<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/NCT03797443</url>
  </required_header>
  <id_info>
    <org_study_id>PAN-VITC</org_study_id>
    <nct_id>NCT03797443</nct_id>
  </id_info>
  <brief_title>High Dose Ascorbic Acid (AA) + Nanoparticle Paclitaxel Protein Bound + Cisplatin + Gemcitabine (AA NABPLAGEM) in Patients Who Have Metastatic Pancreatic Cancer</brief_title>
  <official_title>Phase IB/II Trial of High Dose Ascorbic Acid (AA) + Nanoparticle Paclitaxel Protein Bound + Cisplatin + Gemcitabine (AA NABPLAGEM) in Patients Who Have Had No Prior Therapy for Their Metastatic Pancreatic Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Piedmont Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cancer Research UK</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Stand Up To Cancer</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Lustgarten Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Destroy Pancreatic Cancer</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Translational Genomics Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Piedmont Cancer Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to see if a combination of paclitaxel protein bound (also known&#xD;
      as nab-paclitaxel), gemcitabine, and cisplatin when given with high dose Ascorbic Acid will&#xD;
      be safe and effective in individuals with untreated metastatic pancreatic cancer.&#xD;
&#xD;
      Vitamin C is a nutrient found in food and dietary supplements. It protects cells and also&#xD;
      plays a key role in making collagen (which provides strength and structure to skin, bones,&#xD;
      tissues and tendons). High-dose vitamin C may be given by intravenous (IV) infusion (through&#xD;
      a vein into the bloodstream) or orally (taken by mouth). When taken by intravenous infusion,&#xD;
      vitamin C can reach much higher levels in the blood than when the same amount is taken by&#xD;
      mouth. Some human studies of high-dose IV vitamin C in patients with cancer have shown&#xD;
      improved quality of life, as well as improvements in physical, mental, and emotional&#xD;
      functions, symptoms of fatigue, nausea and vomiting, pain, and appetite loss. Intravenous&#xD;
      high-dose ascorbic acid has caused very few side effects in clinical trials.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Regulatory Review needed&#xD;
  </why_stopped>
  <start_date type="Actual">January 1, 2019</start_date>
  <completion_date type="Anticipated">December 2022</completion_date>
  <primary_completion_date type="Anticipated">January 2022</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>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Ascorbic Acid Paclitaxel Protein Bound Cisplatin Gemcitabine</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Tolerated Dose</measure>
    <time_frame>approx 63 days</time_frame>
    <description>To determine the maximum tolerated dose (MTD) of high dose ascorbic acid (AA) with triple therapy of nanoparticle paclitaxel protein bound+ cisplatin + gemcitabine (NABPLAGEM) in patients with advanced stage IV metastatic pancreatic cancer</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Disease control rate (CR+PR+SD x18 weeks)</measure>
    <time_frame>approx 63 days</time_frame>
    <description>To determine the preliminary efficacy (Disease control rate of CR+ PR+SD X 18 weeks) of the combination of high dose ascorbic acid (AA) at MTD with triple therapy of nanoparticle albumin- bound paclitaxel + cisplatin + gemcitabine (NABPLAGEM) in patients with advanced stage IV metastatic pancreatic cancer.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of Treatment</measure>
    <time_frame>63 days</time_frame>
    <description>Lab testing will be completed to evaluate standard of care labs for subject safety</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of patients who normalize their CA19-9</measure>
    <time_frame>63 days</time_frame>
    <description>Lab testing will be completed to evaluate normalization of CA19-19</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>12 weeks</time_frame>
    <description>Telephone followup will be conducted every 12 weeks from the last dose of treatment to determine survival status</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free</measure>
    <time_frame>approximately 12 weeks from last study treatment ]</time_frame>
    <description>Telephone followup will be conducted every 12 weeks from the last dose of treatment to determine status of disease progression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in patient's self-reported quality of life</measure>
    <time_frame>63 days</time_frame>
    <description>Changes in patient's self-reported quality of life will be determined by administering the MD Anderson Symptom Inventory for Gastrointestinal Cancer (MDASI-GI) to assess the severity of multiple gastrointestinal cancer-related syymptoms and the impact of these symptoms of daily functiong.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in patient's self-reported pain levels</measure>
    <time_frame>63 days</time_frame>
    <description>Changes in patient's self-reported pain levels will be determined by administering the Brief Pain Inventory (BPI) to assess the severity of pain and the impact of pain on daily functions.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Metastatic Pancreatic Cancer</condition>
  <arm_group>
    <arm_group_label>AA NABPLAGEM</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ascorbic Acid Paclitaxel protein-bound cisplatin gemcitabine</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ascorbic Acid</intervention_name>
    <description>Four escalating dose levels are planned in order to determine the MTD for Phase II&#xD;
The dose level for Phase II patients will be determined following completion of the Phase 1b study based on response from 3-6 patients receiving the designated dose level of ascorbic acid.</description>
    <arm_group_label>AA NABPLAGEM</arm_group_label>
    <other_name>Vitamin C</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>nab paclitaxel</intervention_name>
    <description>30 minute IV infusions on days 1 and 8 repeated every 21 days, followed by Cisplatin</description>
    <arm_group_label>AA NABPLAGEM</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>60minute IV infusion on days 1 and 8 repeated every 21 days followed by Gemcitabine</description>
    <arm_group_label>AA NABPLAGEM</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine</intervention_name>
    <description>30 minute IV infusion on days 1 and 8 repeated every 21 days</description>
    <arm_group_label>AA NABPLAGEM</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Be willing and able to provide written informed consent/assent for the trial.&#xD;
&#xD;
          -  Be ≥ 18 years of age on day of signing informed consent.&#xD;
&#xD;
          -  Histologically or cytologically confirmed metastatic pancreatic adenocarcinoma (with&#xD;
             measurable disease according to RECIST 1.1)&#xD;
&#xD;
          -  Have a performance status of 0 or 1 on the ECOG performance scale.&#xD;
&#xD;
          -  Demonstrate adequate organ function as defined below in Table 4, all screening labs&#xD;
             should be performed within 21 days of treatment initiation.&#xD;
&#xD;
          -  Female participants of childbearing potential should have a negative serum pregnancy&#xD;
             test within 72 hours prior to receiving first dose of study medication.&#xD;
&#xD;
          -  Female participants of childbearing potential must be willing to use adequate method&#xD;
             of contraception (as outlined in section 4.4.2) for the duration of the trial through&#xD;
             one month after the last dose of trial treatment.&#xD;
&#xD;
          -  Male participants must agree to use adequate contraception (as outlined in section&#xD;
             4.4.2) for the duration of the trial through one month after the last dose of trial&#xD;
             treatment. Note: Abstinence is acceptable if this is the usual lifestyle and preferred&#xD;
             contraception for the participant.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients must have received no previous radiotherapy, surgery, chemotherapy or&#xD;
             investigational therapy for the treatment of metastatic disease. Prior treatments in&#xD;
             the adjuvant setting with gemcitabine and/or 5-FU or gemcitabine administered as a&#xD;
             radiation sensitizer are allowed, provided at least 6 months have elapsed since&#xD;
             completion of the last dose and no lingering toxicities are present.&#xD;
&#xD;
          -  Palliative surgery and/or radiation treatment less than 4 weeks prior to initiation of&#xD;
             study treatment.&#xD;
&#xD;
          -  Exposure to any investigational agent within 4 weeks prior to initiation of study&#xD;
             treatment.&#xD;
&#xD;
          -  Patients who need constant use of finger stick blood glucose monitoring for tight&#xD;
             control of their diabetes being that the ascorbic acid causes false low readings of&#xD;
             glucose via that technology (Vasudevan and Hirsch 2014) 39&#xD;
&#xD;
          -  Any person with a G6PD deficiency&#xD;
&#xD;
          -  History of renal oxalate stones (if type of stone is unknown, need to assess urine&#xD;
             oxalates level if &gt;60mg/dL, then patient is not eligible for the study)&#xD;
&#xD;
          -  Patient is taking acetaminophen at any dose or any medication that contains&#xD;
             acetaminophen within 72 hours of first dose of ascorbic acid&#xD;
&#xD;
          -  Hypersensitivity to any of the agents proposed for treatment.&#xD;
&#xD;
          -  Has a known additional malignancy that is progressing or requires active treatment.&#xD;
             Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the&#xD;
             skin that has undergone potentially curative therapy or in situ cervical cancer.&#xD;
&#xD;
          -  Has known active central nervous system (CNS) metastases and/or carcinomatous&#xD;
             meningitis. Patients with previously treated brain metastases may participate provided&#xD;
             they are stable (without evidence of progression by imaging for at least four weeks&#xD;
             prior to the first dose of trial treatment and any neurologic symptoms have returned&#xD;
             to baseline), have no evidence of new or enlarging brain metastases, and are not using&#xD;
             steroids for at least 7 days prior to trial treatment. This exception does not include&#xD;
             carcinomatous meningitis, which is excluded regardless of clinical stability.&#xD;
&#xD;
          -  Has an active infection requiring systemic therapy.&#xD;
&#xD;
          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality&#xD;
             that might confound the results of the trial, interfere with the patient's&#xD;
             participation for the full duration of the trial, or is not in the best interest of&#xD;
             the patient to participate, in the opinion of the treating investigator. Has known&#xD;
             psychiatric or substance abuse disorders that would interfere with cooperation with&#xD;
             the requirements of the trial.&#xD;
&#xD;
          -  For female participants: Is pregnant or breastfeeding, or expecting to conceive within&#xD;
             the projected duration of the trial, starting with the pre-screening or screening&#xD;
             visit through one month after the last dose of trial treatment.&#xD;
&#xD;
          -  For male participants: Is expecting to impregnate a sexual partner within the&#xD;
             projected duration of the trial, starting with the pre-screening or screening visit&#xD;
             through one month after the last dose of trial treatment.&#xD;
&#xD;
          -  Patients with evidence of iron overload, defined as a transferrin saturation &gt; 45&#xD;
             percent AND serum ferritin &gt; 200 ng/mL (males) or &gt;150 ng/mL (females).&#xD;
&#xD;
          -  Current, serious, clinically significant cardiac arrhythmias as determined by the&#xD;
             investigator, or patient receiving a digitalis derivative.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Piedmont Cancer Institute</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30318</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Piedmont Cancer Institute</name>
      <address>
        <city>Fayetteville</city>
        <state>Georgia</state>
        <zip>30214</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Piedmont Cancer Institute</name>
      <address>
        <city>Newnan</city>
        <state>Georgia</state>
        <zip>30265</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>December 5, 2018</study_first_submitted>
  <study_first_submitted_qc>January 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 9, 2019</study_first_posted>
  <last_update_submitted>May 30, 2019</last_update_submitted>
  <last_update_submitted_qc>May 30, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 31, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Metastatic Pancreatic Cancer</keyword>
  <keyword>Cancer</keyword>
  <keyword>Pancreatic</keyword>
  <keyword>Vitamin C</keyword>
  <keyword>Ascorbic Acid</keyword>
  <keyword>Paclitaxel Protein Bound</keyword>
  <keyword>Cisplatin</keyword>
  <keyword>Gemcitabine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pancreatic Neoplasms</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>Paclitaxel</mesh_term>
    <mesh_term>Gemcitabine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03797443
org study id: PAN-VITC
nct id: NCT03797443
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to see if a combination of paclitaxel protein bound (also known
      as nab-paclitaxel), gemcitabine, and cisplatin when given with high dose Ascorbic Acid will
      be safe and effective in individuals with untreated metastatic pancreatic cancer.

      Vitamin C is a nutrient found in food and dietary supplements. It protects cells and also
      plays a key role in making collagen (which provides strength and structure to skin, bones,
      tissues and tendons). High-dose vitamin C may be given by intravenous (IV) infusion (through
      a vein into the bloodstream) or orally (taken by mouth). When taken by intravenous infusion,
      vitamin C can reach much higher levels in the blood than when the same amount is taken by
      mouth. Some human studies of high-dose IV vitamin C in patients with cancer have shown
      improved quality of life, as well as improvements in physical, mental, and emotional
      functions, symptoms of fatigue, nausea and vomiting, pain, and appetite loss. Intravenous
      high-dose ascorbic acid has caused very few side effects in clinical trials.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Ascorbic Acid Paclitaxel Protein Bound Cisplatin Gemcitabine
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose
time frame: approx 63 days
description: To determine the maximum tolerated dose (MTD) of high dose ascorbic acid (AA) with triple therapy of nanoparticle paclitaxel protein bound+ cisplatin + gemcitabine (NABPLAGEM) in patients with advanced stage IV metastatic pancreatic cancer
measure: Disease control rate (CR+PR+SD x18 weeks)
time frame: approx 63 days
description: To determine the preliminary efficacy (Disease control rate of CR+ PR+SD X 18 weeks) of the combination of high dose ascorbic acid (AA) at MTD with triple therapy of nanoparticle albumin- bound paclitaxel + cisplatin + gemcitabine (NABPLAGEM) in patients with advanced stage IV metastatic pancreatic cancer.
measure: Incidence of Treatment
time frame: 63 days
description: Lab testing will be completed to evaluate standard of care labs for subject safety
measure: Percent of patients who normalize their CA19-9
time frame: 63 days
description: Lab testing will be completed to evaluate normalization of CA19-19
measure: Overall survival (OS)
time frame: 12 weeks
description: Telephone followup will be conducted every 12 weeks from the last dose of treatment to determine survival status
measure: Progression free
time frame: approximately 12 weeks from last study treatment ]
description: Telephone followup will be conducted every 12 weeks from the last dose of treatment to determine status of disease progression
measure: Changes in patient's self-reported quality of life
time frame: 63 days
description: Changes in patient's self-reported quality of life will be determined by administering the MD Anderson Symptom Inventory for Gastrointestinal Cancer (MDASI-GI) to assess the severity of multiple gastrointestinal cancer-related syymptoms and the impact of these symptoms of daily functiong.
measure: Changes in patient's self-reported pain levels
time frame: 63 days
description: Changes in patient's self-reported pain levels will be determined by administering the Brief Pain Inventory (BPI) to assess the severity of pain and the impact of pain on daily functions.
arm group label: AA NABPLAGEM
arm group type: Experimental
description: Ascorbic Acid Paclitaxel protein-bound cisplatin gemcitabine
intervention type: Drug
intervention name: Ascorbic Acid
description: Four escalating dose levels are planned in order to determine the MTD for Phase II
The dose level for Phase II patients will be determined following completion of the Phase 1b study based on response from 3-6 patients receiving the designated dose level of ascorbic acid.
arm group label: AA NABPLAGEM
other name: Vitamin C
intervention type: Drug
intervention name: nab paclitaxel
description: 30 minute IV infusions on days 1 and 8 repeated every 21 days, followed by Cisplatin
arm group label: AA NABPLAGEM
intervention type: Drug
intervention name: Cisplatin
description: 60minute IV infusion on days 1 and 8 repeated every 21 days followed by Gemcitabine
arm group label: AA NABPLAGEM
intervention type: Drug
intervention name: Gemcitabine
description: 30 minute IV infusion on days 1 and 8 repeated every 21 days
arm group label: AA NABPLAGEM
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Pancreatic Neoplasms
mesh term: Ascorbic Acid
mesh term: Paclitaxel
mesh term: Gemcitabine
sharing ipd: No