<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/NCT04456699</url>
  </required_header>
  <id_info>
    <org_study_id>7339-003</org_study_id>
    <secondary_id>MK-7339-003</secondary_id>
    <secondary_id>LYNK-003</secondary_id>
    <secondary_id>jRCT2031200146</secondary_id>
    <secondary_id>2019-000698-22</secondary_id>
    <nct_id>NCT04456699</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Olaparib (MK-7339) With or Without Bevacizumab Compared to Bevacizumab With a Fluoropyrimidine in Unresectable or Metastatic Colorectal Cancer (CRC) (MK-7339-003/LYNK-003)</brief_title>
  <official_title>A Phase 3 Randomized, Open-label Study to Evaluate the Efficacy and Safety of Olaparib Alone or in Combination With Bevacizumab Compared to Bevacizumab With a Fluoropyrimidine in Participants With Unresectable or Metastatic Colorectal Cancer Who Have Not Progressed Following First-line Induction (LYNK-003)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Merck Sharp &amp; Dohme LLC</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an efficacy and safety study of olaparib alone or in combination with bevacizumab&#xD;
      being compared to bevacizumab with a fluoropyrimidine in participants with unresectable or&#xD;
      metastatic colorectal cancer who have not progressed following first-line induction. The&#xD;
      primary hypotheses are: Olaparib + Bevacizumab is superior to a fluoropyrimidine +&#xD;
      Bevacizumab with respect to progression-free survival (PFS) using Response Evaluation&#xD;
      Criteria In Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central&#xD;
      review (BICR); Olaparib is superior to a fluoropyrimidine + Bevacizumab with respect to PFS&#xD;
      using RECIST 1.1 as assessed by BICR. As of amendment 5 study enrollment is being&#xD;
      discontinued and study participants randomized to one of the two experimental arms (olaparib&#xD;
      plus bevacizumab or olaparib monotherapy) must discontinue study intervention. Participants&#xD;
      who are still on study treatment will no longer have tumor response assessments by BICR.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 19, 2020</start_date>
  <completion_date type="Anticipated">July 15, 2024</completion_date>
  <primary_completion_date type="Actual">March 27, 2023</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>PFS Using RECIST 1.1 as Assessed by BICR</measure>
    <time_frame>Up to ~6 years</time_frame>
    <description>PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions is also considered PD.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Up to ~6 years</time_frame>
    <description>Overall survival is the time from randomization to death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR</measure>
    <time_frame>Up to ~6 years</time_frame>
    <description>ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR</measure>
    <time_frame>Up to ~6 years</time_frame>
    <description>For participants who demonstrate a confirmed CR or confirmed PR per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with One or More Adverse Events (AE)</measure>
    <time_frame>Up to ~6 years</time_frame>
    <description>An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Discontinuing Study Intervention Due to an AE</measure>
    <time_frame>Up to ~6 years</time_frame>
    <description>Tolerability is defined by the degree to which overt AEs of a drug can be tolerated by a participant without discontinuing from the study.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">335</enrollment>
  <condition>Metastatic Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>Olaparib + bevacizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive olaparib (300 mg twice daily [BID] oral) + Bevacizumab (5 mg/kg intravenous [IV] once every 2 weeks [Q2W]) until progressive disease or end of study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Olaparib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive olaparib (300 mg BID) oral, until progressive disease or end of study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Bevacizumab + chemotherapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive investigator's choice of either bevacizumab (7.5mg/kg IV once every three weeks (Q3W)) + capecitabine (1000mg/m^2 BID for 14 days, then 7 days off, Q3W) or bevacizumab (5 mg/kg IV Q2W) + 5-FU (2400 mg/m2 IV over 46 to 48 hours Q2W; bolus 5FU (400mg/m2) can be added prior to infusional 5FU, per local standards and at the investigator's discretion). Leucovorin or levoleucovorin 400 mg/m^2 (leucovorin) or 200 mg/m^2 (levoleucovorin) Q2W IV infusion may be added per investigator's discretion. Treatment will continue until progressive disease or end of study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Olaparib</intervention_name>
    <description>300 mg BID, oral until progressive disease or end of study</description>
    <arm_group_label>Olaparib</arm_group_label>
    <arm_group_label>Olaparib + bevacizumab</arm_group_label>
    <other_name>LYNPARZA^TM</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5-FU</intervention_name>
    <description>2400 mg/m^2 over 46 to 48 hours Q2W IV infusion until disease progression or end of study; bolus 5FU (400mg/m2) can be added prior to infusional 5FU, per local standards and at the investigator's discretion</description>
    <arm_group_label>Bevacizumab + chemotherapy</arm_group_label>
    <other_name>Fluorouracil</other_name>
    <other_name>Adrucil</other_name>
    <other_name>Efudex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bevacizumab</intervention_name>
    <description>5 mg/kg or 7.5 mg/kg Q2W or Q3W IV infusion until progressive disease or end of study</description>
    <arm_group_label>Bevacizumab + chemotherapy</arm_group_label>
    <arm_group_label>Olaparib + bevacizumab</arm_group_label>
    <other_name>MVASI^TM</other_name>
    <other_name>Avastin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine</intervention_name>
    <description>1000mg/m^2 oral capsule BID for 14 days, then 7 days off, Q3W) until progressive disease or end of study</description>
    <arm_group_label>Bevacizumab + chemotherapy</arm_group_label>
    <other_name>XELODA^®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Leucovorin/ levoleucovorin</intervention_name>
    <description>400 mg/m^2 (leucovorin) or 200 mg/m^2 (levoleucovorin) may be added to Bevacizumab + 5FU per investigator's discretion Q2W IV infusion until progressive disease or end of study</description>
    <arm_group_label>Bevacizumab + chemotherapy</arm_group_label>
    <other_name>Folinic Acid</other_name>
    <other_name>Fusilev^®</other_name>
    <other_name>Khapzory^TM</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Has a histologically-confirmed metastatic or unresectable (Stage IV as defined by&#xD;
             American Joint Committee on Cancer (AJCC eighth edition) colorectal adenocarcinoma&#xD;
             (National Comprehensive Cancer Network [NCCN] 2018).&#xD;
&#xD;
          2. Has not progressed (ie, achieved a stable disease [SD], partial response [PR], or&#xD;
             complete response [CR]) after a first-line induction course of at least 6 cycles of&#xD;
             FOLFOX + bevacizumab or 4 cycles of CAPOX + bevacizumab as first-line therapy.&#xD;
&#xD;
               -  Participants must not have received an investigational agent during their&#xD;
                  induction course.&#xD;
&#xD;
               -  Determination of best overall response (SD/PR/CR) will be made by the&#xD;
                  investigator.&#xD;
&#xD;
               -  Non-PD will be verified by BICR prior to randomization based on the images&#xD;
                  submitted to imaging contract research organization (iCRO) as described in&#xD;
                  inclusion criterion 4.&#xD;
&#xD;
               -  &quot;First-line therapy&quot; is defined as the first systemic chemotherapy regimen given&#xD;
                  for the diagnosis of unresectable or metastatic CRC. Participants may have&#xD;
                  received prior adjuvant/neoadjuvant chemotherapy for CRC, as long as it was&#xD;
                  completed at least 6 months prior to initiation of first-line CAPOX + bevacizumab&#xD;
                  or FOLFOX + bevacizumab induction treatment.&#xD;
&#xD;
          3. Has experienced unacceptable toxicity to oxaliplatin that, in the opinion of the&#xD;
             treating physician, requires/required the discontinuation of oxaliplatin. Note: As an&#xD;
             example, unacceptable toxicity may include (but is not limited to) severe or prolonged&#xD;
             neurotoxicity.&#xD;
&#xD;
             • Participants must be randomized within a minimum of 2 weeks and a maximum of 6 weeks&#xD;
             after their last dose of CAPOX + bevacizumab or FOLFOX + bevacizumab (last dose is the&#xD;
             day of the last infusion that contained oxaliplatin).&#xD;
&#xD;
          4. Has provided to the iCRO 1 set of baseline radiographic images taken before or during&#xD;
             the CAPOX + bevacizumab or FOLFOX + bevacizumab induction period and at least 42 days&#xD;
             prior to the imaging performed during Screening. Tumor imaging at Screening must be&#xD;
             performed within 28 days prior to the date of randomization.&#xD;
&#xD;
          5. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within&#xD;
             10 days prior to randomization.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Has known hypersensitivity to the components and/or excipients in bevacizumab, 5-FU,&#xD;
             capecitabine, or olaparib.&#xD;
&#xD;
          2. Has known active central nervous system (CNS) metastases and/or carcinomatous&#xD;
             meningitis. Participants with previously treated brain metastases may participate&#xD;
             provided they are radiologically stable (ie, without evidence of progression for at&#xD;
             least 28 days by repeat imaging (note that the repeat imaging should be performed&#xD;
             during study screening), clinically stable and without requirement of steroid&#xD;
             intervention for at least 14 days prior to first dose of study intervention.&#xD;
&#xD;
          3. Has an active infection requiring systemic therapy.&#xD;
&#xD;
          4. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is&#xD;
             required unless mandated by local health authority.&#xD;
&#xD;
          5. Has a known history of or is positive for hepatitis B surface antigen (HBsAg reactive)&#xD;
             or hepatitis C ribonucleic acid (HCV RNA [qualitative]) is detected). Note: No testing&#xD;
             for hepatitis B and hepatitis C is required unless mandated by local health authority.&#xD;
&#xD;
          6. Has a known psychiatric or substance abuse disorder that would interfere with the&#xD;
             participant's ability to cooperate with the requirements of the study.&#xD;
&#xD;
          7. Has myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) or with features&#xD;
             suggestive of MDS/AML.&#xD;
&#xD;
          8. Has hemoptysis or hematemesis within 28 days prior to randomization.&#xD;
&#xD;
          9. Has evidence of bleeding diathesis or significant coagulopathy (in the absence of&#xD;
             anticoagulation).&#xD;
&#xD;
         10. Has clinically significant bleeding within 28 days prior to randomization.&#xD;
&#xD;
         11. Is considered a poor medical risk due to a serious, uncontrolled medical disorder,&#xD;
             nonmalignant systemic disease or active, uncontrolled infection. Examples include, but&#xD;
             are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months)&#xD;
             myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord&#xD;
             compression, superior vena cava syndrome, extensive interstitial bilateral lung&#xD;
             disease on high-resolution computed tomography (HRCT) scan or any psychiatric disorder&#xD;
             that prohibits obtaining informed consent.&#xD;
&#xD;
         12. Has 1 or more conditions that, in the opinion of the treating physician, make the&#xD;
             participant ineligible for treatment with bevacizumab. These conditions may include:&#xD;
&#xD;
               -  Uncontrolled hypertension (systolic blood pressure [SBP] &gt;150 mm Hg or diastolic&#xD;
                  blood pressure [DBP] &gt;100 mm Hg) or a history of hypertensive crisis or&#xD;
                  hypertensive encephalopathy&#xD;
&#xD;
               -  Arterial thromboembolic events (eg, myocardial infarction, cerebral infarction)&#xD;
&#xD;
               -  History of nephrotic syndrome or moderate proteinuria&#xD;
&#xD;
               -  History of gastrointestinal perforation&#xD;
&#xD;
               -  History of non-gastrointestinal fistula formation&#xD;
&#xD;
               -  History of possible reversible encephalopathy syndrome (RPLS)&#xD;
&#xD;
         13. Has received prior systemic anticancer therapy (other than CAPOX + bevacizumab or&#xD;
             FOLFOX + bevacizumab induction) including investigational agents within 28 days prior&#xD;
             to randomization. Note: Participants must have recovered from all AEs due to previous&#xD;
             therapies to ≤Grade 1 or baseline. Participants with persistent alopecia or Grade ≤3&#xD;
             neuropathy are eligible.&#xD;
&#xD;
         14. Has received prior therapy with olaparib or with any other polyadenosine&#xD;
             5'-diphosphoribose polymerase (PARP) inhibitor.&#xD;
&#xD;
         15. Is currently receiving either strong (eg, itraconazole, telithromycin, clarithromycin,&#xD;
             protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir,&#xD;
             nelfinavir, boceprevir, telaprevir) or moderate (eg, ciprofloxacin, erythromycin,&#xD;
             diltiazem, fluconazole, verapamil) inhibitors of cytochrome P450 3A4 (CYP3A4) that&#xD;
             cannot be discontinued for the duration of the study. The required washout period&#xD;
             prior to randomization is 2 weeks.&#xD;
&#xD;
         16. Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin,&#xD;
             rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or&#xD;
             moderate (eg. bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be&#xD;
             discontinued for the duration of the study. The required washout period prior to&#xD;
             randomization is 5 weeks for phenobarbital and 3 weeks for other agents.&#xD;
&#xD;
         17. Has undergone major surgery within 2 weeks of randomization or has not recovered&#xD;
             adequately from toxicities and/or complications from any major surgery prior to&#xD;
             randomization.&#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>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Merck Sharp &amp; Dohme LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Providence Saint Joseph Medical Center, Disney Family Cancer ( Site 1392)</name>
      <address>
        <city>Burbank</city>
        <state>California</state>
        <zip>91505</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Joseph Heritage Healthcare-Oncology ( Site 1383)</name>
      <address>
        <city>Fullerton</city>
        <state>California</state>
        <zip>92835</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC Health Memorial Hospital ( Site 1401)</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80909</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Poudre Valley Health System ( Site 1402)</name>
      <address>
        <city>Fort Collins</city>
        <state>Colorado</state>
        <zip>80528</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Cancer &amp; Blood Center, LLC ( Site 1381)</name>
      <address>
        <city>Athens</city>
        <state>Georgia</state>
        <zip>30607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago ( Site 1357)</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois Cancer Care, PC ( Site 1352)</name>
      <address>
        <city>Peoria</city>
        <state>Illinois</state>
        <zip>61615</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>James Graham Brown Cancer Center ( Site 1393)</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Medical Center New Orleans ( Site 1365)</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New England Cancer Specialists ( Site 1422)</name>
      <address>
        <city>Scarborough</city>
        <state>Maine</state>
        <zip>04074</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer &amp; Hematology Centers of Western Michigan ( Site 1358)</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hattiesburg Clinic Hematology/Oncology ( Site 1418)</name>
      <address>
        <city>Hattiesburg</city>
        <state>Mississippi</state>
        <zip>39401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University in St. Louis ( Site 1384)</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Vincent Frontier Cancer Center-Research ( Site 1414)</name>
      <address>
        <city>Billings</city>
        <state>Montana</state>
        <zip>59102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHI Health St. Francis ( Site 1406)</name>
      <address>
        <city>Grand Island</city>
        <state>Nebraska</state>
        <zip>68803</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Partners of Nebraska ( Site 1353)</name>
      <address>
        <city>Lincoln</city>
        <state>Nebraska</state>
        <zip>68510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Portland Medical Center ( Site 1400)</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University ( Site 1411)</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allegheny Singer Research Institute ( Site 1364)</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West Cancer Center - East Campus ( Site 1396)</name>
      <address>
        <city>Germantown</city>
        <state>Tennessee</state>
        <zip>38138</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center ( Site 1362)</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor Scott &amp; White Medical Center - Temple ( Site 1397)</name>
      <address>
        <city>Temple</city>
        <state>Texas</state>
        <zip>76508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Blue Ridge Cancer Care ( Site 1374)</name>
      <address>
        <city>Roanoke</city>
        <state>Virginia</state>
        <zip>24014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St George Hospital ( Site 0052)</name>
      <address>
        <city>Kogarah</city>
        <state>New South Wales</state>
        <zip>2217</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Liverpool Hospital ( Site 0055)</name>
      <address>
        <city>Liverpool</city>
        <state>New South Wales</state>
        <zip>2170</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Brisbane and Women s Hospital ( Site 0054)</name>
      <address>
        <city>Herston</city>
        <state>Queensland</state>
        <zip>4029</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth Hospital ( Site 0053)</name>
      <address>
        <city>Woodville South</city>
        <state>South Australia</state>
        <zip>5011</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Monash Health ( Site 0050)</name>
      <address>
        <city>Clayton</city>
        <state>Victoria</state>
        <zip>3168</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peninsula Health Frankston Hospital ( Site 0056)</name>
      <address>
        <city>Frankston</city>
        <state>Victoria</state>
        <zip>3199</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Imelda vzw ( Site 0110)</name>
      <address>
        <city>Bonheiden</city>
        <state>Antwerpen</state>
        <zip>2820</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AZ Klina ( Site 0106)</name>
      <address>
        <city>Brasschaat</city>
        <state>Antwerpen</state>
        <zip>2930</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Antwerpen ( Site 0108)</name>
      <address>
        <city>Edegem</city>
        <state>Antwerpen</state>
        <zip>2650</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCL Saint Luc ( Site 0100)</name>
      <address>
        <city>Brussels</city>
        <state>Bruxelles-Capitale, Region De</state>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OLV Ziekenhuis ( Site 0109)</name>
      <address>
        <city>Aalst</city>
        <state>Oost-Vlaanderen</state>
        <zip>9300</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Gent ( Site 0101)</name>
      <address>
        <city>Gent</city>
        <state>Oost-Vlaanderen</state>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Gasthuisberg ( Site 0102)</name>
      <address>
        <city>Leuven</city>
        <state>Vlaams-Brabant</state>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AZ Groeninge ( Site 0105)</name>
      <address>
        <city>Kortrijk</city>
        <state>West-Vlaanderen</state>
        <zip>8500</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dr. Everett Chalmers Regional Hospital ( Site 0204)</name>
      <address>
        <city>Fredericton</city>
        <state>New Brunswick</state>
        <zip>E3B 5N5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Moncton Hospital - Horizon Health Network ( Site 0201)</name>
      <address>
        <city>Moncton</city>
        <state>New Brunswick</state>
        <zip>E1C 6Z8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Margaret Cancer Centre ( Site 0209)</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1X6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Cite de la Sante de Laval ( Site 0203)</name>
      <address>
        <city>Laval</city>
        <state>Quebec</state>
        <zip>H7M 3L9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McGill University Health Centre ( Site 0207)</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H4A 3J1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0202)</name>
      <address>
        <city>Sherbrooke</city>
        <state>Quebec</state>
        <zip>J1H 5N4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Investigación del Cáncer James Lind ( Site 0251)</name>
      <address>
        <city>Temuco</city>
        <state>Araucania</state>
        <zip>4780000</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sociedad Oncovida S.A. ( Site 0250)</name>
      <address>
        <city>Santiago</city>
        <state>Region M. De Santiago</state>
        <zip>7510032</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clínica San Carlos de Apoquindo Red Salud UC Christus ( Site 0252)</name>
      <address>
        <city>Santiago</city>
        <state>Region M. De Santiago</state>
        <zip>7620002</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 0353)</name>
      <address>
        <city>Valledupar</city>
        <state>Cesar</state>
        <zip>200001</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncomedica S.A. ( Site 0352)</name>
      <address>
        <city>Monteria</city>
        <state>Cordoba</state>
        <zip>230002</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Administradora Country SA - Clinica del Country ( Site 0350)</name>
      <address>
        <city>Bogota</city>
        <state>Distrito Capital De Bogota</state>
        <zip>110221</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Nacional de Cancerologia E.S.E ( Site 0362)</name>
      <address>
        <city>Bogota</city>
        <state>Distrito Capital De Bogota</state>
        <zip>110321</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncologos del Occidente ( Site 0364)</name>
      <address>
        <city>Pereira</city>
        <state>Risaralda</state>
        <zip>660001</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundacion Cardiovascular de Colombia ( Site 0360)</name>
      <address>
        <city>Bucaramanga</city>
        <state>Santander</state>
        <zip>681002</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hemato Oncologos S.A. ( Site 0355)</name>
      <address>
        <city>Cali</city>
        <state>Valle Del Cauca</state>
        <zip>760042</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>C.H.U. de Strasbourg Hopital de Hautepierre ( Site 0464)</name>
      <address>
        <city>Strasbourg</city>
        <state>Bas-Rhin</state>
        <zip>67098</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut de Cancerologie de l Ouest Centre Rene Gauducheau ( Site 0455)</name>
      <address>
        <city>Saint-Herblain</city>
        <state>Bretagne</state>
        <zip>44805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Jean Minjoz ( Site 0450)</name>
      <address>
        <city>Besancon</city>
        <state>Doubs</state>
        <zip>25000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Bordeaux Haut-Leveque ( Site 0457)</name>
      <address>
        <city>Pessac Cedex</city>
        <state>Gironde</state>
        <zip>33604</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Saint Eloi ( Site 0467)</name>
      <address>
        <city>Montpellier</city>
        <state>Herault</state>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Leon Berard ( Site 0459)</name>
      <address>
        <city>Lyon</city>
        <state>Rhone-Alpes</state>
        <zip>69008</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Europeen Georges Pompidou ( Site 0452)</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Ulm ( Site 0500)</name>
      <address>
        <city>Ulm</city>
        <state>Baden-Wurttemberg</state>
        <zip>89081</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Josef und St. Elisabeth Hospital gGmbH-Hematology, oncology and palliative medicine ( Site 0503)</name>
      <address>
        <city>Bochum</city>
        <state>Nordrhein-Westfalen</state>
        <zip>44791</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0504)</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Facharztzentrum Eppendorf ( Site 0501)</name>
      <address>
        <city>Hamburg</city>
        <zip>20249</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bekes Megyei Kozponti Korhaz - Pandy Kalman Tagkorhaza ( Site 1432)</name>
      <address>
        <city>Gyula</city>
        <state>Bekes</state>
        <zip>5700</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Okta-Klinikai Onkológiai és Sugárterápiás Ce</name>
      <address>
        <city>Miskolc</city>
        <state>Borsod-Abauj-Zemplen</state>
        <zip>3526</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Debreceni Egyetem Klinikai Kozpont ( Site 1426)</name>
      <address>
        <city>Debrecen</city>
        <state>Hajdu-Bihar</state>
        <zip>4032</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 1427)</name>
      <address>
        <city>Szolnok</city>
        <state>Jasz-Nagykun-Szolnok</state>
        <zip>5000</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zala Megyei Szent Rafael Korhaz ( Site 1429)</name>
      <address>
        <city>Zalaegerszeg</city>
        <state>Zala</state>
        <zip>8900</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Orszagos Onkologiai Intezet ( Site 1431)</name>
      <address>
        <city>Budapest</city>
        <zip>1122</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aichi Cancer Center Hospital ( Site 0658)</name>
      <address>
        <city>Nagoya</city>
        <state>Aichi</state>
        <zip>464-8681</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center Hospital East ( Site 0650)</name>
      <address>
        <city>Kashiwa</city>
        <state>Chiba</state>
        <zip>2778577</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Hospital Organization Shikoku Cancer Center ( Site 0652)</name>
      <address>
        <city>Matsuyama</city>
        <state>Ehime</state>
        <zip>791-0280</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Marianna University School of Medicine Hospital ( Site 0657)</name>
      <address>
        <city>Kawasaki</city>
        <state>Kanagawa</state>
        <zip>216-8511</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saitama Cancer Center ( Site 0653)</name>
      <address>
        <city>Kitaadachi-gun</city>
        <state>Saitama</state>
        <zip>362-0806</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shizuoka Cancer Center Hospital and Research Institute ( Site 0655)</name>
      <address>
        <city>Sunto-gun</city>
        <state>Shizuoka</state>
        <zip>411-8777</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chiba Cancer Center ( Site 0656)</name>
      <address>
        <city>Chiba</city>
        <zip>260-8717</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Hospital Organization Kyushu Cancer Center ( Site 0654)</name>
      <address>
        <city>Fukuoka</city>
        <zip>811-1395</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center Hospital ( Site 0651)</name>
      <address>
        <city>Tokyo</city>
        <zip>104-0045</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Cancer Institute Hospital of JFCR ( Site 0659)</name>
      <address>
        <city>Tokyo</city>
        <zip>135-8550</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center ( Site 0952)</name>
      <address>
        <city>Songpagu</city>
        <state>Seoul</state>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kyungpook National University Chilgok Hospital ( Site 0956)</name>
      <address>
        <city>Daegu</city>
        <state>Taegu-Kwangyokshi</state>
        <zip>41404</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Korea University Anam Hospital ( Site 0955)</name>
      <address>
        <city>Seoul</city>
        <zip>02841</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital ( Site 0950)</name>
      <address>
        <city>Seoul</city>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Severance Hospital Yonsei University Health System ( Site 0951)</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center ( Site 0954)</name>
      <address>
        <city>Seoul</city>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Catholic University of Korea St. Mary s Hospital ( Site 0953)</name>
      <address>
        <city>Seoul</city>
        <zip>06591</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Daugavpils Regional Hospital ( Site 1502)</name>
      <address>
        <city>Daugavpils</city>
        <zip>5417</zip>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>P. Stradina Clinical University Hospital ( Site 1500)</name>
      <address>
        <city>Riga</city>
        <zip>LV-1002</zip>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Riga East Clinical University Hospital ( Site 1501)</name>
      <address>
        <city>Riga</city>
        <zip>LV-1079</zip>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LSMUL Kauno Klinikos ( Site 1528)</name>
      <address>
        <city>Kaunas</city>
        <zip>50161</zip>
        <country>Lithuania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nacionalinis Vezio Institutas ( Site 1527)</name>
      <address>
        <city>Vilnius</city>
        <zip>08406</zip>
        <country>Lithuania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vilniaus Universiteto Ligonine Santaros Klinikos ( Site 1526)</name>
      <address>
        <city>Vilnius</city>
        <zip>08460</zip>
        <country>Lithuania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arkhangelsk Clinical Oncological Dispensary ( Site 1113)</name>
      <address>
        <city>Arkhangelsk</city>
        <state>Arkhangel Skaya Oblast</state>
        <zip>163045</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GBUZ Republican Clinical Oncological Dispensary-Antitumor drug therapy department ( Site 1130)</name>
      <address>
        <city>Ufa</city>
        <state>Baskortostan, Respublika</state>
        <zip>450054</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 1121)</name>
      <address>
        <city>Krasnoyarsk</city>
        <state>Krasnoyarskiy Kray</state>
        <zip>660133</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MEDSI Clinical Hospital on Pyatnitsky Highway-Departmentof Antitumor Drug therapy ( Site 1129)</name>
      <address>
        <city>Krasnogorsk</city>
        <state>Moskovskaya Oblast</state>
        <zip>143442</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Medical and Surgical Center n.a. N.I.Pirogov ( Site 1126)</name>
      <address>
        <city>Moscow</city>
        <state>Moskva</state>
        <zip>105203</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>N.N. Blokhin NMRCO ( Site 1106)</name>
      <address>
        <city>Moscow</city>
        <state>Moskva</state>
        <zip>115478</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>First Moscow State Medical University n.a. I.M.Sechenov ( Site 1127)</name>
      <address>
        <city>Moscow</city>
        <state>Moskva</state>
        <zip>119991</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MROI n.a. P.A. Herzen - branch of FSBI NMICR of MoH of Russia ( Site 1128)</name>
      <address>
        <city>Moscow</city>
        <state>Moskva</state>
        <zip>125284</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City Clinical Oncology Center ( Site 1114)</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Sankt-Peterburg</state>
        <zip>198255</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandton Oncology Medical Group PTY LTD ( Site 0900)</name>
      <address>
        <city>Sandton</city>
        <state>Gauteng</state>
        <zip>2196</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Oncology Centre ( Site 0903)</name>
      <address>
        <city>Durban</city>
        <state>Limpopo</state>
        <zip>4001</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancercare Rondebosch Oncology ( Site 0904)</name>
      <address>
        <city>Rondebosch</city>
        <state>Western Cape</state>
        <zip>7700</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario de Elche ( Site 1155)</name>
      <address>
        <city>Elche</city>
        <state>Alicante</state>
        <zip>03203</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Central de Asturias ( Site 1153)</name>
      <address>
        <city>Oviedo</city>
        <state>Asturias</state>
        <zip>33011</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Vall D Hebron ( Site 1151)</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Gregorio Maranon ( Site 1152)</name>
      <address>
        <city>Madrid</city>
        <zip>28009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital 12 de Octubre de Madrid ( Site 1150)</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inonu Universitesi Medical Fakultesi ( Site 1207)</name>
      <address>
        <city>Malatya</city>
        <state>Adana</state>
        <zip>44280</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baskent University Adana Training Hospital ( Site 1205)</name>
      <address>
        <city>Adana</city>
        <zip>01250</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hacettepe University Faculty of Medicine ( Site 1200)</name>
      <address>
        <city>Ankara</city>
        <zip>06230</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gazi Universitesi Tip Fakultesi ( Site 1215)</name>
      <address>
        <city>Ankara</city>
        <zip>06500</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Trakya Universitesi Tip Fakultesi ( Site 1210)</name>
      <address>
        <city>Edirne</city>
        <zip>22030</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 1202)</name>
      <address>
        <city>Istanbul</city>
        <zip>34098</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prof. Dr. Cemil Tascioglu Sehir Hastanesi ( Site 1216)</name>
      <address>
        <city>Istanbul</city>
        <zip>34384</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 1214)</name>
      <address>
        <city>Istanbul</city>
        <zip>34722</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kartal Dr. Lutfi Kirdar Egitim ve Arast Hast ( Site 1211)</name>
      <address>
        <city>Istanbul</city>
        <zip>34890</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ege Universitesi Tip Fakultesi Tulay Aktas Onkoloji Hastanesi ( Site 1204)</name>
      <address>
        <city>Izmir</city>
        <zip>35040</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Necmettin Erbakan Universitesi Meram Tip Fakultesi ( Site 1203)</name>
      <address>
        <city>Konya</city>
        <zip>42080</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical center Medikal Plaza of Ecodnipro LLC ( Site 1317)</name>
      <address>
        <city>Dnipro</city>
        <state>Dnipropetrovska Oblast</state>
        <zip>49055</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Communal non profit enterprise Regional Clinical Oncology Center ( Site 1304)</name>
      <address>
        <city>Kharkiv</city>
        <state>Kharkivska Oblast</state>
        <zip>61070</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Center of Yuriy Spizhenko LLC.-Clinical Trial ( Site 1319)</name>
      <address>
        <city>Kapitanivka Village</city>
        <state>Kyivska Oblast</state>
        <zip>08111</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Center Asklepion LLC ( Site 1309)</name>
      <address>
        <city>Khodosivka</city>
        <state>Kyivska Oblast</state>
        <zip>08173</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Center Verum ( Site 1318)</name>
      <address>
        <city>Kyiv</city>
        <state>Kyivska Oblast</state>
        <zip>03039</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shalimov s NI of Surgery and Transplantation ( Site 1321)</name>
      <address>
        <city>Kyiv</city>
        <state>Kyivska Oblast</state>
        <zip>03126</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical center of the Limited Liability Company Yulis ( Site 1314)</name>
      <address>
        <city>Zaporizhzhia</city>
        <state>Zaporizka Oblast</state>
        <zip>69035</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dobrobut Medical Center ( Site 1320)</name>
      <address>
        <city>Kyiv</city>
        <zip>03151</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Canada</country>
    <country>Chile</country>
    <country>Colombia</country>
    <country>France</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Latvia</country>
    <country>Lithuania</country>
    <country>Russian Federation</country>
    <country>South Africa</country>
    <country>Spain</country>
    <country>Turkey</country>
    <country>Ukraine</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://merckoncologyclinicaltrials.com</url>
    <description>Merck Oncology Clinical Trials Information</description>
  </link>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 2, 2020</study_first_posted>
  <last_update_submitted>April 5, 2023</last_update_submitted>
  <last_update_submitted_qc>April 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>colorectal cancer</keyword>
  <keyword>CRC</keyword>
  <keyword>Olaparib</keyword>
  <keyword>Bevacizumab</keyword>
  <keyword>FOLFOX</keyword>
  <keyword>5-FU</keyword>
  <keyword>fluorouracil</keyword>
  <keyword>folinic acid</keyword>
  <keyword>oxaliplatin</keyword>
  <keyword>CAPOX</keyword>
  <keyword>capecitabine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leucovorin</mesh_term>
    <mesh_term>Bevacizumab</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Capecitabine</mesh_term>
    <mesh_term>Olaparib</mesh_term>
    <mesh_term>Levoleucovorin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf</ipd_description>
    <ipd_url>http://engagezone.msd.com/ds_documentation.php</ipd_url>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04456699
org study id: 7339-003
secondary id: MK-7339-003
secondary id: LYNK-003
secondary id: jRCT2031200146
secondary id: 2019-000698-22
nct id: NCT04456699
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is an efficacy and safety study of olaparib alone or in combination with bevacizumab
      being compared to bevacizumab with a fluoropyrimidine in participants with unresectable or
      metastatic colorectal cancer who have not progressed following first-line induction. The
      primary hypotheses are: Olaparib + Bevacizumab is superior to a fluoropyrimidine +
      Bevacizumab with respect to progression-free survival (PFS) using Response Evaluation
      Criteria In Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central
      review (BICR); Olaparib is superior to a fluoropyrimidine + Bevacizumab with respect to PFS
      using RECIST 1.1 as assessed by BICR. As of amendment 5 study enrollment is being
      discontinued and study participants randomized to one of the two experimental arms (olaparib
      plus bevacizumab or olaparib monotherapy) must discontinue study intervention. Participants
      who are still on study treatment will no longer have tumor response assessments by BICR.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: PFS Using RECIST 1.1 as Assessed by BICR
time frame: Up to ~6 years
description: PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions is also considered PD.
measure: Overall Survival (OS)
time frame: Up to ~6 years
description: Overall survival is the time from randomization to death due to any cause.
measure: Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR
time frame: Up to ~6 years
description: ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
measure: Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR
time frame: Up to ~6 years
description: For participants who demonstrate a confirmed CR or confirmed PR per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death.
measure: Number of Participants with One or More Adverse Events (AE)
time frame: Up to ~6 years
description: An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention
measure: Number of Participants Discontinuing Study Intervention Due to an AE
time frame: Up to ~6 years
description: Tolerability is defined by the degree to which overt AEs of a drug can be tolerated by a participant without discontinuing from the study.
arm group label: Olaparib + bevacizumab
arm group type: Experimental
description: Participants will receive olaparib (300 mg twice daily [BID] oral) + Bevacizumab (5 mg/kg intravenous [IV] once every 2 weeks [Q2W]) until progressive disease or end of study.
arm group label: Olaparib
arm group type: Experimental
description: Participants will receive olaparib (300 mg BID) oral, until progressive disease or end of study.
arm group label: Bevacizumab + chemotherapy
arm group type: Active Comparator
description: Participants will receive investigator's choice of either bevacizumab (7.5mg/kg IV once every three weeks (Q3W)) + capecitabine (1000mg/m^2 BID for 14 days, then 7 days off, Q3W) or bevacizumab (5 mg/kg IV Q2W) + 5-FU (2400 mg/m2 IV over 46 to 48 hours Q2W; bolus 5FU (400mg/m2) can be added prior to infusional 5FU, per local standards and at the investigator's discretion). Leucovorin or levoleucovorin 400 mg/m^2 (leucovorin) or 200 mg/m^2 (levoleucovorin) Q2W IV infusion may be added per investigator's discretion. Treatment will continue until progressive disease or end of study.
intervention type: Drug
intervention name: Olaparib
description: 300 mg BID, oral until progressive disease or end of study
arm group label: Olaparib
arm group label: Olaparib + bevacizumab
other name: LYNPARZA^TM
intervention type: Drug
intervention name: 5-FU
description: 2400 mg/m^2 over 46 to 48 hours Q2W IV infusion until disease progression or end of study; bolus 5FU (400mg/m2) can be added prior to infusional 5FU, per local standards and at the investigator's discretion
arm group label: Bevacizumab + chemotherapy
other name: Fluorouracil
other name: Adrucil
other name: Efudex
intervention type: Drug
intervention name: Bevacizumab
description: 5 mg/kg or 7.5 mg/kg Q2W or Q3W IV infusion until progressive disease or end of study
arm group label: Bevacizumab + chemotherapy
arm group label: Olaparib + bevacizumab
other name: MVASI^TM
other name: Avastin
intervention type: Drug
intervention name: Capecitabine
description: 1000mg/m^2 oral capsule BID for 14 days, then 7 days off, Q3W) until progressive disease or end of study
arm group label: Bevacizumab + chemotherapy
other name: XELODA^®
intervention type: Drug
intervention name: Leucovorin/ levoleucovorin
description: 400 mg/m^2 (leucovorin) or 200 mg/m^2 (levoleucovorin) may be added to Bevacizumab + 5FU per investigator's discretion Q2W IV infusion until progressive disease or end of study
arm group label: Bevacizumab + chemotherapy
other name: Folinic Acid
other name: Fusilev^®
other name: Khapzory^TM
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Merck Sharp & Dohme LLC
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: Belgium
country: Canada
country: Chile
country: Colombia
country: France
country: Germany
country: Hungary
country: Japan
country: Korea, Republic of
country: Latvia
country: Lithuania
country: Russian Federation
country: South Africa
country: Spain
country: Turkey
country: Ukraine
country: United States
url: http://merckoncologyclinicaltrials.com
description: Merck Oncology Clinical Trials Information
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Leucovorin
mesh term: Bevacizumab
mesh term: Fluorouracil
mesh term: Capecitabine
mesh term: Olaparib
mesh term: Levoleucovorin
sharing ipd: Yes
ipd description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
ipd url: http://engagezone.msd.com/ds_documentation.php