<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/NCT02250599</url>
  </required_header>
  <id_info>
    <org_study_id>ML29153</org_study_id>
    <nct_id>NCT02250599</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of TC+AVASTIN Versus TC in Patients With Metastatic Nasopharyngeal Carcinoma</brief_title>
  <official_title>Multi-center, Randomized, Controlled, Open-label Study of Bevacizumab With Carboplatin and Paclitaxel Versus Carboplatin and Paclitaxel in Patients With Metastatic Nasopharyngeal Carcinoma</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>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The present study will be a randomized, control, multicenter phase II study of metastatic&#xD;
      nasopharyngeal carcinoma (NPC) treated with evacizumab (AVASTIN,Roch) with paclitaxel and&#xD;
      carboplatin regimen (TC+AVASTIN) or carboplatin/paclitaxel alone (TC). The population&#xD;
      consists of metastatic nasopharyngeal carcinoma (NPC) that failed the radical radiotherapy or&#xD;
      chemotherapy-naïve advanced NPC (stage IV). The effectiveness and side effects will be&#xD;
      evaluated according to RECIST 1.1 and NCI-CTC AE V4.0.TEORTC QLQ-C30 and EORTC QLQ-H&amp;N35 are&#xD;
      used to measure PRO outcome for this study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Nasopharyngeal carcinoma is vastly more common in East Asia, especially China has a high&#xD;
      incidence of it, and the number of new cases will account for more than 40% of the world&#xD;
      total . The disease involved population maybe more than 4 million in the world. More than&#xD;
      2700-3000 new nasopharyngeal carcinoma patients will be diagnosed in SUN YAT-SEN university&#xD;
      cancer center every year. It is most common in 40-50 years old adults and has been a top ten&#xD;
      (10th) malignant tumor in Chinese male which threaten human health and social economy.&#xD;
&#xD;
      Chemotherapy is the standard treatment of the advanced nasopharyngeal carcinoma.Several other&#xD;
      phase II study also confirmed the effectiveness of paclitaxel and carboplatin （TC） regimen in&#xD;
      advanced NPC, so it maybe a simple right choice.&#xD;
&#xD;
      Increasing expression of VEGF in serum associated with poor prognosis in metastatic&#xD;
      nasopharyngeal carcinoma. Agents that selectively target VEGF-A and its receptors have shown&#xD;
      significant antitumor effects in xenograft models of nasopharyngeal. Studies demonstrated&#xD;
      that bevacizumab（AVASTIN） administration with chemotherapy or chemoradiation is feasible in&#xD;
      patients with nasopharyngeal cancer. Bevacizumab can be safely combined with a range of&#xD;
      cytotoxic and other anticancer agents including TC regimen.&#xD;
&#xD;
      Evidence indicated a potential possibility that the TC+AVASTIN regimen may be superior than&#xD;
      TC regimen.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>August 2014</start_date>
  <completion_date type="Anticipated">December 2016</completion_date>
  <primary_completion_date type="Anticipated">April 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression free survival(PFS)</measure>
    <time_frame>3 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival(OS)</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response rate (ORR,CR+PR)</measure>
    <time_frame>3 years</time_frame>
    <description>Identified by investigators and independent radiologic review (IRC) respectively</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate(DCR,CR+PR+SD)</measure>
    <time_frame>3 years</time_frame>
    <description>Identified by investigators and IRC respectively</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related quality of life</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Adverse Events</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival(PFS)</measure>
    <time_frame>3 years</time_frame>
    <description>Identified by IRC</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Nasopharyngeal Neoplasms</condition>
  <arm_group>
    <arm_group_label>carboplatin and paclitaxel</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>carboplatin and paclitaxel :paclitaxel 175 mg/m2 IV and carboplatin AUC 6 IV on Day 1 of each 3-week cycle</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AVASTIN and carboplatin and paclitaxel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AVASTIN and carboplatin and paclitaxel: Bevacizumab(AVASTIN) 7.5 mg/kg intravenously (IV) infusion on Day 1 of each 3-week cycle; paclitaxel 175 mg/m2 IV and carboplatin AUC 6 IV on Day 1 of each 3-week cycle</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>Paclitaxel 175 mg/m2 IV Day 1 each 3-week cycle</description>
    <arm_group_label>AVASTIN and carboplatin and paclitaxel</arm_group_label>
    <arm_group_label>carboplatin and paclitaxel</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bevacizumab</intervention_name>
    <description>Bevacizumab 7.5 mg/kg Day 1 each 3-week cycle</description>
    <arm_group_label>AVASTIN and carboplatin and paclitaxel</arm_group_label>
    <other_name>AVASTIN</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>Carboplatin AUC 6 IV Day 1 each 3-week cycle</description>
    <arm_group_label>AVASTIN and carboplatin and paclitaxel</arm_group_label>
    <arm_group_label>carboplatin and paclitaxel</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must meet the following criteria for study entry:&#xD;
&#xD;
          -  Age ≥ 18&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0~1&#xD;
&#xD;
          -  Patients with a life expectancy&gt;12 weeks&#xD;
&#xD;
          -  Histologically proven NPC diagnosis&#xD;
&#xD;
          -  Metastatic nasopharyngeal carcinoma with evidence of unsuitable for local treatment(in&#xD;
             terms of some relevant therapy for anti-tumor like surgery, radiofrequency ablation,&#xD;
             transcatheter arterial chemoembolization(TACE) and radiotherapy(except palliative&#xD;
             radiotherapy for metastatic bone pain with appropriate radiation dosage without&#xD;
             influence to the hemogram),etc.)&#xD;
&#xD;
          -  Neoadjuvant or concurrent chemoradiotherapy was allowed, provided that the treatment&#xD;
             was completed at least 3 months before the start of study drug treatment&#xD;
&#xD;
             -≥1 measurable target based on RECIST criteria&#xD;
&#xD;
          -  Adequate bone marrow, hepatic and renal function, defined as follows within 1 weeks&#xD;
             prior to randomization&#xD;
&#xD;
          -  Patients must sign study specific informed consent prior to registration&#xD;
&#xD;
          -  Patient must have recovered (be &gt;28 days post-surgery) from the effects of surgery,&#xD;
             postoperative infection, and other complications before initial treatment with&#xD;
             bevacizumab&#xD;
&#xD;
          -  Systolic blood pressure ≤ 160 mmHg and diastolic pressure ≤ 90 mmHg within 7 days&#xD;
             prior to randomization.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior systemic treatment for metastatic nasopharyngeal carcinoma&#xD;
&#xD;
          -  Preparing for receiving local treatment for metastatic nasopharyngeal carcinoma&#xD;
             (excluding palliative irradiation to release skeletal pain)&#xD;
&#xD;
          -  Prior treatment with bevacizumab or other agents specifically targeting VEGF&#xD;
&#xD;
          -  Patients with hemorrhage tendency including acute hemorrhage of digestive tract, nasal&#xD;
             bleeding （not including nasal epistaxis), continuous hemorrhagic disease or&#xD;
             Coagulation function disorder disease. Patients are using known NSAIDS to inhibit&#xD;
             platelets.&#xD;
&#xD;
          -  Patients with gross hemoptysis or hematemesis (defined as bright red blood of 1&#xD;
             teaspoon or more or frank clots within minimal or no phlegm per coughing episode)&#xD;
             within 4 weeks prior to registration; patients with incidental blood mixed with phlegm&#xD;
             are not excluded&#xD;
&#xD;
          -  Patients receiving other experimental therapeutic cancer treatment&#xD;
&#xD;
          -  Severe, active co-morbidity, defined as follows:&#xD;
&#xD;
             i.--Unstable angina and/or congestive heart failure or vascular (e.g. aortic aneurysm&#xD;
             requiring surgical repair or peripheral thrombosis) disease requiring hospitalization&#xD;
             within the last 12 months, or other cardiac compromise (e.g. an inadequately&#xD;
             controlled cardiac arrhythmia) that in the judgment of the investigator will preclude&#xD;
             the safe administration of a study drug; Patient must not show sign of recent&#xD;
             myocardial infarction or ischemia by the findings of S-T elevations of ≥ 2mm on an EKG&#xD;
             ii.--History of arterial thromboembolic events, venous thromboembolism &gt;NCI CTCAE&#xD;
             Grade 3, transient ischemic attack (TIA), cerebral vascular accident (CVA), transmural&#xD;
             myocardial infarction (MI), or hypertensive crisis or hypertensive encephalopathy&#xD;
             iii.--History of ongoing bleeding diathesis, hemorrhagic disorder, or coagulopathy&#xD;
             iv.--Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness&#xD;
             requiring hospitalization or precluding study therapy within 30 days prior to&#xD;
             registration v.--History of abdominal fistula, gastrointestinal perforation,&#xD;
             intra-abdominal abscess, or active GI bleeding within the last 6 months prior to&#xD;
             registration; vi.--Esophageal varices, non-healing ulcer, non-healing wound, or bone&#xD;
             fracture within the last 6 months prior to registration vii.--Active, untreated&#xD;
             infection and/or acute bacterial or fungal infection uiring intravenous antibiotics at&#xD;
             the time of registration viii.--Acquired Immune Deficiency Syndrome (AIDS) based upon&#xD;
             current CDC definition; ix. Hepatic insufficiency resulting in clinical jaundice&#xD;
             and/or coagulation defects x. - Minor surgical procedure including placement of a&#xD;
             vascular access device, within 2 days of the first study treatment&#xD;
&#xD;
          -  Patients currently (within 10 days of study enrollment) taking warfarin, heparin,&#xD;
             daily treatment with aspirin (&gt; 325 mg/day), or nonsteroidal anti-inflammatory&#xD;
             medications known to inhibit platelet function; treatment with dipyramidole,&#xD;
             ticlopidine, clopidogrel, or cilostazol&#xD;
&#xD;
          -  Pregnancy or women of childbearing potential and men who are sexually active and not&#xD;
             willing/able to use medically acceptable forms of contraception;&#xD;
&#xD;
          -  Prior allergic reaction to the study drug(s) involved in this protocol&#xD;
&#xD;
          -  Contraindication to Bevacizumab&#xD;
&#xD;
          -  Patients has another cancer history （not NPC）within 5 years before 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>li zhang, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sun Yat-sen University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dongguan People's Hospital</name>
      <address>
        <city>Dongguan</city>
        <state>Guangdong</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xuefang Zhang</last_name>
      <email>674854955@qq.com</email>
    </contact>
    <investigator>
      <last_name>Chun Zhang</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Department of Medical Oncology,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>li zhang, MD</last_name>
      <phone>86-20-87343368</phone>
      <email>zhangli@sysucc.org.cn</email>
    </contact>
    <contact_backup>
      <last_name>Tao Qin</last_name>
      <phone>13570396232</phone>
      <email>tantao@sysucc.org.cn</email>
    </contact_backup>
    <investigator>
      <last_name>Yan Huang, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xuewu Huang</last_name>
      <email>doctorhxw@sina.com</email>
    </contact>
    <investigator>
      <last_name>Lizhu Lin</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Guangzhou University of Chinese Medicine</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xuewu Huang, M.D.</last_name>
      <email>doctorhxw@sina.com</email>
    </contact>
    <investigator>
      <last_name>Lizhu Lin, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Jiangmen Central Hospital</name>
      <address>
        <city>Jiangmen</city>
        <state>Guangdong</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yu Wang</last_name>
      <email>39672979@qq.com</email>
    </contact>
    <investigator>
      <last_name>Xiaofan Ding</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Shenzhen People's Hospital</name>
      <address>
        <city>Shenzhen</city>
        <state>Guangdong</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ruilian Xu</last_name>
      <email>xuruilian@126.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>The People's Hospital of Guangxi Zhuang Autonomous Region</name>
      <address>
        <city>Nanning</city>
        <state>Guangxi</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zhiyong Xu</last_name>
      <email>18978187401@189.cn</email>
    </contact>
    <investigator>
      <last_name>Guosheng Feng</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hainan General Hospital</name>
      <address>
        <city>Haikou</city>
        <state>Hainan</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yanju Chen</last_name>
      <email>cyj-0001@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2015</verification_date>
  <study_first_submitted>August 26, 2014</study_first_submitted>
  <study_first_submitted_qc>September 24, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 26, 2014</study_first_posted>
  <last_update_submitted>December 28, 2015</last_update_submitted>
  <last_update_submitted_qc>December 28, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 30, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>Li Zhang</investigator_full_name>
    <investigator_title>Profressor</investigator_title>
  </responsible_party>
  <keyword>Metastatic Nasopharyngeal Carcinoma</keyword>
  <keyword>treatment</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Nasopharyngeal Carcinoma</mesh_term>
    <mesh_term>Nasopharyngeal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Bevacizumab</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02250599
org study id: ML29153
nct id: NCT02250599
lead sponsor: 
has dmc: Yes
The present study will be a randomized, control, multicenter phase II study of metastatic
      nasopharyngeal carcinoma (NPC) treated with evacizumab (AVASTIN,Roch) with paclitaxel and
      carboplatin regimen (TC+AVASTIN) or carboplatin/paclitaxel alone (TC). The population
      consists of metastatic nasopharyngeal carcinoma (NPC) that failed the radical radiotherapy or
      chemotherapy-naïve advanced NPC (stage IV). The effectiveness and side effects will be
      evaluated according to RECIST 1.1 and NCI-CTC AE V4.0.TEORTC QLQ-C30 and EORTC QLQ-H&N35 are
      used to measure PRO outcome for this study.
Nasopharyngeal carcinoma is vastly more common in East Asia, especially China has a high
      incidence of it, and the number of new cases will account for more than 40% of the world
      total . The disease involved population maybe more than 4 million in the world. More than
      2700-3000 new nasopharyngeal carcinoma patients will be diagnosed in SUN YAT-SEN university
      cancer center every year. It is most common in 40-50 years old adults and has been a top ten
      (10th) malignant tumor in Chinese male which threaten human health and social economy.

      Chemotherapy is the standard treatment of the advanced nasopharyngeal carcinoma.Several other
      phase II study also confirmed the effectiveness of paclitaxel and carboplatin （TC） regimen in
      advanced NPC, so it maybe a simple right choice.

      Increasing expression of VEGF in serum associated with poor prognosis in metastatic
      nasopharyngeal carcinoma. Agents that selectively target VEGF-A and its receptors have shown
      significant antitumor effects in xenograft models of nasopharyngeal. Studies demonstrated
      that bevacizumab（AVASTIN） administration with chemotherapy or chemoradiation is feasible in
      patients with nasopharyngeal cancer. Bevacizumab can be safely combined with a range of
      cytotoxic and other anticancer agents including TC regimen.

      Evidence indicated a potential possibility that the TC+AVASTIN regimen may be superior than
      TC regimen.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression free survival(PFS)
time frame: 3 years
measure: Overall survival(OS)
time frame: 3 years
measure: Overall response rate (ORR,CR+PR)
time frame: 3 years
description: Identified by investigators and independent radiologic review (IRC) respectively
measure: Disease control rate(DCR,CR+PR+SD)
time frame: 3 years
description: Identified by investigators and IRC respectively
measure: Health-related quality of life
time frame: 3 years
measure: Number of Participants with Adverse Events
time frame: 3 years
measure: Progression free survival(PFS)
time frame: 3 years
description: Identified by IRC
arm group label: carboplatin and paclitaxel
arm group type: Active Comparator
description: carboplatin and paclitaxel :paclitaxel 175 mg/m2 IV and carboplatin AUC 6 IV on Day 1 of each 3-week cycle
arm group label: AVASTIN and carboplatin and paclitaxel
arm group type: Experimental
description: AVASTIN and carboplatin and paclitaxel: Bevacizumab(AVASTIN) 7.5 mg/kg intravenously (IV) infusion on Day 1 of each 3-week cycle; paclitaxel 175 mg/m2 IV and carboplatin AUC 6 IV on Day 1 of each 3-week cycle
intervention type: Drug
intervention name: Paclitaxel
description: Paclitaxel 175 mg/m2 IV Day 1 each 3-week cycle
arm group label: AVASTIN and carboplatin and paclitaxel
arm group label: carboplatin and paclitaxel
intervention type: Drug
intervention name: Bevacizumab
description: Bevacizumab 7.5 mg/kg Day 1 each 3-week cycle
arm group label: AVASTIN and carboplatin and paclitaxel
other name: AVASTIN
intervention type: Drug
intervention name: Carboplatin
description: Carboplatin AUC 6 IV Day 1 each 3-week cycle
arm group label: AVASTIN and carboplatin and paclitaxel
arm group label: carboplatin and paclitaxel
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: li zhang, MD
role: Principal Investigator
affiliation: Sun Yat-sen University
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Li Zhang
investigator title: Profressor
mesh term: Carcinoma
mesh term: Nasopharyngeal Carcinoma
mesh term: Nasopharyngeal Neoplasms
mesh term: Paclitaxel
mesh term: Bevacizumab
mesh term: Carboplatin