<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/NCT01695772</url>
  </required_header>
  <id_info>
    <org_study_id>ML28419</org_study_id>
    <nct_id>NCT01695772</nct_id>
  </id_info>
  <brief_title>A Study of Bevacizumab Plus 5-Flurouracil (5-FU) Based Doublet Chemotherapy as Neoadjuvant Therapy for Participants With Previously Untreated Unresectable Liver-Only Metastases From Colorectal Cancer</brief_title>
  <official_title>A Multi-Center, Single-Arm, Pilot Study of 5-FU Based Doublet Chemotherapy Plus Bevacizumab as Neoadjuvant Therapy for Patients With Previously Untreated Unresectable Liver-Only Metastases From Colorectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This open-label, single arm, multicenter study evaluated the resection rate in participants&#xD;
      with colorectal cancer and previously untreated unresectable liver-only metastases after&#xD;
      adding bevacizumab to 5-FU based doublet chemotherapy in the neoadjuvant setting.&#xD;
      Participants receive standard 5-FU based chemotherapy plus Avastin bevacizumab 5 milligrams&#xD;
      per kilogram (mg/kg) every 2 weeks for a maximum of 12 cycles combined pre- and&#xD;
      postoperatively, unless they experienced progressive disease or unacceptable toxicity.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 16, 2012</start_date>
  <completion_date type="Actual">May 12, 2016</completion_date>
  <primary_completion_date type="Actual">April 4, 2015</primary_completion_date>
  <phase>Phase 4</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 Achieving Complete Resection (R0 Resection)</measure>
    <time_frame>At time of surgery (up to 28 weeks), 48 hours post-surgery and 4 and 12 weeks after surgery (up to 40 weeks)</time_frame>
    <description>R0 resection was defined as complete resection confirmed by pathology after pre-operative chemotherapy plus bevacizumab. Participants with R0 resections based on assessments performed at time of surgery, 48 hours post-surgery and 4 and 12 weeks after surgery were reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving Incomplete Tumor Resection (R1 Resection)</measure>
    <time_frame>At time of surgery (up to 28 weeks), 48 hours post-surgery and 4 and 12 weeks after surgery (up to 40 weeks)</time_frame>
    <description>R1 resection was defined as achievement of incomplete tumor resection with microscopic involvement of a margin after pre-operative chemotherapy plus bevacizumab, as confirmed by pathology. Participants with R1 resections based on assessments performed at time of surgery, 48 hours post-surgery and 4 and 12 weeks after surgery were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving Objective Response</measure>
    <time_frame>Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)</time_frame>
    <description>Objective response rate was defined as the percentage of participants who achieved either Partial Response (PR) or Complete Response (CR) per Response Evaluation Criteria In Solid Tumors (RECIST) version (v) 1.1. This is defined as the best response recorded from the start of trial treatment until disease progression (or death). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than [&lt;] 10 mm). No new lesions. PR was defined as greater than or equal to [≥] 30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Disease Progression or Relapse or Death</measure>
    <time_frame>Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)</time_frame>
    <description>According to RECIST v1.1 Progressive Disease is defined as a 20 % or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)</time_frame>
    <description>Progressive Disease is defined as a 20% or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions. PFS was defined as the time from initiation of study treatment to disease progression, as determined by the investigator using RECIST v1.1 criterion, or relapse after resection of liver metastases or death from any cause. Kaplan-Meier curves were used to display PFS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Probability (PP) of Being Alive and Progression Free at Months 3, 6, 9, 12, 15, and 18</measure>
    <time_frame>Months 3, 6, 9, 12, 15, and 18</time_frame>
    <description>Progressive Disease is defined as a 20% or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions. PFS was defined as the time from initiation of study treatment to disease progression, as determined by the investigator using RECIST v1.1 criterion, or relapse after resection of liver metastases or death from any cause. The probability was estimated by Kaplan Meier curve analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Disease Relapse or Death</measure>
    <time_frame>Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Free Survival (DFS)</measure>
    <time_frame>Complete resection date up to disease relapse or death until data cutoff on 12 May 2016 (up to approximately 3.5 years)</time_frame>
    <description>Disease Free Survival (DFS) was defined as the time from complete resection of liver metastases to disease relapse or death, for participants who achieve complete resection after pre-operative treatment with standard 5-FU based doublet regimen plus bevacizumab.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Probability Of Being Alive and Disease Free at Months 3, 6, 9, and 12</measure>
    <time_frame>Months 3, 6, 9, and 12</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>Bevacizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5-FU based doublet chemotherapy</intervention_name>
    <description>Standard 5-FU based doublet chemotherapy. Protocol did not specify any particular chemotherapy regimen. The choice of 5-FU based doublet chemotherapy was as per standard of practice and the dosage of 5-FU based doublet chemotherapy was as per product labels.</description>
    <arm_group_label>Bevacizumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>bevacizumab</intervention_name>
    <description>5 mg/kg every 2 weeks, up to 12 cycles pre- and postoperatively</description>
    <arm_group_label>Bevacizumab</arm_group_label>
    <other_name>Avastin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult Chinese participants, 18-75 years of age&#xD;
&#xD;
          -  Histologically confirmed adenocarcinoma in colon or rectum with primary lesion&#xD;
             surgically removed&#xD;
&#xD;
          -  Previously untreated unresectable liver-only metastases&#xD;
&#xD;
          -  Liver lesions determined to be unresectable by multidisciplinary team (MDT, consisting&#xD;
             of experienced hepatic surgeons, medical oncologist and radiologist).&#xD;
&#xD;
          -  No previous treatment against liver metastases, including chemotherapy, surgery,&#xD;
             radiotherapy, Transarterial chemoembolisation therapy (TACE) and target therapy&#xD;
&#xD;
          -  Adequate hematological, renal and hepatic function&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1&#xD;
&#xD;
          -  Life expectancy greater than (&gt;) 3 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The relapse has occurred within 6 months of completion of the adjuvant treatment&#xD;
&#xD;
          -  Expected impossible to achieve complete resection (R0 resection) and/or gain 30%&#xD;
             residual liver volume even with responsive neoadjuvant therapy&#xD;
&#xD;
          -  Participant cannot tolerate the surgery&#xD;
&#xD;
          -  Other malignancies in the past 5 years, except for curatively treated basal cell&#xD;
             carcinoma of the skin and/or in situ carcinoma of the cervix&#xD;
&#xD;
          -  Any extrahepatic metastases and/or recurrence of the primary tumor&#xD;
&#xD;
          -  Any residual toxicity from previous chemotherapy (except alopecia) of National Cancer&#xD;
             Institute Common Toxicity Criteria (NCI CTC) v.4.0 grade 2&#xD;
&#xD;
          -  Hypertension crisis or encephalopathy&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Clinically significant cardiovascular disease&#xD;
&#xD;
          -  Evidence of bleeding diathesis or coagulopathy&#xD;
&#xD;
          -  Current or recent (within 10 days of study drug initiation) use of full dose of&#xD;
             aspirin, clopidrogel or warfarin&#xD;
&#xD;
          -  History or evidence of Central Nervous System (CNS) disease (for example, primary&#xD;
             brain tumor, seizures not controlled with standard medical therapy, any brain&#xD;
             metastases, or history of stroke)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Beijing Cancer Hospital</name>
      <address>
        <city>Beijing</city>
        <zip>100142</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sun Yet-sen University Cancer Center</name>
      <address>
        <city>Guangzhou</city>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Second Affiliated Hospital of Zhejiang University College</name>
      <address>
        <city>Hangzhou</city>
        <zip>310009</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The 2nd Affiliated Hospital of Harbin Medical University</name>
      <address>
        <city>Harbin</city>
        <zip>150001</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zhongshan Hospital Fudan University</name>
      <address>
        <city>Shanghai</city>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Liaoning cancer Hospital &amp; Institute</name>
      <address>
        <city>Shenyang</city>
        <zip>110042</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Xiehe Hospital, Tongji Medical College Huazhong University of Science &amp; Technology</name>
      <address>
        <city>Wuhan</city>
        <zip>430022</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>September 27, 2012</study_first_submitted>
  <study_first_submitted_qc>September 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 28, 2012</study_first_posted>
  <results_first_submitted>June 17, 2016</results_first_submitted>
  <results_first_submitted_qc>June 17, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">July 28, 2016</results_first_posted>
  <last_update_submitted>May 11, 2017</last_update_submitted>
  <last_update_submitted_qc>May 11, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2017</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>Bevacizumab</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Protocol did not specify any particular 5-Flurouracil (5-FU) based doublet chemotherapy regimen. The choice of 5-FU based doublet chemotherapy was as per standard of practice and the dosage of 5-FU based doublet chemotherapy was as per product labels.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Bevacizumab</title>
          <description>Participants received standard 5-Flurouracil (5-FU) based chemotherapy plus bevacizumab 5 milligrams per kilograms (mg/kg) intravenous infusion every two week cycle for a maximum of 12 cycles unless they experienced progressive disease, unacceptable toxicities or participant refusal.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="50"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="38"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progressive Disease</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Investigator Decision</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Unspecified Reason</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Intent-to-treat (ITT) population included all participants enrolled in the study.</population>
      <group_list>
        <group group_id="B1">
          <title>Bevacizumab</title>
          <description>Participants received standard 5-FU based chemotherapy plus bevacizumab 5 mg/kg intravenous infusion every two week cycle for a maximum of 12 cycles unless they experienced progressive disease, unacceptable toxicities or participant refusal.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="50"/>
          </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="56.1" spread="9.71"/>
                  </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="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants Achieving Complete Resection (R0 Resection)</title>
        <description>R0 resection was defined as complete resection confirmed by pathology after pre-operative chemotherapy plus bevacizumab. Participants with R0 resections based on assessments performed at time of surgery, 48 hours post-surgery and 4 and 12 weeks after surgery were reported.</description>
        <time_frame>At time of surgery (up to 28 weeks), 48 hours post-surgery and 4 and 12 weeks after surgery (up to 40 weeks)</time_frame>
        <population>ITT population</population>
        <group_list>
          <group group_id="O1">
            <title>Bevacizumab</title>
            <description>Participants received standard 5-FU based chemotherapy plus bevacizumab 5 mg/kg intravenous infusion every two week cycle for a maximum of 12 cycles unless they experienced progressive disease, unacceptable toxicities or participant refusal.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving Complete Resection (R0 Resection)</title>
          <description>R0 resection was defined as complete resection confirmed by pathology after pre-operative chemotherapy plus bevacizumab. Participants with R0 resections based on assessments performed at time of surgery, 48 hours post-surgery and 4 and 12 weeks after surgery were reported.</description>
          <population>ITT population</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.0" lower_limit="17.9" upper_limit="44.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Achieving Incomplete Tumor Resection (R1 Resection)</title>
        <description>R1 resection was defined as achievement of incomplete tumor resection with microscopic involvement of a margin after pre-operative chemotherapy plus bevacizumab, as confirmed by pathology. Participants with R1 resections based on assessments performed at time of surgery, 48 hours post-surgery and 4 and 12 weeks after surgery were reported.</description>
        <time_frame>At time of surgery (up to 28 weeks), 48 hours post-surgery and 4 and 12 weeks after surgery (up to 40 weeks)</time_frame>
        <population>ITT population</population>
        <group_list>
          <group group_id="O1">
            <title>Bevacizumab</title>
            <description>Participants received standard 5-FU based chemotherapy plus bevacizumab 5 mg/kg intravenous infusion every two week cycle for a maximum of 12 cycles unless they experienced progressive disease, unacceptable toxicities or participant refusal.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving Incomplete Tumor Resection (R1 Resection)</title>
          <description>R1 resection was defined as achievement of incomplete tumor resection with microscopic involvement of a margin after pre-operative chemotherapy plus bevacizumab, as confirmed by pathology. Participants with R1 resections based on assessments performed at time of surgery, 48 hours post-surgery and 4 and 12 weeks after surgery were reported.</description>
          <population>ITT population</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.0" upper_limit="7.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Achieving Objective Response</title>
        <description>Objective response rate was defined as the percentage of participants who achieved either Partial Response (PR) or Complete Response (CR) per Response Evaluation Criteria In Solid Tumors (RECIST) version (v) 1.1. This is defined as the best response recorded from the start of trial treatment until disease progression (or death). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than [&lt;] 10 mm). No new lesions. PR was defined as greater than or equal to [≥] 30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.</description>
        <time_frame>Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)</time_frame>
        <population>ITT population</population>
        <group_list>
          <group group_id="O1">
            <title>Bevacizumab</title>
            <description>Participants received standard 5-FU based chemotherapy plus bevacizumab 5 mg/kg intravenous infusion every two week cycle for a maximum of 12 cycles unless they experienced progressive disease, unacceptable toxicities or participant refusal.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving Objective Response</title>
          <description>Objective response rate was defined as the percentage of participants who achieved either Partial Response (PR) or Complete Response (CR) per Response Evaluation Criteria In Solid Tumors (RECIST) version (v) 1.1. This is defined as the best response recorded from the start of trial treatment until disease progression (or death). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than [&lt;] 10 mm). No new lesions. PR was defined as greater than or equal to [≥] 30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.</description>
          <population>ITT population</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.0" lower_limit="17.9" upper_limit="44.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Disease Progression or Relapse or Death</title>
        <description>According to RECIST v1.1 Progressive Disease is defined as a 20 % or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions.</description>
        <time_frame>Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)</time_frame>
        <population>ITT population</population>
        <group_list>
          <group group_id="O1">
            <title>Bevacizumab</title>
            <description>Participants received standard 5-FU based chemotherapy plus bevacizumab 5 mg/kg intravenous infusion every two week cycle for a maximum of 12 cycles unless they experienced progressive disease, unacceptable toxicities or participant refusal.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Disease Progression or Relapse or Death</title>
          <description>According to RECIST v1.1 Progressive Disease is defined as a 20 % or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions.</description>
          <population>ITT population</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival (PFS)</title>
        <description>Progressive Disease is defined as a 20% or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions. PFS was defined as the time from initiation of study treatment to disease progression, as determined by the investigator using RECIST v1.1 criterion, or relapse after resection of liver metastases or death from any cause. Kaplan-Meier curves were used to display PFS.</description>
        <time_frame>Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)</time_frame>
        <population>ITT population</population>
        <group_list>
          <group group_id="O1">
            <title>Bevacizumab</title>
            <description>Participants received standard 5-FU based chemotherapy plus bevacizumab 5 mg/kg intravenous infusion every two week cycle for a maximum of 12 cycles unless they experienced progressive disease, unacceptable toxicities or participant refusal.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS)</title>
          <description>Progressive Disease is defined as a 20% or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions. PFS was defined as the time from initiation of study treatment to disease progression, as determined by the investigator using RECIST v1.1 criterion, or relapse after resection of liver metastases or death from any cause. Kaplan-Meier curves were used to display PFS.</description>
          <population>ITT population</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.06" lower_limit="6.70" upper_limit="13.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Probability (PP) of Being Alive and Progression Free at Months 3, 6, 9, 12, 15, and 18</title>
        <description>Progressive Disease is defined as a 20% or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions. PFS was defined as the time from initiation of study treatment to disease progression, as determined by the investigator using RECIST v1.1 criterion, or relapse after resection of liver metastases or death from any cause. The probability was estimated by Kaplan Meier curve analysis.</description>
        <time_frame>Months 3, 6, 9, 12, 15, and 18</time_frame>
        <population>ITT population; Number of participants analyzed equals (=) number of participants who had surgery.</population>
        <group_list>
          <group group_id="O1">
            <title>Bevacizumab</title>
            <description>Participants received standard 5-FU based chemotherapy plus bevacizumab 5 mg/kg intravenous infusion every two week cycle for a maximum of 12 cycles unless they experienced progressive disease, unacceptable toxicities or participant refusal.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Probability (PP) of Being Alive and Progression Free at Months 3, 6, 9, 12, 15, and 18</title>
          <description>Progressive Disease is defined as a 20% or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions. PFS was defined as the time from initiation of study treatment to disease progression, as determined by the investigator using RECIST v1.1 criterion, or relapse after resection of liver metastases or death from any cause. The probability was estimated by Kaplan Meier curve analysis.</description>
          <population>ITT population; Number of participants analyzed equals (=) number of participants who had surgery.</population>
          <units>PP of being alive and progression free</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>3 Months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="97.7" lower_limit="84.9" upper_limit="99.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 Months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="76.4" lower_limit="59.4" upper_limit="87.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>9 Months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59.5" lower_limit="40.8" upper_limit="74.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 Months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51.5" lower_limit="32.6" upper_limit="67.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>15 Months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.0" lower_limit="14.0" upper_limit="47.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>18 Months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.4" lower_limit="8.1" upper_limit="38.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Disease Relapse or Death</title>
        <time_frame>Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)</time_frame>
        <population>ITT population</population>
        <group_list>
          <group group_id="O1">
            <title>Bevacizumab</title>
            <description>Participants received standard 5-FU based chemotherapy plus bevacizumab 5 mg/kg intravenous infusion every two week cycle for a maximum of 12 cycles unless they experienced progressive disease, unacceptable toxicities or participant refusal.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Disease Relapse or Death</title>
          <population>ITT population</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Disease Free Survival (DFS)</title>
        <description>Disease Free Survival (DFS) was defined as the time from complete resection of liver metastases to disease relapse or death, for participants who achieve complete resection after pre-operative treatment with standard 5-FU based doublet regimen plus bevacizumab.</description>
        <time_frame>Complete resection date up to disease relapse or death until data cutoff on 12 May 2016 (up to approximately 3.5 years)</time_frame>
        <population>ITT population; Here, number of participants analyzed = participants who underwent study specified surgery. Participants who underwent surgery but did not achieve complete resection were censored.</population>
        <group_list>
          <group group_id="O1">
            <title>Bevacizumab</title>
            <description>Participants received standard 5-FU based chemotherapy plus bevacizumab 5 mg/kg intravenous infusion every two week cycle for a maximum of 12 cycles unless they experienced progressive disease, unacceptable toxicities or participant refusal.</description>
          </group>
        </group_list>
        <measure>
          <title>Disease Free Survival (DFS)</title>
          <description>Disease Free Survival (DFS) was defined as the time from complete resection of liver metastases to disease relapse or death, for participants who achieve complete resection after pre-operative treatment with standard 5-FU based doublet regimen plus bevacizumab.</description>
          <population>ITT population; Here, number of participants analyzed = participants who underwent study specified surgery. Participants who underwent surgery but did not achieve complete resection were censored.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.48" lower_limit="1.84" upper_limit="10.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Probability Of Being Alive and Disease Free at Months 3, 6, 9, and 12</title>
        <time_frame>Months 3, 6, 9, and 12</time_frame>
        <population>ITT population</population>
        <group_list>
          <group group_id="O1">
            <title>Bevacizumab</title>
            <description>Participants received standard 5-FU based chemotherapy plus bevacizumab 5 mg/kg intravenous infusion every two week cycle for a maximum of 12 cycles unless they experienced progressive disease, unacceptable toxicities or participant refusal.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Probability Of Being Alive and Disease Free at Months 3, 6, 9, and 12</title>
          <population>ITT population</population>
          <units>PP of being alive and disease free</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>3 Months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80.0" lower_limit="40.9" upper_limit="94.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 Months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70.0" lower_limit="32.9" upper_limit="89.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>9 Months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.0" lower_limit="12.3" upper_limit="67.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 Months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.0" lower_limit="3.1" upper_limit="47.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were recorded from the date of Screening until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Bevacizumab</title>
          <description>Participants received standard 5-FU based chemotherapy plus bevacizumab 5 mg/kg intravenous infusion every two week cycle for a maximum of 12 cycles unless they experienced progressive disease, unacceptable toxicities or participant refusal.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (17.1)</default_vocab>
        <default_assessment>Non-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="4" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Abdominal infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Scrotal infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (17.1)</default_vocab>
        <default_assessment>Non-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="26" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Bone marrow failure</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Injection site reaction</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="50"/>
              </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>The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Medical Communications</name_or_title>
      <organization>Hoffmann-LaRoche</organization>
      <phone>1-800-821-8590</phone>
      <email>genentech@druginfo.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/NCT01695772
org study id: ML28419
nct id: NCT01695772
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This open-label, single arm, multicenter study evaluated the resection rate in participants
      with colorectal cancer and previously untreated unresectable liver-only metastases after
      adding bevacizumab to 5-FU based doublet chemotherapy in the neoadjuvant setting.
      Participants receive standard 5-FU based chemotherapy plus Avastin bevacizumab 5 milligrams
      per kilogram (mg/kg) every 2 weeks for a maximum of 12 cycles combined pre- and
      postoperatively, unless they experienced progressive disease or unacceptable toxicity.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants Achieving Complete Resection (R0 Resection)
time frame: At time of surgery (up to 28 weeks), 48 hours post-surgery and 4 and 12 weeks after surgery (up to 40 weeks)
description: R0 resection was defined as complete resection confirmed by pathology after pre-operative chemotherapy plus bevacizumab. Participants with R0 resections based on assessments performed at time of surgery, 48 hours post-surgery and 4 and 12 weeks after surgery were reported.
measure: Percentage of Participants Achieving Incomplete Tumor Resection (R1 Resection)
time frame: At time of surgery (up to 28 weeks), 48 hours post-surgery and 4 and 12 weeks after surgery (up to 40 weeks)
description: R1 resection was defined as achievement of incomplete tumor resection with microscopic involvement of a margin after pre-operative chemotherapy plus bevacizumab, as confirmed by pathology. Participants with R1 resections based on assessments performed at time of surgery, 48 hours post-surgery and 4 and 12 weeks after surgery were reported.
measure: Percentage of Participants Achieving Objective Response
time frame: Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)
description: Objective response rate was defined as the percentage of participants who achieved either Partial Response (PR) or Complete Response (CR) per Response Evaluation Criteria In Solid Tumors (RECIST) version (v) 1.1. This is defined as the best response recorded from the start of trial treatment until disease progression (or death). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than [<] 10 mm). No new lesions. PR was defined as greater than or equal to [≥] 30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
measure: Number of Participants With Disease Progression or Relapse or Death
time frame: Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)
description: According to RECIST v1.1 Progressive Disease is defined as a 20 % or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions.
measure: Progression Free Survival (PFS)
time frame: Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)
description: Progressive Disease is defined as a 20% or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions. PFS was defined as the time from initiation of study treatment to disease progression, as determined by the investigator using RECIST v1.1 criterion, or relapse after resection of liver metastases or death from any cause. Kaplan-Meier curves were used to display PFS.
measure: Percent Probability (PP) of Being Alive and Progression Free at Months 3, 6, 9, 12, 15, and 18
time frame: Months 3, 6, 9, 12, 15, and 18
description: Progressive Disease is defined as a 20% or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions. PFS was defined as the time from initiation of study treatment to disease progression, as determined by the investigator using RECIST v1.1 criterion, or relapse after resection of liver metastases or death from any cause. The probability was estimated by Kaplan Meier curve analysis.
measure: Number of Participants With Disease Relapse or Death
time frame: Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)
measure: Disease Free Survival (DFS)
time frame: Complete resection date up to disease relapse or death until data cutoff on 12 May 2016 (up to approximately 3.5 years)
description: Disease Free Survival (DFS) was defined as the time from complete resection of liver metastases to disease relapse or death, for participants who achieve complete resection after pre-operative treatment with standard 5-FU based doublet regimen plus bevacizumab.
measure: Percent Probability Of Being Alive and Disease Free at Months 3, 6, 9, and 12
time frame: Months 3, 6, 9, and 12
arm group label: Bevacizumab
arm group type: Experimental
intervention type: Drug
intervention name: 5-FU based doublet chemotherapy
description: Standard 5-FU based doublet chemotherapy. Protocol did not specify any particular chemotherapy regimen. The choice of 5-FU based doublet chemotherapy was as per standard of practice and the dosage of 5-FU based doublet chemotherapy was as per product labels.
arm group label: Bevacizumab
intervention type: Drug
intervention name: bevacizumab
description: 5 mg/kg every 2 weeks, up to 12 cycles pre- and postoperatively
arm group label: Bevacizumab
other name: Avastin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: China
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Bevacizumab
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 