<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/NCT03799094</url>
  </required_header>
  <id_info>
    <org_study_id>2/2018-19</org_study_id>
    <nct_id>NCT03799094</nct_id>
  </id_info>
  <brief_title>Vitamin C and Tyrosine Kinase Inhibitor in Lung Cancer Patients With Epidermal Growth Factor Receptor Mutations</brief_title>
  <official_title>Clinical Outcomes of Intravenous Vitamin C Synergy With Tyrosine Kinase Inhibitor in Lung Adenocarcinoma Patients With Epidermal Growth Factor Receptor Mutations</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Clifford Hospital, Guangzhou, China</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Clifford Hospital, Guangzhou, China</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This trial was to explore whether intravenous vitamin C can prolong resistance time of&#xD;
      Tyrosine Kinase Inhibitor(TKI) on lung adenocarcinoma patients with Epidermal Growth Factor&#xD;
      Receptor(EGFR) mutations, and can benefit NSCLC patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The effects of vitamin C in combination with tyrosine kinase inhibitor on tumor size, tumor&#xD;
      markers, inflammatory factor levels, quality of life, duration of resistance,&#xD;
      progression-free survival, and overall survival time were evaluated.&#xD;
&#xD;
      This trial is a low risk treatment, and has developed the appropriate safety measures and&#xD;
      contingency plans to ensure patients' safety in the whole process.&#xD;
&#xD;
      Patients will be followed up after the end of the trial, and follow-up observations will be&#xD;
      performed every month during the first year. Followed every 3 months in the second year for 3&#xD;
      years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">December 5, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2020</primary_completion_date>
  <phase>Phase 1/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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>From the start date of treatment until the date of first documented progression or death, assessed up to 2 years</time_frame>
    <description>From the start of treatment until the patient has tumor progression or death</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From the start date of treatment until the date of death from any cause, assessed up to 2 years.</time_frame>
    <description>The length of time from the start of treatment for a disease until death</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Changes in Health Related Quality of Life: European Organisation for Research and Treatment of Cancer(EORTC) quality of life questionnaire(QLQ)-C30</measure>
    <time_frame>From the start date of treatment until the date of first documented progression or death, assessed up to 2 years</time_frame>
    <description>Using QLQ-C30: Function subscales, (include physical, role, emotional, cognitive, social, global) (averaged, 0-100, higher value represent a better outcome); Symptoms subscales (include fatigue, nausea, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea) (averaged, 0-100, lower value represent a better outcome). Given at basal, 1, 2, 3, 6, 12 months.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Carcinoma, Non-Small-Cell Lung</condition>
  <arm_group>
    <arm_group_label>Experimental group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>75 patients received a weekly intravenous Vitamin C injection (dose: 30 g / time, once a week, treatment termination when the disease progress is confirmed) in combination with daily taking tyrosine kinase inhibitor.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>75 patients received tyrosine kinase inhibitor daily. (dose: Osimertinib 80 mg/d, or Tarceva 150 mg/d, or Iressa 0.25 g/d.)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vitamin C</intervention_name>
    <description>Participants will receive intravenous vitamin C therapy at the indicated dose.</description>
    <arm_group_label>Experimental group</arm_group_label>
    <other_name>Sodium Ascorbate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tyrosine kinase inhibitor</intervention_name>
    <description>Participants will receive Tyrosine kinase inhibitor therapy in cycles: continuous treatment at the indicated dose.</description>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_label>Experimental group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Primary non-small cell lung cancer (adenocarcinoma) with EGFR mutations on exons 19&#xD;
             and 21.&#xD;
&#xD;
          -  18 years old to 75 years old.&#xD;
&#xD;
          -  During the trial, patients were prescribed TKI drugs(received initial treatment within&#xD;
             2 months, or change medication within 2 months) and did not receive chemotherapy or&#xD;
             radiotherapy at the same time.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status are 0 to 2.&#xD;
&#xD;
          -  Expected survival over 3 months.&#xD;
&#xD;
          -  Household registration is Guangdong Province.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Co-morbid conditions that affect survival: end stage congestive heart failure,&#xD;
             unstable angina, myocardial infarction (within the past 6 weeks), and uncontrolled&#xD;
             blood sugars of greater than 300 mg/dL, known chronic active hepatitis or cirrhosis.&#xD;
&#xD;
          -  Glucose-6-phosphate dehydrogenase deficiency (G6PD) (a relative contraindication).&#xD;
&#xD;
          -  Patients who are allergic to vitamin C.&#xD;
&#xD;
          -  Patients with HIV and other infectious diseases.&#xD;
&#xD;
          -  Patients who are taking anticoagulants and have coagulopathy;&#xD;
&#xD;
          -  Combine dysfunction of important organs such as heart, lung, liver and kidney;&#xD;
&#xD;
          -  Patients with impaired renal function (serum creatinine content &gt; 1.2 mg/dL)&#xD;
&#xD;
          -  Compromised liver function with evidence of Serum total bilirubin content, Serum&#xD;
             alanine aminotransferase(ALT) and aspartate transaminase(AST)&gt; 2 times normal&#xD;
             reference value.&#xD;
&#xD;
          -  Pregnant or lactating female.&#xD;
&#xD;
          -  Smoking and alcohol abuse patients;&#xD;
&#xD;
          -  Anti-infective treatment is required for systemic or localized serious infections;&#xD;
&#xD;
          -  Patients with hyperuricacidemia (normal: 91-456 μmol / 24h (8-40mg / 24h));&#xD;
&#xD;
          -  Wilson's disease.&#xD;
&#xD;
          -  Evidence of significant psychiatric disorder by history or examination that would&#xD;
             prevent completion of the study or preclude informed consent.&#xD;
&#xD;
          -  Any condition that impairs the patients' ability to swallow, which impairs drug&#xD;
             absorption or drug kinetic parameters, including any kind of gastrointestinal&#xD;
             resection or surgery;&#xD;
&#xD;
          -  History of surgery of visceral organs within 6 weeks before the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Junwen Ou, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Clifford Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Junwen Ou, PhD</last_name>
    <phone>86-13556021810</phone>
    <email>oujunwen66@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Clifford Hospital</name>
      <address>
        <city>Guangzhou</city>
        <zip>511495</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Junwen Ou, PhD</last_name>
      <phone>86-13556021810</phone>
      <email>oujunwen66@163.com</email>
    </contact>
    <investigator>
      <last_name>Junwen Ou, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 2, 2019</study_first_submitted>
  <study_first_submitted_qc>January 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 10, 2019</study_first_posted>
  <last_update_submitted>January 7, 2019</last_update_submitted>
  <last_update_submitted_qc>January 7, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 10, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>tyrosine kinase inhibitor</keyword>
  <keyword>Vitamin C</keyword>
  <keyword>non-small cell lung cancer</keyword>
  <keyword>progression-free survival</keyword>
  <keyword>overall survival</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ascorbic Acid</mesh_term>
    <mesh_term>Tyrosine Protein Kinase Inhibitors</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 14, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/94/NCT03799094/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 14, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/94/NCT03799094/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03799094
org study id: 2/2018-19
nct id: NCT03799094
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This trial was to explore whether intravenous vitamin C can prolong resistance time of
      Tyrosine Kinase Inhibitor(TKI) on lung adenocarcinoma patients with Epidermal Growth Factor
      Receptor(EGFR) mutations, and can benefit NSCLC patients.
The effects of vitamin C in combination with tyrosine kinase inhibitor on tumor size, tumor
      markers, inflammatory factor levels, quality of life, duration of resistance,
      progression-free survival, and overall survival time were evaluated.

      This trial is a low risk treatment, and has developed the appropriate safety measures and
      contingency plans to ensure patients' safety in the whole process.

      Patients will be followed up after the end of the trial, and follow-up observations will be
      performed every month during the first year. Followed every 3 months in the second year for 3
      years.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Progression free survival
time frame: From the start date of treatment until the date of first documented progression or death, assessed up to 2 years
description: From the start of treatment until the patient has tumor progression or death
measure: Overall survival
time frame: From the start date of treatment until the date of death from any cause, assessed up to 2 years.
description: The length of time from the start of treatment for a disease until death
measure: Changes in Health Related Quality of Life: European Organisation for Research and Treatment of Cancer(EORTC) quality of life questionnaire(QLQ)-C30
time frame: From the start date of treatment until the date of first documented progression or death, assessed up to 2 years
description: Using QLQ-C30: Function subscales, (include physical, role, emotional, cognitive, social, global) (averaged, 0-100, higher value represent a better outcome); Symptoms subscales (include fatigue, nausea, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea) (averaged, 0-100, lower value represent a better outcome). Given at basal, 1, 2, 3, 6, 12 months.
arm group label: Experimental group
arm group type: Experimental
description: 75 patients received a weekly intravenous Vitamin C injection (dose: 30 g / time, once a week, treatment termination when the disease progress is confirmed) in combination with daily taking tyrosine kinase inhibitor.
arm group label: Control group
arm group type: Experimental
description: 75 patients received tyrosine kinase inhibitor daily. (dose: Osimertinib 80 mg/d, or Tarceva 150 mg/d, or Iressa 0.25 g/d.)
intervention type: Drug
intervention name: Vitamin C
description: Participants will receive intravenous vitamin C therapy at the indicated dose.
arm group label: Experimental group
other name: Sodium Ascorbate
intervention type: Drug
intervention name: Tyrosine kinase inhibitor
description: Participants will receive Tyrosine kinase inhibitor therapy in cycles: continuous treatment at the indicated dose.
arm group label: Control group
arm group label: Experimental group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Junwen Ou, PhD
role: Study Chair
affiliation: Clifford Hospital
last name: Junwen Ou, PhD
phone: 86-13556021810
email: oujunwen66@163.com
facility: 
status: Recruiting
contact: 
investigator: 
country: China
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Ascorbic Acid
mesh term: Tyrosine Protein Kinase Inhibitors
provided document: 
provided document: 