<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/NCT03303495</url>
  </required_header>
  <id_info>
    <org_study_id>RECHANGE</org_study_id>
    <nct_id>NCT03303495</nct_id>
  </id_info>
  <brief_title>A Study of 2nd-line FOLFIRI ± Bevacizumab vs. Irinotecan ± Bevacizumab in mCRC</brief_title>
  <official_title>A Multinational, Randomized, Phase III Study of FOLFIRI With/Without Bevacizumab Versus Irinotecan With/Without Bevacizumab As Second-line Therapy in Patients With Metastatic Colorectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sun Yat-sen University</source>
  <brief_summary>
    <textblock>
      The primary purpose of this study is to determine the non-inferiority of overall survival&#xD;
      FOLFIRI with or without Bevacizumab compared with Irinotecan (CPT-11) with or without&#xD;
      Bevacizumab as Second-line therapy in Patient with Metastatic Colorectal Cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary endpoint: Overall survival (OS), Secondary endpoints: Progression-free survival&#xD;
      (PFS), Time to treatment failure (TTF), Overall response rate (ORR),Disease Control Rate&#xD;
      (DCR), Safety.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 14, 2011</start_date>
  <completion_date type="Anticipated">December 31, 2018</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2017</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>Overall survival</measure>
    <time_frame>Assessed until 1.5 years after the last patient enrolment</time_frame>
    <description>Time from the date of enrollment to death from any cause</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>Assessed until 1.5 years after the last patient enrolment</time_frame>
    <description>Time from the date of enrollment to the earlier of the date of confirmed progression or death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to treatment failure (TTF)</measure>
    <time_frame>Assessed until 1.5 years after the last patient enrolment</time_frame>
    <description>Time from the date of enrollment to the earlier of the date of confirmed progression, death from any cause, or discontinuation of protocol treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate (ORR)</measure>
    <time_frame>Assessed at 6, 12 week and thereafter every 8 weeks, from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 weeks</time_frame>
    <description>Proportion of eligible patients with measurable lesions with a best overall response of CR or PR assessed by the attending physician.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>Assessed at 6, 12 week and thereafter every 8 weeks, from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 weeks</time_frame>
    <description>Proportion of best overall response of CR, PR, or SD assessed by the attending physician.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adverse Events (Adverse Reactions)</measure>
    <time_frame>From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 weeks</time_frame>
    <description>The incidence of worst-grade adverse events (toxicities) on study as graded by NCI-CTCAE v 4.0 will be determined by treatment arm in all treated patients for the following events.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">280</enrollment>
  <condition>Colorectal Neoplasms</condition>
  <condition>Neoplasm Metastasis</condition>
  <condition>Intestinal Neoplasms</condition>
  <condition>Gastrointestinal Neoplasms</condition>
  <condition>Digestive System Neoplasms</condition>
  <arm_group>
    <arm_group_label>FOLFIRI +/- Bevacizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Bevacizumab 5 mg/kg IV 90-30 min Day 1; CPT-11 180 mg/m2 IV 90 min Day 1; l-LV (dl-LV) 200 mg/m2 (400 mg/m2) IV 120 min Day 1; 5-FU - bolus 400 mg/m2 IV bolus Day 1; 5-FU - infusional 2400 mg/m2 IV continuous (46 hours) Day 1 - 3</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CPT-11 +/- Bevacizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Bevacizumab 5 mg/kg IV 90-30 min Day 1; CPT-11 180 mg/m2 IV 90 min Day 1</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Bevacizumab</intervention_name>
    <description>5 mg/kg intravenously administered over 90 minutes (can be reduced to 30 minutes at the minimum) on day 1 of a 2-week cycle.</description>
    <arm_group_label>CPT-11 +/- Bevacizumab</arm_group_label>
    <arm_group_label>FOLFIRI +/- Bevacizumab</arm_group_label>
    <other_name>Avastin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CPT-11</intervention_name>
    <description>180 mg/m2 intravenously administered over 90 minutes on day 1 of a 2-week cycle</description>
    <arm_group_label>CPT-11 +/- Bevacizumab</arm_group_label>
    <arm_group_label>FOLFIRI +/- Bevacizumab</arm_group_label>
    <other_name>Irinotecan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5-FU Bolus</intervention_name>
    <description>400 mg/m2 intravenous bolus on day 1 of a 2-week cycle.</description>
    <arm_group_label>FOLFIRI +/- Bevacizumab</arm_group_label>
    <other_name>fluorouracil</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5-FU Infusion</intervention_name>
    <description>2400 mg/m2 continuous infusion over 46 hours on day 1 and 2 of a 2-week cycle.</description>
    <arm_group_label>FOLFIRI +/- Bevacizumab</arm_group_label>
    <other_name>fluorouracil</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>l-LV (dl-LV)</intervention_name>
    <description>200 (dl-LV: 400) mg/m2 intravenously administered over 120 minutes on day 1 of a 2-week cycle.</description>
    <arm_group_label>FOLFIRI +/- Bevacizumab</arm_group_label>
    <other_name>Leucovorin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically-confirmed inoperable colorectal adenocarcinoma excluding vermiform&#xD;
             appendix cancer and anal canal cancer.&#xD;
&#xD;
          2. Age ≥18 years at the time of informed consent&#xD;
&#xD;
          3. ECOG performance status (PS) of 0-2&#xD;
&#xD;
          4. Written informed consent prior to study-specific screening procedures&#xD;
&#xD;
          5. Life expectancy of at least 90 days&#xD;
&#xD;
          6. Withdrawal from first-line chemotherapy (regardless of containing molecular-targeted&#xD;
             drugs) for metastatic colorectal cancer due to intolerable toxicity or progressive&#xD;
             disease, or relapse within 180 days after the last dose of adjuvant chemotherapy.&#xD;
&#xD;
          7. Adequate organ function according to following laboratory values obtained within 14&#xD;
             days before enrolment (excluding patients who received blood transfusions or&#xD;
             hematopoietic growth factors within 14 days before the laboratory test) Neutrophil&#xD;
             count: ≥1500/mm3 Platelet count: ≥10.0 x 104/mm3 Hemoglobin: ≥9.0 g/dL Total&#xD;
             bilirubin: ≤1.5 mg/dL AST, ALT: ≤100 IU/L (≤200 IU/I if liver metastases present)&#xD;
             Serum creatinine: ≤1.5 mg/dL&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of other malignancy with a disease-free interval &lt;5 years (other than&#xD;
             curatively treated cutaneous basal cell carcinoma, curatively treated carcinoma in&#xD;
             situ of the cervix, and gastroenterological cancer confirmed to be cured by endoscopic&#xD;
             mucosal resection)&#xD;
&#xD;
          2. With massive pleural effusion or ascites requiring intervention&#xD;
&#xD;
          3. Radiological evidence of brain tumor or brain metastases&#xD;
&#xD;
          4. Active infection including hepatitis&#xD;
&#xD;
          5. Any of the following complication:&#xD;
&#xD;
             i) Gastrointestinal bleeding or gastrointestinal obstruction (including paralytic&#xD;
             ileus) ii) Symptomatic heart disease (including unstable angina, myocardial&#xD;
             infarction, and heart failure) iii) Interstitial pneumonia or pulmonary fibrosis iv)&#xD;
             Uncontrolled diabetes mellitus v) Uncontrolled diarrhea (that interferes with daily&#xD;
             activities despite adequate therapy)&#xD;
&#xD;
          6. Any of the following medical history:&#xD;
&#xD;
             Myocardial infarction: History of one episode within one year before enrollment or two&#xD;
             or more lifetime episodes i) Serious hypersensitivity to any of the study drugs ii)&#xD;
             History of adverse reaction to fluoropyrimidines suggesting dihydropyrimidine&#xD;
             dehydrogenase (DPD) deficiency&#xD;
&#xD;
          7. Previous treatment with irinotecan hydrochloride&#xD;
&#xD;
          8. Current treatment with atazanavir sulfate&#xD;
&#xD;
          9. Previous treatment with tegafur, gimeracil, and oteracil potassium within seven days&#xD;
             before enrollment&#xD;
&#xD;
         10. Pregnant or lactating females, and males and females unwilling to use contraception&#xD;
&#xD;
         11. Requires continuous treatment with systemic steroids&#xD;
&#xD;
         12. Psychiatric disability that would preclude study compliance&#xD;
&#xD;
         13. Otherwise determined by the investigator to be unsuitable for participation in the&#xD;
             study&#xD;
&#xD;
         14. Concurrent gastrointestinal perforation or history of gastrointestinal perforation&#xD;
             with 1 year before enrollment&#xD;
&#xD;
         15. History of pulmonary hemorrhage/hemoptysis ≥ Grade 2 (defined as bright red blood of&#xD;
             at least 2.5mL) within 1 month prior to enrollment.&#xD;
&#xD;
         16. History of laparotomy, thoracotomy, or intestinal resection within 28 days before&#xD;
             enrollment&#xD;
&#xD;
         17. Unhealed wound (except suture wounds from implantation of a central venous port),&#xD;
             gastrointestinal ulcer, or traumatic fracture&#xD;
&#xD;
         18. Current or recent (within 1 year) thromboembolism or cerebrovascular disease&#xD;
&#xD;
         19. Currently receiving or requires anticoagulation therapy (&gt; 325 mg/day of aspirin)&#xD;
&#xD;
         20. Bleeding diathesis, coagulopathy, or coagulation factor abnormality (INR ≥1.5 within&#xD;
             14 days before enrollment)&#xD;
&#xD;
         21. Uncontrolled hypertension&#xD;
&#xD;
         22. Urine dipstick for proteinuria &gt;+2&#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_contact>
    <last_name>Ruihua Xu, MD, PhD</last_name>
    <phone>87343333</phone>
    <email>xurh@sysucc.org.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>Cancer center of Sun Yat-sen University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rui-Hua Xu, MD, PhD</last_name>
      <phone>86-020-87343333</phone>
      <email>xurh@sysucc.org.cn</email>
    </contact>
    <contact_backup>
      <last_name>De-shen Wang, MD, PhD</last_name>
      <phone>86-020-87343351</phone>
      <email>wangdsh@sysucc.org.cn</email>
    </contact_backup>
    <investigator>
      <last_name>De-shen Wang, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Rui-hua Xu, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>September 23, 2017</study_first_submitted>
  <study_first_submitted_qc>October 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 6, 2017</study_first_posted>
  <last_update_submitted>October 2, 2017</last_update_submitted>
  <last_update_submitted_qc>October 2, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 6, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>Ruihua Xu</investigator_full_name>
    <investigator_title>Professor and President</investigator_title>
  </responsible_party>
  <keyword>FOLFIRI</keyword>
  <keyword>CPT-11</keyword>
  <keyword>Bevacizumab</keyword>
  <keyword>2nd-line metastatic colorectal cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Colorectal Neoplasms</mesh_term>
    <mesh_term>Gastrointestinal Neoplasms</mesh_term>
    <mesh_term>Digestive System Neoplasms</mesh_term>
    <mesh_term>Intestinal 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>Irinotecan</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_info_type>Study Protocol</ipd_info_type>
  </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/NCT03303495
org study id: RECHANGE
nct id: NCT03303495
lead sponsor: 
The primary purpose of this study is to determine the non-inferiority of overall survival
      FOLFIRI with or without Bevacizumab compared with Irinotecan (CPT-11) with or without
      Bevacizumab as Second-line therapy in Patient with Metastatic Colorectal Cancer.
Primary endpoint: Overall survival (OS), Secondary endpoints: Progression-free survival
      (PFS), Time to treatment failure (TTF), Overall response rate (ORR),Disease Control Rate
      (DCR), Safety.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall survival
time frame: Assessed until 1.5 years after the last patient enrolment
description: Time from the date of enrollment to death from any cause
measure: Progression-free survival (PFS)
time frame: Assessed until 1.5 years after the last patient enrolment
description: Time from the date of enrollment to the earlier of the date of confirmed progression or death from any cause.
measure: Time to treatment failure (TTF)
time frame: Assessed until 1.5 years after the last patient enrolment
description: Time from the date of enrollment to the earlier of the date of confirmed progression, death from any cause, or discontinuation of protocol treatment.
measure: Overall Response Rate (ORR)
time frame: Assessed at 6, 12 week and thereafter every 8 weeks, from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 weeks
description: Proportion of eligible patients with measurable lesions with a best overall response of CR or PR assessed by the attending physician.
measure: Disease Control Rate (DCR)
time frame: Assessed at 6, 12 week and thereafter every 8 weeks, from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 weeks
description: Proportion of best overall response of CR, PR, or SD assessed by the attending physician.
measure: Incidence of Adverse Events (Adverse Reactions)
time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 weeks
description: The incidence of worst-grade adverse events (toxicities) on study as graded by NCI-CTCAE v 4.0 will be determined by treatment arm in all treated patients for the following events.
arm group label: FOLFIRI +/- Bevacizumab
arm group type: Experimental
description: Bevacizumab 5 mg/kg IV 90-30 min Day 1; CPT-11 180 mg/m2 IV 90 min Day 1; l-LV (dl-LV) 200 mg/m2 (400 mg/m2) IV 120 min Day 1; 5-FU - bolus 400 mg/m2 IV bolus Day 1; 5-FU - infusional 2400 mg/m2 IV continuous (46 hours) Day 1 - 3
arm group label: CPT-11 +/- Bevacizumab
arm group type: Experimental
description: Bevacizumab 5 mg/kg IV 90-30 min Day 1; CPT-11 180 mg/m2 IV 90 min Day 1
intervention type: Biological
intervention name: Bevacizumab
description: 5 mg/kg intravenously administered over 90 minutes (can be reduced to 30 minutes at the minimum) on day 1 of a 2-week cycle.
arm group label: CPT-11 +/- Bevacizumab
arm group label: FOLFIRI +/- Bevacizumab
other name: Avastin
intervention type: Drug
intervention name: CPT-11
description: 180 mg/m2 intravenously administered over 90 minutes on day 1 of a 2-week cycle
arm group label: CPT-11 +/- Bevacizumab
arm group label: FOLFIRI +/- Bevacizumab
other name: Irinotecan
intervention type: Drug
intervention name: 5-FU Bolus
description: 400 mg/m2 intravenous bolus on day 1 of a 2-week cycle.
arm group label: FOLFIRI +/- Bevacizumab
other name: fluorouracil
intervention type: Drug
intervention name: 5-FU Infusion
description: 2400 mg/m2 continuous infusion over 46 hours on day 1 and 2 of a 2-week cycle.
arm group label: FOLFIRI +/- Bevacizumab
other name: fluorouracil
intervention type: Drug
intervention name: l-LV (dl-LV)
description: 200 (dl-LV: 400) mg/m2 intravenously administered over 120 minutes on day 1 of a 2-week cycle.
arm group label: FOLFIRI +/- Bevacizumab
other name: Leucovorin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ruihua Xu, MD, PhD
phone: 87343333
email: xurh@sysucc.org.cn
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Ruihua Xu
investigator title: Professor and President
mesh term: Neoplasms
mesh term: Neoplasm Metastasis
mesh term: Colorectal Neoplasms
mesh term: Gastrointestinal Neoplasms
mesh term: Digestive System Neoplasms
mesh term: Intestinal Neoplasms
mesh term: Leucovorin
mesh term: Bevacizumab
mesh term: Fluorouracil
mesh term: Irinotecan
sharing ipd: Yes
ipd info type: Study Protocol