<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/NCT01670721</url>
  </required_header>
  <id_info>
    <org_study_id>AFLIBL06266</org_study_id>
    <secondary_id>2012-000048-89</secondary_id>
    <secondary_id>U1111-1128-9325</secondary_id>
    <nct_id>NCT01670721</nct_id>
  </id_info>
  <brief_title>Colorectal Cancer Metastatic</brief_title>
  <acronym>AFEQT</acronym>
  <official_title>A Multicenter, Single Arm, Open Label Clinical Trial Evaluating Safety and Health Related Quality of Life of Aflibercept in Combination With Irinotecan/5-FU Chemotherapy (FOLFIRI) in Patients With Metastatic Colorectal Cancer (mCRC) Previously Treated With an Oxaliplatin-Containing Regimen</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Regeneron Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Sanofi</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary Objective:&#xD;
&#xD;
      To evaluate the safety of aflibercept in participants with mCRC treated with&#xD;
      irinotecan/5-Fluorouracil (5-FU) combination (FOLFIRI) after failure of an oxaliplatin-based&#xD;
      regimen (participants similar to those evaluated in the VELOUR trial [EFC10262, NCT00561470])&#xD;
      according to side effects prevention and management guidelines.&#xD;
&#xD;
      Secondary Objective:&#xD;
&#xD;
      To document the Health-Related Quality of Life (HRQL) of aflibercept in this participant&#xD;
      population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Each participant was treated until disease progression (DP), unacceptable toxicity, death,&#xD;
      Investigator's decision or participant's refusal for further treatment (whichever come&#xD;
      first). Participants were followed-up during treatment and for at least 30 days after its&#xD;
      last study treatment (either Aflibercept or FOLFIRI) administration, up to a maximum of 6&#xD;
      months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">June 2015</completion_date>
  <primary_completion_date type="Actual">June 2015</primary_completion_date>
  <phase>Phase 3</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>Percentage of Participants With Adverse Events (AEs)</measure>
    <time_frame>Baseline upto 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure:723 days)</time_frame>
    <description>Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period. On-treatment period was defined as the time from the first dose of treatment to 30 days after the last dose of treatment (either Aflibercept or FOLFIRI). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment for Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)</measure>
    <time_frame>Pre-dose at Baseline, Day 1 of every odd cycle; and at end of treatment (30 days after last study treatment) (maximum exposure: 99 weeks)</time_frame>
    <description>EORTC-QLQ-C30 is a cancer-specific instrument with 30 questions for evaluation of new chemotherapy and provides an assessment of participant reported outcome dimensions. First 28 questions used 4-point scale (1=not at all,2=a little,3=quite a bit,4=very much) for evaluating 5 functional scales (physical,role,emotional,cognitive,social), 3 symptom scales (fatigue,nausea/vomiting,pain) &amp; other single items. For each item,high score represented high level of symptomatology/problem. Last 2 questions represented participant's assessment of overall health &amp; quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 observed values and change from baseline for global health status (scoring of questions 29 &amp; 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28). Answers were converted into grading scale, with values between 0 and 100. A high score represented a favorable outcome with a best quality of life for participant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in HRQL European-Quality of Life-5 Dimension Instrument-3 Levels (EQ-5D-3L) Index Score</measure>
    <time_frame>Pre-dose at Baseline, Day 1 of every odd cycle; and at end of treatment (30 days after last study treatment) (maximum exposure: 99 weeks)</time_frame>
    <description>EQ-5D was a standardized HRQL questionnaire consisting of EQ-5D descriptive system and Visual Analogue Scale (VAS). EQ-5D descriptive system comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression measured on 3 levels (no problem, some problems &amp; severe problems) within a particular EQ-5D dimension. 5 dimensional 3-level system was converted into single index utility score. Possible values for single index utility score ranged from -0.594 (severe problems in all dimensions) to 1.0 (no problem in all dimensions) on scale where 1 represented best possible health state.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in HRQL EQ-5D-3L VAS Score</measure>
    <time_frame>Pre-dose at Baseline, Day 1 of every odd cycle; and at end of treatment (30 days after last study treatment) (maximum exposure: 99 weeks)</time_frame>
    <description>EQ-5D VAS was used to record a participant's rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 = worst imaginable health state and 100 = best imaginable health state. Baseline corresponded to last evaluable assessment before treatment administration.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">175</enrollment>
  <condition>Colorectal Cancer Metastatic</condition>
  <arm_group>
    <arm_group_label>Aflibercept + FOLFIRI (Irinotecan, 5-FU &amp; Leucovorin)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Aflibercept 4 mg/kg intravenous (IV) infusion over 60 minutes followed by Irinotecan 180 mg/m^2 IV infusion over 90 minutes and Leucovorin 400 mg/m^2 IV infusion over 120 minutes at the same time followed by 5-FU 400 mg/m^2 IV bolus over 2-4 minutes followed by 5-FU 2400 mg/m^2 continuous IV infusion over 46 hours on Day 1 of each cycle (1 Cycle = 2 weeks), until DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AFLIBERCEPT</intervention_name>
    <description>Pharmaceutical form:Concentrate for solution for infusion; Route of administration: Intravenous</description>
    <arm_group_label>Aflibercept + FOLFIRI (Irinotecan, 5-FU &amp; Leucovorin)</arm_group_label>
    <other_name>AVE0005</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Irinotecan</intervention_name>
    <description>Pharmaceutical form:Concentrate for solution for infusion; Route of administration: Intravenous</description>
    <arm_group_label>Aflibercept + FOLFIRI (Irinotecan, 5-FU &amp; Leucovorin)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluorouracil</intervention_name>
    <description>Pharmaceutical form:Concentrate for solution for infusion; Route of administration: Intravenous</description>
    <arm_group_label>Aflibercept + FOLFIRI (Irinotecan, 5-FU &amp; Leucovorin)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Leucovorin</intervention_name>
    <description>Pharmaceutical form:Concentrate for solution for infusion; Route of administration: Intravenous</description>
    <arm_group_label>Aflibercept + FOLFIRI (Irinotecan, 5-FU &amp; Leucovorin)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Histologically or cytologically proven adenocarcinoma of the colon or rectum.&#xD;
&#xD;
          -  Metastatic disease.&#xD;
&#xD;
          -  Age ≥18 years.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.&#xD;
&#xD;
          -  One and only one prior chemotherapeutic regimen for metastatic disease. This prior&#xD;
             chemotherapy must be an oxaliplatin containing regimen. Participants must progressed&#xD;
             during or following the last administration of the oxaliplatin based chemotherapy.&#xD;
             Participants relapsing within 6 months of completion of oxaliplatin adjuvant&#xD;
             chemotherapy were also eligible.&#xD;
&#xD;
          -  Participants must be affiliated to a Social Security System.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
        Related to Methodology&#xD;
&#xD;
          -  Prior therapy with irinotecan; Absolute neutrophil counts (ANC) &lt;1.5 x 109/L; Platelet&#xD;
             count &lt;100 x 109/L; Hemoglobin &lt;9.0 g/dL; Total bilirubin &gt;1.5 x upper limit of normal&#xD;
             (ULN); Transaminases &gt;3 x ULN (unless liver metastasis are present, 5 x ULN in that&#xD;
             case); Alkaline phosphatase &gt;3 x ULN (unless liver metastasis are present, 5 x ULN in&#xD;
             that case).&#xD;
&#xD;
          -  Less than 4 weeks elapsed from prior radiotherapy or prior chemotherapy or major&#xD;
             surgery to the time of inclusion or until the surgical wound was fully healed&#xD;
             whichever came later (48 hours in case of minor surgical procedure or until wound full&#xD;
             healing observed).&#xD;
&#xD;
          -  Treatment with any investigational drug within 30 days prior to inclusion.&#xD;
&#xD;
          -  AEs (with exception of alopecia, peripheral sensory neuropathy and those listed in&#xD;
             specific exclusion criteria) from any prior anti cancer therapy of grade &gt;1 National&#xD;
             Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v.4.0 at&#xD;
             the time of inclusion.&#xD;
&#xD;
          -  History of brain metastases, uncontrolled spinal cord compression, or carcinomatous&#xD;
             meningitis or new evidence of brain or leptomeningeal disease.&#xD;
&#xD;
          -  Other prior malignancy. Basal cell or squamous cell skin cancer, carcinoma in situ of&#xD;
             the cervix or any other cancer from which the participant had been disease free for &gt;5&#xD;
             years were allowed.&#xD;
&#xD;
          -  Any of the following within 6 months prior to inclusion: myocardial infarction,&#xD;
             severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York&#xD;
             Heart Association (NYHA) class III or IV congestive heart failure, stroke or transient&#xD;
             ischemic attack.&#xD;
&#xD;
          -  Any of the following within 3 months prior to inclusion: Grade 3-4 gastrointestinal&#xD;
             bleeding/hemorrhage, treatment resistant peptic ulcer disease, erosive oesophagitis or&#xD;
             gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary&#xD;
             embolism or other uncontrolled thromboembolic event.&#xD;
&#xD;
          -  Occurrence of deep vein thrombosis within 4 weeks, prior to inclusion.&#xD;
&#xD;
          -  Known acquired immunodeficiency syndrome (AIDS)-related illnesses or known human&#xD;
             deficiency virus (HIV) disease requiring antiretroviral treatment.&#xD;
&#xD;
          -  Any severe acute or chronic medical condition, which could impair the ability of the&#xD;
             participant to participate to the study or to interfere with interpretation of study&#xD;
             results.&#xD;
&#xD;
          -  Pregnant or breast-feeding women. Positive pregnancy test for women of reproductive&#xD;
             potential.&#xD;
&#xD;
          -  Participants with reproductive potential (female and male) who did not agree to use a&#xD;
             method of contraception during the study treatment period and for at least 6 months&#xD;
             following completion of study treatment. The definition of effective method was left&#xD;
             to the investigator's judgment.&#xD;
&#xD;
        Related to Aflibercept:&#xD;
&#xD;
          -  Urine protein-creatinine ratio (UPCR) &gt;1 on morning spot urinalysis or proteinuria &gt;&#xD;
             500 mg/24-h.&#xD;
&#xD;
          -  Serum creatinine &gt;1.5 x ULN . If creatinine 1.0-1.5 x ULN, creatinine clearance,&#xD;
             calculated according to Cockroft-Gault formula, &lt;60 ml/min will exclude the&#xD;
             participant.&#xD;
&#xD;
          -  Uncontrolled hypertension (blood pressure &gt;140/90 mmHg or systolic blood pressure &gt;160&#xD;
             mmHg when diastolic blood pressure &lt;90 mmHg, on at least 2 repeated determinations on&#xD;
             separate days, or upon clinical judgement within 3 months prior to study inclusion.&#xD;
&#xD;
          -  Participants on anticoagulant therapy with unstable dose of warfarin and/or having an&#xD;
             out-of-therapeutic range international normalized ratio (INR) (&gt;3) within the 4 weeks&#xD;
             prior to inclusion.&#xD;
&#xD;
          -  Evidence of clinically significant bleeding diathesis or underlying coagulopathy (e.g.&#xD;
             INR &gt;1.5 without vitamine K antagonist therapy), non-healing wound.&#xD;
&#xD;
        Related to FOLFIRI&#xD;
&#xD;
          -  Known dihydropyrimidine dehydrogenase deficiency.&#xD;
&#xD;
          -  Predisposing colonic or small bowel disorders in which the symptoms were uncontrolled&#xD;
             as indicated by baseline of &gt;3 loose stools daily.&#xD;
&#xD;
          -  Prior history of chronic enteropathy, inflammatory enteropathy, chronic diarrhea,&#xD;
             unresolved bowel obstruction/sub-obstruction, more than hemicolectomy, extensive small&#xD;
             intestine resection with chronic diarrhea.&#xD;
&#xD;
          -  History of anaphylaxis or known intolerance to atropine sulphate or loperamide or&#xD;
             appropriate antiemetics to be administered in conjunction with FOLFIRI.&#xD;
&#xD;
          -  Treatment with concomitant anticonvulsivant agents that are cytochrome P450 3A4&#xD;
             (CYP3A4) inducers (phenytoin, phenobarbital, carbamazepine), unless discontinued &gt;7&#xD;
             days.&#xD;
&#xD;
          -  Participants with known Gilbert's syndrome.&#xD;
&#xD;
        The above information was not intended to contain all considerations relevant to a&#xD;
        participant's potential participation in a clinical trial.&#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_official>
    <last_name>Clinical Sciences &amp; Operations</last_name>
    <role>Study Director</role>
    <affiliation>Sanofi</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Administrative office</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>October 2016</verification_date>
  <study_first_submitted>July 13, 2012</study_first_submitted>
  <study_first_submitted_qc>August 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 22, 2012</study_first_posted>
  <results_first_submitted>June 8, 2016</results_first_submitted>
  <results_first_submitted_qc>October 4, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">November 28, 2016</results_first_posted>
  <last_update_submitted>October 4, 2016</last_update_submitted>
  <last_update_submitted_qc>October 4, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 28, 2016</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>Fluorouracil</mesh_term>
    <mesh_term>Irinotecan</mesh_term>
    <mesh_term>Aflibercept</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was conducted at 38 sites in France. A total of 182 participants were screened between 08 August 2012 and 30 June 2014, out of which 175 participants were enrolled and treated.</recruitment_details>
      <pre_assignment_details>Participants enrolled in the study to assess the safety of Aflibercept in participants treated with a combination of Aflibercept with FOLFIRI regimen (Irinotecan, Leucovorin and 5-Fluorouracil [5-FU]).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Aflibercept + FOLFIRI (Irinotecan, 5-FU &amp; Leucovorin)</title>
          <description>Aflibercept 4 mg/kg intravenous (IV) infusion over 60 minutes followed by Irinotecan 180 mg/m^2 IV infusion over 90 minutes and Leucovorin 400 mg/m^2 IV infusion over 120 minutes at the same time followed by 5-FU 400 mg/m^2 IV bolus over 2-4 minutes followed by 5-FU 2400 mg/m^2 continuous IV infusion over 46 hours on Day 1 of each cycle (1 Cycle = 2 weeks), until disease progression (DP), unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="175"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="122">81 participants with DP and 41 with adverse events were considered as completed.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="53"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Participant's decision</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other than specified above</title>
              <participants_list>
                <participants group_id="P1" count="38"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Aflibercept + FOLFIRI (Irinotecan, 5-FU &amp; Leucovorin)</title>
          <description>Aflibercept 4 mg/kg IV infusion over 60 minutes followed by Irinotecan 180 mg/m^2 IV infusion over 90 minutes and Leucovorin 400 mg/m^2 IV infusion over 120 minutes at the same time followed by 5-FU 400 mg/m^2 IV bolus over 2-4 minutes followed by 5-FU 2400 mg/m^2 continuous IV infusion over 46 hours on Day 1 of each cycle (1 Cycle = 2 weeks), until DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="175"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="64.5" spread="11.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="77"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Adverse Events (AEs)</title>
        <description>Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period. On-treatment period was defined as the time from the first dose of treatment to 30 days after the last dose of treatment (either Aflibercept or FOLFIRI). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.</description>
        <time_frame>Baseline upto 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure:723 days)</time_frame>
        <population>Safety population defined as the participants who signed the informed consent form and received at least part of one dose of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept + FOLFIRI (Irinotecan, 5-FU &amp; Leucovorin)</title>
            <description>Aflibercept 4 mg/kg IV infusion over 60 minutes followed by Irinotecan 180 mg/m^2 IV infusion over 90 minutes and Leucovorin 400 mg/m^2 IV infusion over 120 minutes at the same time followed by 5-FU 400 mg/m^2 IV bolus over 2-4 minutes followed by 5-FU 2400 mg/m^2 continuous IV infusion over 46 hours on Day 1 of each cycle (1 Cycle = 2 weeks), until DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Adverse Events (AEs)</title>
          <description>Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period. On-treatment period was defined as the time from the first dose of treatment to 30 days after the last dose of treatment (either Aflibercept or FOLFIRI). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.</description>
          <population>Safety population defined as the participants who signed the informed consent form and received at least part of one dose of study treatment.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="175"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any serious TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any serious related TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any TEAE leading to death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any TEAE (permanent treatment discontinuation)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any TEAE (premature treatment discontinuation)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment for Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)</title>
        <description>EORTC-QLQ-C30 is a cancer-specific instrument with 30 questions for evaluation of new chemotherapy and provides an assessment of participant reported outcome dimensions. First 28 questions used 4-point scale (1=not at all,2=a little,3=quite a bit,4=very much) for evaluating 5 functional scales (physical,role,emotional,cognitive,social), 3 symptom scales (fatigue,nausea/vomiting,pain) &amp; other single items. For each item,high score represented high level of symptomatology/problem. Last 2 questions represented participant's assessment of overall health &amp; quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 observed values and change from baseline for global health status (scoring of questions 29 &amp; 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28). Answers were converted into grading scale, with values between 0 and 100. A high score represented a favorable outcome with a best quality of life for participant.</description>
        <time_frame>Pre-dose at Baseline, Day 1 of every odd cycle; and at end of treatment (30 days after last study treatment) (maximum exposure: 99 weeks)</time_frame>
        <population>EORTC QLQ-C30 analysis population: participants who signed informed consent form; had an evaluable QLQ-C30 questionnaire at baseline and at least one evaluable assessment post baseline and received at least part of one dose of study treatment(either Aflibercept or FOLFIRI).Here, n=number of participants with available data at specified time-points.</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept + FOLFIRI (Irinotecan, 5-FU &amp; Leucovorin)</title>
            <description>Aflibercept 4 mg/kg IV infusion over 60 minutes followed by Irinotecan 180 mg/m^2 IV infusion over 90 minutes and Leucovorin 400 mg/m^2 IV infusion over 120 minutes at the same time followed by 5-FU 400 mg/m^2 IV bolus over 2-4 minutes followed by 5-FU 2400 mg/m^2 continuous IV infusion over 46 hours on Day 1 of each cycle (1 Cycle = 2 weeks), until DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment for Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)</title>
          <description>EORTC-QLQ-C30 is a cancer-specific instrument with 30 questions for evaluation of new chemotherapy and provides an assessment of participant reported outcome dimensions. First 28 questions used 4-point scale (1=not at all,2=a little,3=quite a bit,4=very much) for evaluating 5 functional scales (physical,role,emotional,cognitive,social), 3 symptom scales (fatigue,nausea/vomiting,pain) &amp; other single items. For each item,high score represented high level of symptomatology/problem. Last 2 questions represented participant's assessment of overall health &amp; quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 observed values and change from baseline for global health status (scoring of questions 29 &amp; 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28). Answers were converted into grading scale, with values between 0 and 100. A high score represented a favorable outcome with a best quality of life for participant.</description>
          <population>EORTC QLQ-C30 analysis population: participants who signed informed consent form; had an evaluable QLQ-C30 questionnaire at baseline and at least one evaluable assessment post baseline and received at least part of one dose of study treatment(either Aflibercept or FOLFIRI).Here, n=number of participants with available data at specified time-points.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="152"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (n=148)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="69.54" spread="18.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 3 (n=130)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.56" spread="19.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 5 (n=99)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.86" spread="19.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 7 (n=72)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.22" spread="20.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 9 (n=51)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.31" spread="19.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 11 (n=45)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-14.81" spread="21.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 13 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-12.67" spread="24.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 15 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-12.50" spread="18.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 17 (n=14)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-14.29" spread="15.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 19 (n=12)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.28" spread="11.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 21 (n=10)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.83" spread="19.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 23 (n=6)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.72" spread="20.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 25 (n=4)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.33" spread="6.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 27 (n=4)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-12.50" spread="15.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 29 (n=2)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.33" spread="11.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 31 (n=2)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-16.67" spread="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 33 (n=1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="NA">As only one participant was analyzed at cycle 33, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 35 (n=1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="NA">As only one participant was analyzed at cycle 35, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 37 (n=2)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.33" spread="11.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 39 (n=2)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.33" spread="11.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 41 (n=2)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.33" spread="11.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 43 (n=2)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-12.50" spread="5.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 45 (n=2)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.17" spread="17.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 47 (n=1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="NA">As only one participant was analyzed at cycle 47, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At end of study treatment (n=73)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.19" spread="24.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in HRQL European-Quality of Life-5 Dimension Instrument-3 Levels (EQ-5D-3L) Index Score</title>
        <description>EQ-5D was a standardized HRQL questionnaire consisting of EQ-5D descriptive system and Visual Analogue Scale (VAS). EQ-5D descriptive system comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression measured on 3 levels (no problem, some problems &amp; severe problems) within a particular EQ-5D dimension. 5 dimensional 3-level system was converted into single index utility score. Possible values for single index utility score ranged from -0.594 (severe problems in all dimensions) to 1.0 (no problem in all dimensions) on scale where 1 represented best possible health state.</description>
        <time_frame>Pre-dose at Baseline, Day 1 of every odd cycle; and at end of treatment (30 days after last study treatment) (maximum exposure: 99 weeks)</time_frame>
        <population>EQ-5D analysis population: participants who signed informed consent form, had an evaluable EQ-5D questionnaire at baseline and at least one evaluable assessment post baseline and received at least part of one dose of study treatment (either Aflibercept or FOLFIRI).Here, n = number of participants with available data at specified time-points.</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept + FOLFIRI (Irinotecan, 5-FU &amp; Leucovorin)</title>
            <description>Aflibercept 4 mg/kg IV infusion over 60 minutes followed by Irinotecan 180 mg/m^2 IV infusion over 90 minutes and Leucovorin 400 mg/m^2 IV infusion over 120 minutes at the same time followed by 5-FU 400 mg/m^2 IV bolus over 2-4 minutes followed by 5-FU 2400 mg/m^2 continuous IV infusion over 46 hours on Day 1 of each cycle (1 Cycle = 2 weeks), until DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in HRQL European-Quality of Life-5 Dimension Instrument-3 Levels (EQ-5D-3L) Index Score</title>
          <description>EQ-5D was a standardized HRQL questionnaire consisting of EQ-5D descriptive system and Visual Analogue Scale (VAS). EQ-5D descriptive system comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression measured on 3 levels (no problem, some problems &amp; severe problems) within a particular EQ-5D dimension. 5 dimensional 3-level system was converted into single index utility score. Possible values for single index utility score ranged from -0.594 (severe problems in all dimensions) to 1.0 (no problem in all dimensions) on scale where 1 represented best possible health state.</description>
          <population>EQ-5D analysis population: participants who signed informed consent form, had an evaluable EQ-5D questionnaire at baseline and at least one evaluable assessment post baseline and received at least part of one dose of study treatment (either Aflibercept or FOLFIRI).Here, n = number of participants with available data at specified time-points.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="148"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (n=148)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.78" spread="0.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 3 (n=127)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.04" spread="0.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 5 (n=96)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.08" spread="0.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 7 (n=72)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.05" spread="0.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 9 (n=49)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.09" spread="0.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 11 (n=43)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.06" spread="0.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 13 (n=24)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.09" spread="0.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 15 (n=25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.10" spread="0.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 17 (n=14)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.03" spread="0.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 19 (n=12)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.10" spread="0.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 21 (n=10)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.03" spread="0.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 23 (n=6)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.08" spread="0.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 25 (n=3)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.04" spread="0.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 27 (n=3)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.09" spread="0.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 29 (n=2)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.18" spread="0.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 31 (n=1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="NA">As only one participant was analyzed at cycle 31, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 37 (n=1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.15" spread="NA">As only one participant was analyzed at cycle 37, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 39 (n=1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="NA">As only one participant was analyzed at cycle 39, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 41 (n=1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="NA">As only one participant was analyzed at cycle 41, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 43 (n=1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="NA">As only one participant was analyzed at cycle 43, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At Cycle 45 (n=1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="NA">As only one participant was analyzed at cycle 45, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At end of study treatment (n=71)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.20" spread="0.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in HRQL EQ-5D-3L VAS Score</title>
        <description>EQ-5D VAS was used to record a participant's rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 = worst imaginable health state and 100 = best imaginable health state. Baseline corresponded to last evaluable assessment before treatment administration.</description>
        <time_frame>Pre-dose at Baseline, Day 1 of every odd cycle; and at end of treatment (30 days after last study treatment) (maximum exposure: 99 weeks)</time_frame>
        <population>EQ-5D analysis population: participants who signed informed consent form, had an evaluable EQ-5D questionnaire at baseline and at least one evaluable assessment post baseline and received at least part of one dose of study treatment (either Aflibercept or FOLFIRI).Here, n = number of participants with available data at specified time-points.</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept + FOLFIRI (Irinotecan, 5-FU &amp; Leucovorin)</title>
            <description>Aflibercept 4 mg/kg IV infusion over 60 minutes followed by Irinotecan 180 mg/m^2 IV infusion over 90 minutes and Leucovorin 400 mg/m^2 IV infusion over 120 minutes at the same time followed by 5-FU 400 mg/m^2 IV bolus over 2-4 minutes followed by 5-FU 2400 mg/m^2 continuous IV infusion over 46 hours on Day 1 of each cycle (1 Cycle = 2 weeks), until DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in HRQL EQ-5D-3L VAS Score</title>
          <description>EQ-5D VAS was used to record a participant's rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 = worst imaginable health state and 100 = best imaginable health state. Baseline corresponded to last evaluable assessment before treatment administration.</description>
          <population>EQ-5D analysis population: participants who signed informed consent form, had an evaluable EQ-5D questionnaire at baseline and at least one evaluable assessment post baseline and received at least part of one dose of study treatment (either Aflibercept or FOLFIRI).Here, n = number of participants with available data at specified time-points.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="148"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (n=125)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="69.48" spread="19.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At cycle 3 (n=94)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.23" spread="17.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At cycle 5 (n=76)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.62" spread="17.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At cycle 7 (n=57)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.79" spread="14.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At cycle 9 (n=38)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.55" spread="16.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At cycle 11 (n=36)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.67" spread="16.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At cycle 13 (n=22)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.95" spread="17.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At cycle 15 (n=22)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-12.41" spread="19.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At cycle 17 (n=13)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.31" spread="17.44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At cycle 19 (n=10)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.70" spread="18.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At cycle 21 (n=8)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.13" spread="19.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At cycle 23 (n=5)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.80" spread="10.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At cycle 25 (n=2)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-13.00" spread="4.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At cycle 27 (n=3)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.67" spread="9.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At cycle 29 (n=2)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-17.50" spread="3.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At cycle 31 (n=1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.00" spread="NA">As only one participant was analyzed at cycle 31, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At cycle 37 (n=1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.00" spread="NA">As only one participant was analyzed at cycle 37, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At cycle 39 (n=1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.00" spread="NA">As only one participant was analyzed at cycle 39, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At cycle 41 (n=1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.00" spread="NA">As only one participant was analyzed at cycle 41, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At cycle 43 (n=1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.00" spread="NA">As only one participant was analyzed at cycle 43, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At cycle 45 (n=1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.00" spread="NA">As only one participant was analyzed at cycle 45, standard deviation could not be calculated.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At end of study treatment (n=55)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-13.05" spread="20.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 723) regardless of seriousness or relationship to investigational product.</time_frame>
      <desc>Reported AEs and deaths are treatment-emergent that is AEs that developed/worsened and deaths that occurred during 'on-treatment period' (from the first dose of treatment to 30 days after the last dose of treatment [either aflibercept or FOLFIRI]).</desc>
      <group_list>
        <group group_id="E1">
          <title>Aflibercept + FOLFIRI(Irinotecan, 5-Fluorouracil &amp; Leucovorin)</title>
          <description>Aflibercept 4 mg/kg IV infusion over 60 minutes followed by Irinotecan 180 mg/m^2 IV infusion over 90 minutes and Leucovorin 400 mg/m^2 IV infusion over 120 minutes at the same time followed by 5-FU 400 mg/m^2 IV bolus over 2-4 minutes followed by 5-FU 2400 mg/m^2 continuous IV infusion over 46 hours on Day 1 of each cycle (1 Cycle = 2 weeks), until DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment (maximum exposure: Week 99).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 18.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="71" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>ANAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>FEBRILE NEUTROPENIA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>PANCYTOPENIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>VITREOUS HAEMORRHAGE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>ABDOMINAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>ANAL FISTULA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>DIARRHOEA</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>GASTROINTESTINAL FISTULA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>GASTROINTESTINAL HAEMORRHAGE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>INTESTINAL OBSTRUCTION</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>NAUSEA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>PANCREATITIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>RECTAL HAEMORRHAGE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>RECTOURETHRAL FISTULA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>SMALL INTESTINAL PERFORATION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>STOMATITIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>SUBILEUS</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>TOOTH LOSS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>VOMITING</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>ASTHENIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>DISEASE PROGRESSION</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>FATIGUE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>GENERAL PHYSICAL HEALTH DETERIORATION</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>INFLUENZA LIKE ILLNESS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>PYREXIA</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>HEPATIC FAILURE</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>ABDOMINAL WALL ABSCESS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>DEVICE RELATED INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>DEVICE RELATED SEPSIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>ESCHERICHIA INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>LUNG INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>PELVIC ABSCESS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>SEPSIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>SEPTIC SHOCK</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>TOOTH INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>HEAD INJURY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>BLOOD ALKALINE PHOSPHATASE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>LAPAROSCOPY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>DECREASED APPETITE</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>DEHYDRATION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>HYPERGLYCAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>HYPOKALAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>BONE PAIN</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>INFECTED NEOPLASM</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>METASTASES TO CENTRAL NERVOUS SYSTEM</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>METASTATIC PAIN</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>CEREBELLAR ISCHAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>CEREBROVASCULAR ACCIDENT</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>DIZZINESS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>HEADACHE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>NEUROPATHY PERIPHERAL</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>CONFUSIONAL STATE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>DEPRESSION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>RENAL COLIC</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>RENAL FAILURE</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>URINARY RETENTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>PRIAPISM</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>DYSPNOEA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>EPISTAXIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>PLEURAL EFFUSION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>PNEUMOTHORAX</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>PULMONARY EMBOLISM</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>PULMONARY OEDEMA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>HEPATECTOMY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>INTRAPERITONEAL HYPERTHERMIC CHEMOTHERAPY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>PHLEBITIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>THROMBOSIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>VARICOSE ULCERATION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 18.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="172" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>NEUTROPENIA</sub_title>
                <counts group_id="E1" subjects_affected="39" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>ABDOMINAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="36" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>ABDOMINAL PAIN UPPER</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>CONSTIPATION</sub_title>
                <counts group_id="E1" subjects_affected="39" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>DIARRHOEA</sub_title>
                <counts group_id="E1" subjects_affected="121" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>GASTROOESOPHAGEAL REFLUX DISEASE</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>NAUSEA</sub_title>
                <counts group_id="E1" subjects_affected="86" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>PROCTALGIA</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>RECTAL HAEMORRHAGE</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>STOMATITIS</sub_title>
                <counts group_id="E1" subjects_affected="83" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>VOMITING</sub_title>
                <counts group_id="E1" subjects_affected="47" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>ASTHENIA</sub_title>
                <counts group_id="E1" subjects_affected="98" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>FATIGUE</sub_title>
                <counts group_id="E1" subjects_affected="33" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>PYREXIA</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>WEIGHT DECREASED</sub_title>
                <counts group_id="E1" subjects_affected="68" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>DECREASED APPETITE</sub_title>
                <counts group_id="E1" subjects_affected="59" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>ARTHRALGIA</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>BACK PAIN</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>MYALGIA</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>DYSGEUSIA</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>HEADACHE</sub_title>
                <counts group_id="E1" subjects_affected="32" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>NEUROPATHY PERIPHERAL</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>PARAESTHESIA</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>PROTEINURIA</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>DYSPHONIA</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>DYSPNOEA</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>EPISTAXIS</sub_title>
                <counts group_id="E1" subjects_affected="43" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>ALOPECIA</sub_title>
                <counts group_id="E1" subjects_affected="36" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>HYPERTENSION</sub_title>
                <counts group_id="E1" subjects_affected="74" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Trial Transparency Team</name_or_title>
      <organization>Sanofi</organization>
      <email>Contact-US@sanofi.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01670721
org study id: AFLIBL06266
secondary id: 2012-000048-89
secondary id: U1111-1128-9325
nct id: NCT01670721
lead sponsor: 
collaborator: 
has dmc: No
Primary Objective:

      To evaluate the safety of aflibercept in participants with mCRC treated with
      irinotecan/5-Fluorouracil (5-FU) combination (FOLFIRI) after failure of an oxaliplatin-based
      regimen (participants similar to those evaluated in the VELOUR trial [EFC10262, NCT00561470])
      according to side effects prevention and management guidelines.

      Secondary Objective:

      To document the Health-Related Quality of Life (HRQL) of aflibercept in this participant
      population.
Each participant was treated until disease progression (DP), unacceptable toxicity, death,
      Investigator's decision or participant's refusal for further treatment (whichever come
      first). Participants were followed-up during treatment and for at least 30 days after its
      last study treatment (either Aflibercept or FOLFIRI) administration, up to a maximum of 6
      months.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants With Adverse Events (AEs)
time frame: Baseline upto 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure:723 days)
description: Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period. On-treatment period was defined as the time from the first dose of treatment to 30 days after the last dose of treatment (either Aflibercept or FOLFIRI). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.
measure: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment for Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
time frame: Pre-dose at Baseline, Day 1 of every odd cycle; and at end of treatment (30 days after last study treatment) (maximum exposure: 99 weeks)
description: EORTC-QLQ-C30 is a cancer-specific instrument with 30 questions for evaluation of new chemotherapy and provides an assessment of participant reported outcome dimensions. First 28 questions used 4-point scale (1=not at all,2=a little,3=quite a bit,4=very much) for evaluating 5 functional scales (physical,role,emotional,cognitive,social), 3 symptom scales (fatigue,nausea/vomiting,pain) & other single items. For each item,high score represented high level of symptomatology/problem. Last 2 questions represented participant's assessment of overall health & quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 observed values and change from baseline for global health status (scoring of questions 29 & 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28). Answers were converted into grading scale, with values between 0 and 100. A high score represented a favorable outcome with a best quality of life for participant.
measure: Change From Baseline in HRQL European-Quality of Life-5 Dimension Instrument-3 Levels (EQ-5D-3L) Index Score
time frame: Pre-dose at Baseline, Day 1 of every odd cycle; and at end of treatment (30 days after last study treatment) (maximum exposure: 99 weeks)
description: EQ-5D was a standardized HRQL questionnaire consisting of EQ-5D descriptive system and Visual Analogue Scale (VAS). EQ-5D descriptive system comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression measured on 3 levels (no problem, some problems & severe problems) within a particular EQ-5D dimension. 5 dimensional 3-level system was converted into single index utility score. Possible values for single index utility score ranged from -0.594 (severe problems in all dimensions) to 1.0 (no problem in all dimensions) on scale where 1 represented best possible health state.
measure: Change From Baseline in HRQL EQ-5D-3L VAS Score
time frame: Pre-dose at Baseline, Day 1 of every odd cycle; and at end of treatment (30 days after last study treatment) (maximum exposure: 99 weeks)
description: EQ-5D VAS was used to record a participant's rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 = worst imaginable health state and 100 = best imaginable health state. Baseline corresponded to last evaluable assessment before treatment administration.
arm group label: Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
arm group type: Experimental
description: Aflibercept 4 mg/kg intravenous (IV) infusion over 60 minutes followed by Irinotecan 180 mg/m^2 IV infusion over 90 minutes and Leucovorin 400 mg/m^2 IV infusion over 120 minutes at the same time followed by 5-FU 400 mg/m^2 IV bolus over 2-4 minutes followed by 5-FU 2400 mg/m^2 continuous IV infusion over 46 hours on Day 1 of each cycle (1 Cycle = 2 weeks), until DP, unacceptable toxicity, death, Investigator's decision or participant's refusal of further treatment.
intervention type: Drug
intervention name: AFLIBERCEPT
description: Pharmaceutical form:Concentrate for solution for infusion; Route of administration: Intravenous
arm group label: Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
other name: AVE0005
intervention type: Drug
intervention name: Irinotecan
description: Pharmaceutical form:Concentrate for solution for infusion; Route of administration: Intravenous
arm group label: Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
intervention type: Drug
intervention name: Fluorouracil
description: Pharmaceutical form:Concentrate for solution for infusion; Route of administration: Intravenous
arm group label: Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
intervention type: Drug
intervention name: Leucovorin
description: Pharmaceutical form:Concentrate for solution for infusion; Route of administration: Intravenous
arm group label: Aflibercept + FOLFIRI (Irinotecan, 5-FU & Leucovorin)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Sciences & Operations
role: Study Director
affiliation: Sanofi
facility: 
country: France
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Leucovorin
mesh term: Fluorouracil
mesh term: Irinotecan
mesh term: Aflibercept
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 