<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/NCT01669720</url>
  </required_header>
  <id_info>
    <org_study_id>BrUOG C261</org_study_id>
    <nct_id>NCT01669720</nct_id>
  </id_info>
  <brief_title>Adjuvant Aflibercept for Metastatic Colorectal Cancer</brief_title>
  <acronym>C261</acronym>
  <official_title>BrUOG C261:Single Agent Adjuvant Aflibercept for Patients With Resected or Ablated Metastatic Colorectal Cancer: A Randomized Phase II Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brown University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Rhode Island Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Miriam Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Lifespan</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of California, San Diego</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Montefiore Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Florida</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Brown University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of this study is to evaluate if aflibercept can reduce the chance that&#xD;
      metastatic (spread of) colorectal cancer can grow back after finishing standard treatment.&#xD;
      The study will also look at the side effects of aflibercept and the effect on quality of&#xD;
      life.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There are over 1.2 million new cases of colorectal cancer and 600,000 deaths worldwide. The&#xD;
      liver is the dominant site of metastases. Approximately 20-25% of patients with advanced&#xD;
      colorectal cancer will be candidates for resection/ablation of all sites of metastatic&#xD;
      disease.1 Unfortunately, despite resection/ablation of all metastatic sites only about 20% of&#xD;
      these patients are ultimately cured.1 An effective adjuvant agent would prevent tumor&#xD;
      recurrence.&#xD;
&#xD;
      Aflibercept and bevacizumab are effective when combined with FOLFIRI for metastatic colon&#xD;
      cancer. Neither has been tested in a randomized study in the adjuvant setting for patients&#xD;
      with resected metastatic disease. Since aflibercept more effectively inhibits all forms of&#xD;
      VEGF including VEGF-A, VEGF-B and PIGF, in striking contrast to bevacizumab which inhibits&#xD;
      only VEGF-A, aflibercept likely will be more effective than bevacizumab as a single agent in&#xD;
      the adjuvant metastatic setting. Therefore, we propose a randomized study of adjuvant&#xD;
      aflibercept for patients metastatic colorectal cancer who have received 10-12 cycles of&#xD;
      perioperative FOLFOX and have had had a complete response to all sites of metastases after&#xD;
      chemotherapy and local modalities such as surgical resection or ablation. SBRT may also be&#xD;
      used to produce a complete response in a metastatic site not easily amenable to surgery or&#xD;
      ablation. Only patients with very high risk of recurrence, defined as 3 or more metastatic&#xD;
      sites, will be included in this study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Lack of efficacy and enrollment&#xD;
  </why_stopped>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">January 2016</completion_date>
  <primary_completion_date type="Actual">December 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Patients Who Progressed</measure>
    <time_frame>Every 3 months until disease progression (for up to 2 years).</time_frame>
    <description>Disease free survival in patients with advanced colorectal cancer who have undergone resection/ablation of all metastatic sites.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Experienced a Toxicity Profile of Adjuvant Ziv-aflibercept, up to 2-years of Duration, for Patients Who Previously Received Systemic Perioperative Therapy (Regimen) and Surgical Resection/Ablation.</measure>
    <time_frame>Throughout study treatment until 30 days post off study, approximately 2 years</time_frame>
    <description>Toxicity defined by CTCAE Version 4.0 toxicities</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Metastatic Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>Aflibercept</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be randomized 2:1, to receive Aflibercept,4mg/kg IV q2weeks until progression for a maximum of 2 years</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Observation</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients will be randomized 2:1 to receive Aflibercept. Patients who are randomized to observation will be followed per the study table, but will receive no intervention.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aflibercept</intervention_name>
    <description>Aflibercept: 4mg/kg IV q2weeks until progression for a maximum of 2 years</description>
    <arm_group_label>Aflibercept</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        3.1.1 First-line treatment of metastatic colorectal cancer with 3 or more metastases&#xD;
        3.1.2At least 10 cycles of combination therapy with an oxaliplatin or irinotecan based&#xD;
        regimen per institutional preference (patients may receive 6 cycles, go to surgery, then&#xD;
        complete 4 cycles, they may complete all 10 (or more) prior to surgery, or receive any&#xD;
        combination as long as they receive at least 10 cycles. ) 3.1.3 Resection or ablation of&#xD;
        all metastatic sites that have not achieved complete response with perioperative therapy&#xD;
        (regimen). The sequencing of resection, ablation, and 10-12 cycles of combination therapy&#xD;
        (regimen) with an oxaliplatin or irinotecan based regimen may be performed according to&#xD;
        standard institutional procedure.&#xD;
&#xD;
        3.1.4 Patients achieving a complete response in a metastatic site by stereotactic body&#xD;
        radiation are eligible if the site was not easily accessible by surgery or ablation and a&#xD;
        complete response was achieved.&#xD;
&#xD;
        3.1.5 No severe, uncontrolled concurrent illness that would interfere with protocol&#xD;
        therapy.&#xD;
&#xD;
        3.1.6 No known CNS disease 3.1.7 ECOG Performance Status 0-2 3.1.8 No chemotherapy or&#xD;
        radiation therapy within last 3 weeks 3.1.9 For patients who had 3 months of perioperative&#xD;
        therapy (regimen), then surgery, then 3 months of therapy (regimen), patients must be off&#xD;
        therapy for no more than 8 weeks prior to randomization. For patients who had all their&#xD;
        therapy and then surgery, they must be no more than 8 weeks from surgery prior to&#xD;
        randomization.&#xD;
&#xD;
        3.1.10 No concurrent anticancer therapy. 3.1.11 Absolute neutrophil count ≥ 1,500/uL, Hgb &gt;&#xD;
        9.0 g/dl, platelet ≥ 100,000/uL.&#xD;
&#xD;
        3.1.12 Total bilirubin ≤ 1.5x upper limit of normal (ULN) and AST or ALT ≤ 5x ULN; 3.1.13&#xD;
        Creatinine &lt; 1.5 x ULN 3.1.14 Life expectancy of at least 12 weeks. 3.1.15 Age ≥ 18 years&#xD;
        3.1.16 Women of childbearing potential must have a negative pregnancy test. 3.1.17 Men and&#xD;
        women of childbearing potential must be willing to consent to using effective contraception&#xD;
        while on treatment and for at least 3 months thereafter.&#xD;
&#xD;
        3.1.18 Voluntary written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        3.2.1 Residual metastatic disease after resection/ablation 3.2.2 Clinically significant&#xD;
        cardiac disease (e.g., uncontrolled hypertension [blood pressure of &gt;160/90 mmHg on&#xD;
        medication], history of myocardial infarction within 6 months,), New York Heart Association&#xD;
        (NYHA) Class II or greater congestive heart failure within 6 months, unstable arrhythmia.&#xD;
        Patients with an atrial arrhythmia must have this condition well controlled on stable&#xD;
        medication. Patients with current or recent (within 6 months) unstable angina are also not&#xD;
        eligible. Documentation of cardiac medical history to be provided.&#xD;
&#xD;
        3.2.3 Significant bleeding diathesis or coagulopathy 3.2.4 History of cerebral aneurysms or&#xD;
        cerebral arteriovenous malformations. 3.2.5 Patients with recent (within 12 months)&#xD;
        arterial thromboembolic events, including transient ischemic attack (TIA), cerebrovascular&#xD;
        accident (CVA), or clinically significant peripheral artery disease should also be&#xD;
        excluded.&#xD;
&#xD;
        3.2.6 Patients with a history of a gastrointestinal fistula or perforation. 3.2.7 Women who&#xD;
        are breast-feeding. 3.2.8 Patients who have undergone major surgery, chemotherapy, or&#xD;
        radiotherapy within the last 3 weeks.&#xD;
&#xD;
        3.2.9 Patients on concurrent anticancer therapy.&#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>Howard Safran, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Brown University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rhode Island Hospital (East Greenwich and Newport)</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Miriam Hospital</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>August 7, 2012</study_first_submitted>
  <study_first_submitted_qc>August 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 2012</study_first_posted>
  <results_first_submitted>January 8, 2016</results_first_submitted>
  <results_first_submitted_qc>February 11, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">March 10, 2016</results_first_posted>
  <last_update_submitted>February 13, 2020</last_update_submitted>
  <last_update_submitted_qc>February 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 17, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Brown University</investigator_affiliation>
    <investigator_full_name>howard safran</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Metastatic</keyword>
  <keyword>Colorectal</keyword>
  <keyword>Colorectal Cancer</keyword>
  <keyword>Resected or Ablated Metastatic Colorectal Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aflibercept</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Aflibercept</title>
          <description>Patients will be randomized 2:1, to receive Aflibercept,4mg/kg IV q2weeks until progression for a maximum of 2 years&#xD;
Aflibercept: Aflibercept: 4mg/kg IV q2weeks until progression for a maximum of 2 years</description>
        </group>
        <group group_id="P2">
          <title>Observation</title>
          <description>Patients will be randomized 2:1 to receive Aflibercept. Patients who are randomized to observation will be followed per the study table, but will receive no intervention.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Aflibercept</title>
          <description>Patients will be randomized 2:1, to receive Aflibercept,4mg/kg IV q2weeks until progression for a maximum of 2 years&#xD;
Aflibercept: Aflibercept: 4mg/kg IV q2weeks until progression for a maximum of 2 years</description>
        </group>
        <group group_id="B2">
          <title>Observation</title>
          <description>Patients will be randomized 2:1 to receive Aflibercept. Patients who are randomized to observation will be followed per the study table, but will receive no intervention.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="7"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="10"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="53.5" lower_limit="46" upper_limit="61"/>
                    <measurement group_id="B2" value="57" lower_limit="44" upper_limit="75"/>
                    <measurement group_id="B3" value="54.6" lower_limit="44" upper_limit="75"/>
                  </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="5"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Patients Who Progressed</title>
        <description>Disease free survival in patients with advanced colorectal cancer who have undergone resection/ablation of all metastatic sites.</description>
        <time_frame>Every 3 months until disease progression (for up to 2 years).</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept</title>
            <description>Patients will be randomized 2:1, to receive Aflibercept,4mg/kg IV q2weeks until progression for a maximum of 2 years&#xD;
Aflibercept: Aflibercept: 4mg/kg IV q2weeks until progression for a maximum of 2 years</description>
          </group>
          <group group_id="O2">
            <title>Observation</title>
            <description>Patients will be randomized 2:1 to receive Aflibercept. Patients who are randomized to observation will be followed per the study table, but will receive no intervention.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients Who Progressed</title>
          <description>Disease free survival in patients with advanced colorectal cancer who have undergone resection/ablation of all metastatic sites.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Experienced a Toxicity Profile of Adjuvant Ziv-aflibercept, up to 2-years of Duration, for Patients Who Previously Received Systemic Perioperative Therapy (Regimen) and Surgical Resection/Ablation.</title>
        <description>Toxicity defined by CTCAE Version 4.0 toxicities</description>
        <time_frame>Throughout study treatment until 30 days post off study, approximately 2 years</time_frame>
        <population>Data table reflects total number of patients who experienced a toxicity on study.</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept</title>
            <description>Patients will be randomized 2:1, to receive Aflibercept,4mg/kg IV q2weeks until progression for a maximum of 2 years&#xD;
Aflibercept: Aflibercept: 4mg/kg IV q2weeks until progression for a maximum of 2 years</description>
          </group>
          <group group_id="O2">
            <title>Observation</title>
            <description>Patients will be randomized 2:1 to receive Aflibercept. Patients who are randomized to observation will be followed per the study table, but will receive no intervention.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Experienced a Toxicity Profile of Adjuvant Ziv-aflibercept, up to 2-years of Duration, for Patients Who Previously Received Systemic Perioperative Therapy (Regimen) and Surgical Resection/Ablation.</title>
          <description>Toxicity defined by CTCAE Version 4.0 toxicities</description>
          <population>Data table reflects total number of patients who experienced a toxicity on study.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Every 2 weeks until 30 days post last dose of drug</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Aflibercept</title>
          <description>Patients will be randomized 2:1, to receive Aflibercept,4mg/kg IV q2weeks until progression for a maximum of 2 years&#xD;
Aflibercept: Aflibercept: 4mg/kg IV q2weeks until progression for a maximum of 2 years</description>
        </group>
        <group group_id="E2">
          <title>Observation</title>
          <description>Patients will be randomized 2:1 to receive Aflibercept. Patients who are randomized to observation will be followed per the study table, but will receive no intervention.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="6" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>HTN</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Bronchial infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>UTI</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>ALK</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Glu</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>proteinuria</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>PLT</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>AST</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>ALT</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>bruising</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>akathisia/restlessness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>rash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>fatigue</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>lymph</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Sodium</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Edema- localized</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>pain-hip/leg, mouth, abd</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>mucositis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>creatinine</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>WBC</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>neuropathy</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>arthralgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>weight gain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>vision-blurry</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>increased hemoglobin</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>insomnia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>anorexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Howard Safran, MD</name_or_title>
      <organization>Brown University Oncology Research Group (BrUOG)</organization>
      <phone>4018633000</phone>
      <email>kayla_rosati@brown.edu</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/NCT01669720
org study id: BrUOG C261
nct id: NCT01669720
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The main purpose of this study is to evaluate if aflibercept can reduce the chance that
      metastatic (spread of) colorectal cancer can grow back after finishing standard treatment.
      The study will also look at the side effects of aflibercept and the effect on quality of
      life.
There are over 1.2 million new cases of colorectal cancer and 600,000 deaths worldwide. The
      liver is the dominant site of metastases. Approximately 20-25% of patients with advanced
      colorectal cancer will be candidates for resection/ablation of all sites of metastatic
      disease.1 Unfortunately, despite resection/ablation of all metastatic sites only about 20% of
      these patients are ultimately cured.1 An effective adjuvant agent would prevent tumor
      recurrence.

      Aflibercept and bevacizumab are effective when combined with FOLFIRI for metastatic colon
      cancer. Neither has been tested in a randomized study in the adjuvant setting for patients
      with resected metastatic disease. Since aflibercept more effectively inhibits all forms of
      VEGF including VEGF-A, VEGF-B and PIGF, in striking contrast to bevacizumab which inhibits
      only VEGF-A, aflibercept likely will be more effective than bevacizumab as a single agent in
      the adjuvant metastatic setting. Therefore, we propose a randomized study of adjuvant
      aflibercept for patients metastatic colorectal cancer who have received 10-12 cycles of
      perioperative FOLFOX and have had had a complete response to all sites of metastases after
      chemotherapy and local modalities such as surgical resection or ablation. SBRT may also be
      used to produce a complete response in a metastatic site not easily amenable to surgery or
      ablation. Only patients with very high risk of recurrence, defined as 3 or more metastatic
      sites, will be included in this study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Patients Who Progressed
time frame: Every 3 months until disease progression (for up to 2 years).
description: Disease free survival in patients with advanced colorectal cancer who have undergone resection/ablation of all metastatic sites.
measure: Number of Participants Who Experienced a Toxicity Profile of Adjuvant Ziv-aflibercept, up to 2-years of Duration, for Patients Who Previously Received Systemic Perioperative Therapy (Regimen) and Surgical Resection/Ablation.
time frame: Throughout study treatment until 30 days post off study, approximately 2 years
description: Toxicity defined by CTCAE Version 4.0 toxicities
arm group label: Aflibercept
arm group type: Experimental
description: Patients will be randomized 2:1, to receive Aflibercept,4mg/kg IV q2weeks until progression for a maximum of 2 years
arm group label: Observation
arm group type: No Intervention
description: Patients will be randomized 2:1 to receive Aflibercept. Patients who are randomized to observation will be followed per the study table, but will receive no intervention.
intervention type: Drug
intervention name: Aflibercept
description: Aflibercept: 4mg/kg IV q2weeks until progression for a maximum of 2 years
arm group label: Aflibercept
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Howard Safran, MD
role: Principal Investigator
affiliation: Brown University
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Brown University
investigator full name: howard safran
investigator title: Principal Investigator
mesh term: Colorectal Neoplasms
mesh term: Aflibercept
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 