<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/NCT04472403</url>
  </required_header>
  <id_info>
    <org_study_id>B2019-201-01</org_study_id>
    <nct_id>NCT04472403</nct_id>
  </id_info>
  <brief_title>Platinum Plus Low-dose Long-term Continuous Intravenous Infused 5-Fluorouracil in Metastatic Nasopharyngeal Carcinoma</brief_title>
  <official_title>Efficacy and Safety of Platinum Plus Continuous Intravenous Infused 5-Fluorouracil With Low Dose and Long Term Versus Other Platinum-Based Chemotherapy in Metastatic Nasopharyngeal Carcinoma: A Case-Cohort Study</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>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The treatment of distant metastasis is a key challenge for nasopharyngeal carcinoma because&#xD;
      of poor outcomes, among which, chemotherapy is the cornerstone. However, many studies&#xD;
      reported the use of different chemotherapy regimens to prolong the survival of metastatic&#xD;
      nasopharyngeal carcinoma, while few of them focused on how to reduce the side effects of&#xD;
      chemotherapy or improve the life quality of patients. Thus, we sought to find an efficient&#xD;
      chemotherapy regimen with high tolerance according to the characteristics of chemotherapy&#xD;
      drugs, that is, to explore the efficacy and safety of platinum plus 5-fluorouracil with&#xD;
      continuous intravenous infusion at a low dose for a long term.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Nasopharyngeal carcinoma (NPC) is a malignant tumor of the nasopharyngeal epithelium with&#xD;
      high sensitivity to ionizing radiation. With the use of intensive chemoradiotherapy,&#xD;
      excellent treatment outcomes can be achieved for local control, but disease failure was&#xD;
      observed in approximately 20% of patients. Moreover, approximately 10% of newly diagnosed&#xD;
      patients diagnosed with metastasis, resulting in about 30% of NPC patients will present with&#xD;
      either synchronous or metachronous metastasis in total.&#xD;
&#xD;
      Chemotherapy is the cornerstone of the treatment of metastatic NPC. Many studies were aimed&#xD;
      at the systemic treatment of metastatic NPC, but most of them were retrospective studies or&#xD;
      phase II trials with small samples. The outcome of metastatic NPC is poor with a median OS of&#xD;
      about 20 months. Platinum-containing doublet chemotherapy is generally regarded as the&#xD;
      standard treatment for metastatic NPC. After a multicenter phase III randomized clinical&#xD;
      trial was published in 2016, gemcitabine plus cisplatin is recommended, however, less than&#xD;
      60% of patients could complete the treatment in the trail. Finding a proper regimen with&#xD;
      promising efficacy results as well as high tolerance is still a big challenge.&#xD;
&#xD;
      Cisplatin plus 5-fluorouracil (PF) is a classical regimen widely used in metastatic NPC. The&#xD;
      continuous infusion of 5-fluorouracil with low dose was investigated in esophagus carcinoma,&#xD;
      rectal carcinoma and prostate carcinoma with encouraging outcome and acceptable toxicity.&#xD;
      Whereas, data of platinum-containing chemotherapy with low-dose continuous infused&#xD;
      5-fluorouracil in metastatic NPC was absent. In this study, we aimed to investigate the&#xD;
      antitumor activity of platinum plus low-dose long-term continuous intravenous infused&#xD;
      5-fluorouracil (PFLL).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 26, 2019</start_date>
  <completion_date type="Anticipated">December 2020</completion_date>
  <primary_completion_date type="Anticipated">August 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>5-year overall survival</measure>
    <time_frame>5 years after diagnosis of metastasis</time_frame>
    <description>The period until death is detected.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>5-year subsequent-line treatment-free survival</measure>
    <time_frame>5 years after the start of the first-line treatment</time_frame>
    <description>The period until earliest of the start date of subsequent-line treatment or death is detected.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>5-year survival without symptoms and toxicity</measure>
    <time_frame>5 years after diagnosis of metastasis</time_frame>
    <description>The period until any events (death or disease progression or ≥grade 3 chemotherapy-related haematological toxicity) is detected.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Haematological toxicity</measure>
    <time_frame>From the start of the first-line treatment, evaluation was performed every cycle during the treatment and then every 3-6 months after the completion of the treatment, up to the start of subsequent-line treatment or death or 5 years.</time_frame>
    <description>The incidence of myelosuppression</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">2000</enrollment>
  <condition>Nasopharyngeal Carcinoma</condition>
  <condition>Metastasis</condition>
  <condition>Chemotherapy</condition>
  <condition>Survival</condition>
  <arm_group>
    <arm_group_label>PFLL Group</arm_group_label>
    <description>Patients were treated with PFLL regimen: 5-fluorouracil intravenous infusion at 200mg/m2/d for 30 continuous days and intravenous infusion of platinum (cisplatin 70 mg/m2 or nedaplatin 80/m2 or lobaplatin 30 mg/m2) on day 1 and day 28, every 60 days.&#xD;
Local treatment, molecular-targeted or immune checkpoint therapy, and supportive treatment were allowed.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-PFLL Group</arm_group_label>
    <description>Patients were treated with other platinum-based chemotherapy every 21 days including:&#xD;
PF regimen: 5-fluorouracil at a dose of 1,000 mg/m2 daily by continuous intravenous infusion on days 1-4 and intravenous infusion of cisplatin at a dose of 80 mg/m2 on day 1.&#xD;
GP regimen: gemcitabine at a dose of 1,000 mg/m2 by intravenous infusion on days 1, 8, and intravenous infusion of cisplatin at a dose of 80 mg/m2 on day 1.&#xD;
TP regimen: paclitaxel intravenous infusion at a dose of 175 mg/m2 or docetaxel at a dose of 75 mg/m2 on day 1 and intravenous infusion of cisplatin at a dose of 75 mg/m2 on day 1.&#xD;
TPF regimen: paclitaxel intravenous infusion at a dose of 175 mg/m2 or docetaxel at a dose of 75 mg/m2 on day 1; cisplatin intravenous infusion at a dose of 75 mg/m2 on day 1 and continuous intravenous infusion of 5-FU at a dose of 750 mg/m2 daily on days 1-5.&#xD;
Local treatment, molecular-targeted or immune checkpoint therapy, and supportive treatment were allowed.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        All patients involved in our study were patients who had histologically or cytologically&#xD;
        confirmed NPC with diagnosed distant metastasis during 2006-2017 and receiving treatment in&#xD;
        our hospital.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Nasopharyngeal carcinoma diagnosed by pathology or cytology&#xD;
&#xD;
          -  Distant metastasis confirmed by Radiographic assessments or pathology.&#xD;
&#xD;
          -  Patients ever received systemic chemotherapy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &lt;18 or &gt;70 years old&#xD;
&#xD;
          -  Pathologic type unknown or except type I-III of World Health Organization&#xD;
             classification&#xD;
&#xD;
          -  Never underwent platinum-based chemotherapy&#xD;
&#xD;
          -  Lack of information about T classification and N classification when metastasis&#xD;
&#xD;
          -  Lost follow-up within one month from the start of treatment for metastasis&#xD;
&#xD;
          -  Without other malignances&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yun-fei Xia, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sun Yat-sen University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Yun-fei Xia, MD</last_name>
    <phone>+8613602805461</phone>
    <email>xiayf@sysucc.org.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Shuo-han Zheng, MD</last_name>
    <phone>+8613826478924</phone>
    <email>zhengsh1@sysucc.org.cn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department of Radiation Oncology, Sun Yat-Sen University Cancer Center</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yun-fei Xia, MD</last_name>
      <phone>+8613602805461</phone>
      <email>xiayf@sysucc.org.cn</email>
    </contact>
    <contact_backup>
      <last_name>Shuo-han Zheng, MD</last_name>
      <phone>+8613826478924</phone>
      <email>zhengsh1@sysucc.org.cn</email>
    </contact_backup>
    <investigator>
      <last_name>Yun-fei Xia, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Shuo-han Zheng, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 11, 2020</study_first_submitted>
  <study_first_submitted_qc>July 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 15, 2020</study_first_posted>
  <last_update_submitted>July 16, 2020</last_update_submitted>
  <last_update_submitted_qc>July 16, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 20, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>Yun-fei Xia</investigator_full_name>
    <investigator_title>Department of Radiation Oncology, Sun Yat-sen University Cancer Center</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Nasopharyngeal Carcinoma</mesh_term>
  </condition_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/NCT04472403
org study id: B2019-201-01
nct id: NCT04472403
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The treatment of distant metastasis is a key challenge for nasopharyngeal carcinoma because
      of poor outcomes, among which, chemotherapy is the cornerstone. However, many studies
      reported the use of different chemotherapy regimens to prolong the survival of metastatic
      nasopharyngeal carcinoma, while few of them focused on how to reduce the side effects of
      chemotherapy or improve the life quality of patients. Thus, we sought to find an efficient
      chemotherapy regimen with high tolerance according to the characteristics of chemotherapy
      drugs, that is, to explore the efficacy and safety of platinum plus 5-fluorouracil with
      continuous intravenous infusion at a low dose for a long term.
Nasopharyngeal carcinoma (NPC) is a malignant tumor of the nasopharyngeal epithelium with
      high sensitivity to ionizing radiation. With the use of intensive chemoradiotherapy,
      excellent treatment outcomes can be achieved for local control, but disease failure was
      observed in approximately 20% of patients. Moreover, approximately 10% of newly diagnosed
      patients diagnosed with metastasis, resulting in about 30% of NPC patients will present with
      either synchronous or metachronous metastasis in total.

      Chemotherapy is the cornerstone of the treatment of metastatic NPC. Many studies were aimed
      at the systemic treatment of metastatic NPC, but most of them were retrospective studies or
      phase II trials with small samples. The outcome of metastatic NPC is poor with a median OS of
      about 20 months. Platinum-containing doublet chemotherapy is generally regarded as the
      standard treatment for metastatic NPC. After a multicenter phase III randomized clinical
      trial was published in 2016, gemcitabine plus cisplatin is recommended, however, less than
      60% of patients could complete the treatment in the trail. Finding a proper regimen with
      promising efficacy results as well as high tolerance is still a big challenge.

      Cisplatin plus 5-fluorouracil (PF) is a classical regimen widely used in metastatic NPC. The
      continuous infusion of 5-fluorouracil with low dose was investigated in esophagus carcinoma,
      rectal carcinoma and prostate carcinoma with encouraging outcome and acceptable toxicity.
      Whereas, data of platinum-containing chemotherapy with low-dose continuous infused
      5-fluorouracil in metastatic NPC was absent. In this study, we aimed to investigate the
      antitumor activity of platinum plus low-dose long-term continuous intravenous infused
      5-fluorouracil (PFLL).
observational model: Cohort
time perspective: Retrospective
measure: 5-year overall survival
time frame: 5 years after diagnosis of metastasis
description: The period until death is detected.
measure: 5-year subsequent-line treatment-free survival
time frame: 5 years after the start of the first-line treatment
description: The period until earliest of the start date of subsequent-line treatment or death is detected.
measure: 5-year survival without symptoms and toxicity
time frame: 5 years after diagnosis of metastasis
description: The period until any events (death or disease progression or ≥grade 3 chemotherapy-related haematological toxicity) is detected.
measure: Haematological toxicity
time frame: From the start of the first-line treatment, evaluation was performed every cycle during the treatment and then every 3-6 months after the completion of the treatment, up to the start of subsequent-line treatment or death or 5 years.
description: The incidence of myelosuppression
arm group label: PFLL Group
description: Patients were treated with PFLL regimen: 5-fluorouracil intravenous infusion at 200mg/m2/d for 30 continuous days and intravenous infusion of platinum (cisplatin 70 mg/m2 or nedaplatin 80/m2 or lobaplatin 30 mg/m2) on day 1 and day 28, every 60 days.
Local treatment, molecular-targeted or immune checkpoint therapy, and supportive treatment were allowed.
arm group label: Non-PFLL Group
description: Patients were treated with other platinum-based chemotherapy every 21 days including:
PF regimen: 5-fluorouracil at a dose of 1,000 mg/m2 daily by continuous intravenous infusion on days 1-4 and intravenous infusion of cisplatin at a dose of 80 mg/m2 on day 1.
GP regimen: gemcitabine at a dose of 1,000 mg/m2 by intravenous infusion on days 1, 8, and intravenous infusion of cisplatin at a dose of 80 mg/m2 on day 1.
TP regimen: paclitaxel intravenous infusion at a dose of 175 mg/m2 or docetaxel at a dose of 75 mg/m2 on day 1 and intravenous infusion of cisplatin at a dose of 75 mg/m2 on day 1.
TPF regimen: paclitaxel intravenous infusion at a dose of 175 mg/m2 or docetaxel at a dose of 75 mg/m2 on day 1; cisplatin intravenous infusion at a dose of 75 mg/m2 on day 1 and continuous intravenous infusion of 5-FU at a dose of 750 mg/m2 daily on days 1-5.
Local treatment, molecular-targeted or immune checkpoint therapy, and supportive treatment were allowed.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Yun-fei Xia, MD
role: Principal Investigator
affiliation: Sun Yat-sen University
last name: Yun-fei Xia, MD
phone: +8613602805461
email: xiayf@sysucc.org.cn
last name: Shuo-han Zheng, MD
phone: +8613826478924
email: zhengsh1@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: Yun-fei Xia
investigator title: Department of Radiation Oncology, Sun Yat-sen University Cancer Center
mesh term: Carcinoma
mesh term: Nasopharyngeal Carcinoma