<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/NCT03015675</url>
  </required_header>
  <id_info>
    <org_study_id>GCV 001</org_study_id>
    <nct_id>NCT03015675</nct_id>
  </id_info>
  <brief_title>IV Ascorbic Acid in Advanced Gastric Cancer</brief_title>
  <official_title>Phase Ⅲ Study of IV Ascorbic Acid in Combination With XELOX vs Treatment With XELOX Alone as First-line Therapy for Advanced Gastric 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>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Linus Pauling and Dr Ewan Cameron have published two retrospective studies about using high&#xD;
      dose vitamin C to treat cancer patients forty years ago. Their studies have shown that high&#xD;
      dose vitamin C usage could significantly prolong overall survival of patients with advanced&#xD;
      cancer. Recently, preclinical study has shown that human colorectal cancer cells harboring&#xD;
      KRAS or BRAF mutations are selectively killed by high levels of ascorbic acid (AA). High dose&#xD;
      of AA impairs tumor growth in Apc/KRASG12D mutant mice. Previous phaseⅠclinical trials have&#xD;
      found that high dose (1.5g/kg or 90g/m2) iv AA is well tolerated in cancer patients. This&#xD;
      protocol is a phase Ⅲ, study of ascorbic acid (AA) infusions combined with treatment with&#xD;
      mFOLOX6 versus mFOLOX6 alone as first-line therapy in patients with recurrent or advanced&#xD;
      gastric cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Linus Pauling and Dr Ewan Cameron have published two retrospective studies about using high&#xD;
      dose vitamin C to treat cancer patients forty years ago. Their studies have shown that high&#xD;
      dose vitamin C usage could significantly prolong overall survival of patients with advanced&#xD;
      cancer. Recently, preclinical study has shown that human colorectal cancer cells harboring&#xD;
      KRAS or BRAF mutations are selectively killed by high levels of ascorbic acid (AA). High dose&#xD;
      of AA impairs tumor growth in Apc/KRASG12D mutant mice. Previous phaseⅠclinical trials have&#xD;
      found that high dose (1.5g/kg or 90g/m2) iv AA is well tolerated in cancer patients. This&#xD;
      protocol is a phase Ⅲ, study of ascorbic acid (AA) infusions combined with treatment with&#xD;
      mFOLOX6 versus mFOLOX6 alone as first-line therapy in patients with recurrent or advanced&#xD;
      gastric cancer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 12, 2017</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">December 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>Progression Free Survival</measure>
    <time_frame>up to 5 years</time_frame>
    <description>Time-to-event outcome measure (initial disease progression) measured in days from cycle 1 day 1 to day of first progression as defined by RECIST1.1 criteria from NCI</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>up to 5 years</time_frame>
    <description>Time to event outcome measure (death), measured in days from cycle 1 day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response Rate</measure>
    <time_frame>up to 5 years</time_frame>
    <description>To utilize CT or PET/CT scans to assess overall tumor response rate (complete and partial response) and evaluate disease progression in subjects with advanced or recurrent RAS mutant colorectal cancer treated with the combination of ascorbic acid and FOLOX/FORFIRI +/- bevacizumab versus treatment with FOLFOX/FORFIRI +/- bevacizumab alone</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Gastric Cancer</condition>
  <arm_group>
    <arm_group_label>Ascorbic Acid with mFOLFOX6 group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ascorbic Acid with mFOLFOX6 Ascorbic Acid (20g/day, D1-3) every 2 weeks&#xD;
mFOLOX6:&#xD;
Oxaliplatin 85 mg/m² d1 concurrent with&#xD;
Leucovorin 400 mg/m², followed by&#xD;
Bolus 5FU 400 mg/m² , followed by&#xD;
Infusional 5FU 2400 mg/m² over 46 hours, every 2 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>mFOLFOX6 group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>mFOLOX6:&#xD;
Oxaliplatin 85 mg/m² d1 concurrent with&#xD;
Leucovorin 400 mg/m², followed by&#xD;
Bolus 5FU 400 mg/m² , followed by&#xD;
Infusional 5FU 2400 mg/m² over 46 hours, every 2 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ascorbic acid</intervention_name>
    <description>20g/day, D1-3, every 2 weeks</description>
    <arm_group_label>Ascorbic Acid with mFOLFOX6 group</arm_group_label>
    <other_name>vitamin C</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>mFOLFOX6</intervention_name>
    <description>mFOLFOX6&#xD;
Oxaliplatin 85 mg/m² d1 concurrent with&#xD;
Leucovorin 400 mg/m², followed by&#xD;
Bolus 5FU 400 mg/m² , followed by&#xD;
Infusional 5FU 2400 mg/m² over 46 hours, every 2 weeks</description>
    <arm_group_label>Ascorbic Acid with mFOLFOX6 group</arm_group_label>
    <arm_group_label>mFOLFOX6 group</arm_group_label>
    <other_name>chemotherapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Age≥18 years, ≤75 years; Histologically proven metastatic adenocarcinoma of stomach (stage&#xD;
        4 disease), unresectable metastatic disease; G6PD status &gt; lower limit of normal; Eastern&#xD;
        Cooperative Oncology Group (ECOG) performance status 0 to 2; Life expectancy of at least 12&#xD;
        weeks; ANC ≥1,500/mm3; Hemoglobin &gt; 8g/dL; platelet ≥ 100,000/mm3; Laboratory at baseline&#xD;
        evaluation for inclusion in the study: creatinine ≤1.5X upper limit [if the creatinine is&#xD;
        elevated, but ≤1.5X the ULN, a 24 hour ;creatinine clearance will be obtained, Creatinine&#xD;
        clearance &gt; 50 mL/min (calculated according to Cockroft and Gault)]; Transaminase (AST/ALT)&#xD;
        ≤2.5X upper limit of normal and bilirubin levels ≤1.5X upper limit of normal without liver&#xD;
        metastasis; Transaminase (AST/ALT) ≤5X upper limit of normal and bilirubin levels ≤1.5X&#xD;
        upper limit of normal with liver metastasis; Women of childbearing potential will confirm a&#xD;
        negative pregnancy test and must practice effective contraception during the study; Written&#xD;
        informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Prior treatment for metastatic disease (adjuvant therapy with fluoropyrimidines&#xD;
        +/-oxaliplatin based regimens allowed if stopped 12 months prior to registration on study);&#xD;
        Surgery (excluding diagnostic biopsy) or irradiation within 3 weeks prior to study entry;&#xD;
        Administration of any investigational drug or agent/procedure, i.e. participation in&#xD;
        another trial within 4 weeks before beginning treatment; Concurrent chronic systemic immune&#xD;
        therapy, chemotherapy, radiation therapy (palliative radiation therapy allowed) or hormone&#xD;
        therapy not indicated in the study protocol; Brain metastasis (known or suspected);&#xD;
        Pregnant or lactating women; Other uncontrolled concomitant illness, including serious&#xD;
        uncontrolled intercurrent infection; Known allergy or any other adverse reaction to any of&#xD;
        the drugs or to any related compound; Previous (within 5 years) or concurrent malignancies&#xD;
        at other sites with the exception of surgically cured or adequately treated carcinoma&#xD;
        in-situ of the cervix and basal cell carcinoma of the skin; Patients who are on strong&#xD;
        inducers of CYP3A4 which include but are not limited to: Aminoglutethimide, Bexarotene,&#xD;
        Bosentan, Carbamazepine, Dexamethasone, Efavirenz, Fosphenytoin, Griseofulvin, Modafinil,&#xD;
        Nafcillin, Nevirapine, Oxcarbazepine, Phenobarbital, Phenytoin, Primidone, Rifabutin,&#xD;
        Rifampin, Rifapentine, St. John's wort; Medical, social or psychological condition which,&#xD;
        in the opinion of the investigator, would not permit the patient to complete the study or&#xD;
        sign meaningful informed consent; Organ allograft requiring immunosuppressive therapy;&#xD;
        Patients with HIV infection&#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>Rui-hua Xu, MD.,PhD.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sun Yat-sen University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Feng Wang, MD.,PhD.</last_name>
    <phone>+862087343795</phone>
    <email>wangfeng@sysucc.org.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>Medical 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>Feng Wang, M.D,Ph.D</last_name>
      <phone>86-18620880867</phone>
      <email>wangfeng@sysucc.org.cn</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>January 8, 2017</study_first_submitted>
  <study_first_submitted_qc>January 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 10, 2017</study_first_posted>
  <last_update_submitted>May 16, 2017</last_update_submitted>
  <last_update_submitted_qc>May 16, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 18, 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>Clinical Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stomach Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ascorbic Acid</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </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/NCT03015675
org study id: GCV 001
nct id: NCT03015675
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Linus Pauling and Dr Ewan Cameron have published two retrospective studies about using high
      dose vitamin C to treat cancer patients forty years ago. Their studies have shown that high
      dose vitamin C usage could significantly prolong overall survival of patients with advanced
      cancer. Recently, preclinical study has shown that human colorectal cancer cells harboring
      KRAS or BRAF mutations are selectively killed by high levels of ascorbic acid (AA). High dose
      of AA impairs tumor growth in Apc/KRASG12D mutant mice. Previous phaseⅠclinical trials have
      found that high dose (1.5g/kg or 90g/m2) iv AA is well tolerated in cancer patients. This
      protocol is a phase Ⅲ, study of ascorbic acid (AA) infusions combined with treatment with
      mFOLOX6 versus mFOLOX6 alone as first-line therapy in patients with recurrent or advanced
      gastric cancer.
Linus Pauling and Dr Ewan Cameron have published two retrospective studies about using high
      dose vitamin C to treat cancer patients forty years ago. Their studies have shown that high
      dose vitamin C usage could significantly prolong overall survival of patients with advanced
      cancer. Recently, preclinical study has shown that human colorectal cancer cells harboring
      KRAS or BRAF mutations are selectively killed by high levels of ascorbic acid (AA). High dose
      of AA impairs tumor growth in Apc/KRASG12D mutant mice. Previous phaseⅠclinical trials have
      found that high dose (1.5g/kg or 90g/m2) iv AA is well tolerated in cancer patients. This
      protocol is a phase Ⅲ, study of ascorbic acid (AA) infusions combined with treatment with
      mFOLOX6 versus mFOLOX6 alone as first-line therapy in patients with recurrent or advanced
      gastric cancer.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression Free Survival
time frame: up to 5 years
description: Time-to-event outcome measure (initial disease progression) measured in days from cycle 1 day 1 to day of first progression as defined by RECIST1.1 criteria from NCI
measure: Overall Survival
time frame: up to 5 years
description: Time to event outcome measure (death), measured in days from cycle 1 day 1
measure: Response Rate
time frame: up to 5 years
description: To utilize CT or PET/CT scans to assess overall tumor response rate (complete and partial response) and evaluate disease progression in subjects with advanced or recurrent RAS mutant colorectal cancer treated with the combination of ascorbic acid and FOLOX/FORFIRI +/- bevacizumab versus treatment with FOLFOX/FORFIRI +/- bevacizumab alone
arm group label: Ascorbic Acid with mFOLFOX6 group
arm group type: Experimental
description: Ascorbic Acid with mFOLFOX6 Ascorbic Acid (20g/day, D1-3) every 2 weeks
mFOLOX6:
Oxaliplatin 85 mg/m² d1 concurrent with
Leucovorin 400 mg/m², followed by
Bolus 5FU 400 mg/m² , followed by
Infusional 5FU 2400 mg/m² over 46 hours, every 2 weeks
arm group label: mFOLFOX6 group
arm group type: Active Comparator
description: mFOLOX6:
Oxaliplatin 85 mg/m² d1 concurrent with
Leucovorin 400 mg/m², followed by
Bolus 5FU 400 mg/m² , followed by
Infusional 5FU 2400 mg/m² over 46 hours, every 2 weeks
intervention type: Drug
intervention name: ascorbic acid
description: 20g/day, D1-3, every 2 weeks
arm group label: Ascorbic Acid with mFOLFOX6 group
other name: vitamin C
intervention type: Drug
intervention name: mFOLFOX6
description: mFOLFOX6
Oxaliplatin 85 mg/m² d1 concurrent with
Leucovorin 400 mg/m², followed by
Bolus 5FU 400 mg/m² , followed by
Infusional 5FU 2400 mg/m² over 46 hours, every 2 weeks
arm group label: Ascorbic Acid with mFOLFOX6 group
arm group label: mFOLFOX6 group
other name: chemotherapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Rui-hua Xu, MD.,PhD.
role: Principal Investigator
affiliation: Sun Yat-sen University
last name: Feng Wang, MD.,PhD.
phone: +862087343795
email: wangfeng@sysucc.org.cn
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Ruihua Xu
investigator title: Clinical Professor
mesh term: Stomach Neoplasms
mesh term: Ascorbic Acid
sharing ipd: Undecided