fluorouracil (5-FU) with oxaliplatin (FOLFOX)are considered the
      backbone chemotherapy for mCRC. Clinical trials have shown the benefit of adding monoclonal
      antibodies to subjects without mutations in RAS, directed against the epidermal growth factor
      receptor (EGFR) (cetuximab and panitumumab) to conventional chemotherapy as first-line
      treatment of mCRC. This trial purposes to study the treatment beyond progression with
      panitumumab in subjects treated in first-line with an anti-EGFR monoclonal antibody, or
      rather,the re-introduction of the same targeted therapy after progression to first line.

      The clinical hypothesis of this study is that the second-line regimen FOLFIRI + panitumumab,
      is sufficiently active (defined as a 6-months PFS higher than 30% [based on prior results
      with second-line FOLFIRI alone] and of at least 50%), justifying further study in this
      population.
A phase II, multicentre, open-label, randomized two-arm study. Subjects treated in first-line
      with panitumumab and FOLFOX and with wild type RAS mCRC confirmed in liquid biopsies before
      starting second line treatment will be screened for this trial. Only subjects who have
      interrupted panitumumab for < 3 months (panitumumab continuation) will be included.

      Eligible subjects will receive FOLFIRI + panitumumab until disease progression, onset of
      unacceptable drug toxicities, or subject/physician's request to discontinue. A control arm of
      subjects treated with FOLFIRI alone will be included. Subjects will be assigned in a 3:2
      ratio to receive FOLFIRI + panitumumab (Group A) or FOLFIRI alone (Group B). Randomization
      will be stratified by primary tumour location (left vs right). A blood sample will be
      obtained at baseline and at disease progression in order to determine the mutational status
      of RAS/BRAF and other biomarkers.

      Tumour response assessment will be performed by the investigator according to Response
      Evaluation Criteria in Solid Tumours (RECIST) criteria (version 1.1). Subjects will be
      evaluated for tumour response every 8 weeks until documentation of disease progression.
      Responding disease will be confirmed no less than 28 days after the criteria for response are
      first met. Subjects with symptoms suggestive of progressive disease should be evaluated for
      tumour progression at the time the symptoms occur. After second-line treatment
      discontinuation, information on subsequent lines of treatments at the physician discretion
      and survival will be collected in follow-up visits carried out every 12 weeks (± 4 weeks)
      until the end of the study (approximately 20 months after the inclusion of the last subject
      in the study).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Subjects will be assigned in a 3:2 ratio to receive FOLFIRI + panitumumab (Group A) or FOLFIRI alone (Group B). Randomization will be stratified by primary tumour location (left vs right).
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free survival at 6 months
time frame: 6 months after inclusion
description: The proportion of subjects progression free at 6 months
measure: Progression-free survival (PFS)
time frame: 38 months
description: Time from randomization to progression or death (Kaplan-Meier estimate)
measure: Overall response rate (ORR)
time frame: 38 months
description: Proportion of subjects with an objective response (complete or partial response) per RECIST 1.1 criteria
measure: Overall survival (OS)
time frame: 38 months
description: Time from randomization to the date of death, with participants alive or lost to follow-up at the analysis data cut-off date censored at their last contact date (Kaplan-Meier estimate)
measure: Safety and tolerability. ( assessment will consist of monitoring adverse events (AEs), including serious adverse events (SAEs) and laboratory safety parameters)
time frame: 38 months
description: Safety assessment will consist of monitoring adverse events (AEs), including serious adverse events (SAEs) and laboratory safety parameters. AEs will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
measure: Biomarkers analysis by liquid biopsies.
time frame: 38 months
description: Conversion rate of RAS/BRAF status according to liquid biopsy determinations at second-line treatment initiation and at the time of disease progression after second-line treatment
arm group label: FOLFIRI + panitumumab
arm group type: Experimental
description: Patients received panitumumab plus FOLFIRI in 14-day cycles until disease progression, unacceptable toxicity, investigator's decision or patient withdrawal of consent, at the following doses:
Panitumumab: 6 mg/kg administered by intravenous (IV) infusion over 60 min on days 1 and 14 of every cycle just before administration of chemotherapy
FOLFIRI:
Irinotecan: 180 mg/m2 as IV infusion over 90 min on day 1
Folinic acid: (leucovorin) 200-400 mg/m2 IV over 2 hours on day 1
5-FU: 400 mg/m2 bolus followed by 2400 mg/m2 IV continuous infusion over 46-48 hours on days 1 and 2
arm group label: FOLFIRI
arm group type: Active Comparator
description: Patients received FOLFIRI in 14-day cycles until disease progression, unacceptable toxicity, investigator's decision or patient withdrawal of consent, at the following doses:
Irinotecan: 180 mg/m2 as IV infusion over 90 min on day 1
Folinic acid: (leucovorin) 200-400 mg/m2 IV over 2 hours on day 1
5-FU: 400 mg/m2 bolus followed by 2400 mg/m2 IV continuous infusion over 46-48 hours on days 1 and 2
intervention type: Drug
intervention name: Panitumumab
description: Panitumumab 6 mg/kg will be administered by intravenous (IV) infusion over 60 min on days 1 and 14 of every cycle just before administration of chemotherapy
arm group label: FOLFIRI + panitumumab
other name: Vectibix
intervention type: Drug
intervention name: Irinotecan
description: Irinotecan 180 mg/m2 will be administered as IV infusion over 90 min on day 1
arm group label: FOLFIRI
arm group label: FOLFIRI + panitumumab
other name: Any marketed
intervention type: Drug
intervention name: Folinic acid
description: Folinic acid 200-400 mg/m2 will be administered as IV infusion over 2 hours on day 1
arm group label: FOLFIRI
arm group label: FOLFIRI + panitumumab
other name: Any marketed
other name: Leucovorin
intervention type: Drug
intervention name: 5-FU
description: 5-FU will be administered IV 400 mg/m2 bolus followed by 2400 mg/m2 IV continuous infusion over 46-48 hours on days 1 and 2
arm group label: FOLFIRI
arm group label: FOLFIRI + panitumumab
other name: Any marketed
other name: 5-fluorouracil
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Jorge Aparicio, MD
role: Study Director
affiliation: Hospital universitari i Politecnic La Fe
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country: Spain
url: http://www.gemcad.es/
description: GEMCAD (Grupo Español Multidisciplinar en Cancer Digestivo) web page
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Leucovorin
mesh term: Folic Acid
mesh term: Fluorouracil
mesh term: Irinotecan
mesh term: Panitumumab
mesh term: Levoleucovorin
sharing ipd: No