<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/NCT04488783</url>
  </required_header>
  <id_info>
    <org_study_id>4266-17-SMC</org_study_id>
    <nct_id>NCT04488783</nct_id>
  </id_info>
  <brief_title>Potentiation of Chemotherapy in Brain Tumors by Zinc</brief_title>
  <official_title>Potentiation of Chemotherapy in Brain Tumors by Zinc</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sheba Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sheba Medical Center</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Glioblastoma (GB) is the most common and aggressive type of primary malignant brain tumor in&#xD;
      adults. Despite advances in surgical resection, radiotherapy and chemotherapy, prognosis&#xD;
      remains very poor. Temozolomide (TMZ) as an alkylating agent has become part of GBM&#xD;
      management but it has contributed only marginally to prolongation of life in GBM patients.&#xD;
      Our aim is to evaluate the therapeutic potential of the trace element zinc to facilitate&#xD;
      temozolomide tumor cell toxicity in GBM. P53 gene is inactive/mutant in most of these&#xD;
      patients which may affect the resistance to apoptosis of tumor cells by chemotherapy. Zinc&#xD;
      (Zn) has a crucial role in the biology of p53, in that p53 binds to DNA through a&#xD;
      structurally complex domain stabilized by zinc atom. We have shown that the cytotoxic&#xD;
      activity of TMZ is substantially increased with the addition of zinc in vitro with GBM cell&#xD;
      lines as well as in vivo, with intracranial GBM xenografts. Numerous studies of zinc in&#xD;
      animal models and in human subjects support its use in the treatment and possibly the&#xD;
      prevention of cancer. Zinc has been consumed by the public as an essential mineral (and thus&#xD;
      is category A drug) in concentrations which allows this effect with Temozolomide. Vitamin C&#xD;
      could add to this by priming the immune system for lymphocyte- linked cancer killing. The&#xD;
      vitamin c increases the number of tumor infiltrating lymphocytes and enhances the activation&#xD;
      of the immune system.We propose a single arm phase II clinical trial in 30 newly diagnosed&#xD;
      GBM patients who will be treated with the standard chemo-radiotherapy with the addition of&#xD;
      zinc and vitamin C.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      We propose a single arm phase II clinical trial in 30 newly diagnosed GBM patients who will&#xD;
      be treated with the standard chemo-radiotherapy with the addition of daily zinc. We will&#xD;
      follow the toxicity, Progression free survival and overall survival of this group of&#xD;
      patients. We hope to demonstrate the anti-tumor activity of zinc that will enhance the&#xD;
      activity of temozolomide chemotherapy in adult glioblastoma patients. We will also follow the&#xD;
      safety and monitor quality of life during treatment. In this study, we will compare results&#xD;
      of patients receiving zinc to historical patient data. We will review patient portfolios with&#xD;
      GB tumors that received treatment as the subjects in this study in the last five years before&#xD;
      the study began. Collecting the data and separating the identified data from the file in a&#xD;
      way that cannot be retrieved in any way will be done by a staff member from Dr Ruty Shai's&#xD;
      laboratory who is authorized to open medical files. We will adjust the age and number of&#xD;
      patients in each gender. Data collected: date of birth, age of disease development, gender,&#xD;
      data after receiving treatment: Progression free survival and overall survival of this group&#xD;
      of patients, side effects, and quality of life.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Anticipated">July 30, 2020</start_date>
  <completion_date type="Anticipated">December 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">July 30, 2022</primary_completion_date>
  <phase>N/A</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>progression free survival (PFS)</measure>
    <time_frame>year 1</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>overall survival (OS)</measure>
    <time_frame>year 2</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tcell count</measure>
    <time_frame>year 2</time_frame>
    <description>Blood test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of Interleukin 6</measure>
    <time_frame>year 2</time_frame>
    <description>Interleukin 6 and Tumor Necrosis Factor quantification</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor Necrosis Factor quantification</measure>
    <time_frame>year 2</time_frame>
    <description>Blood test</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Newly Diagnosed Glioblastoma Who Underwent at Least Partial Resection of the Tumor Surgically</condition>
  <arm_group>
    <arm_group_label>Glioblastoma patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>newly diagnosed GB who underwent at least partial resection of the tumor surgically</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>zinc and ascorbate</intervention_name>
    <description>oral zinc and ascorbate</description>
    <arm_group_label>Glioblastoma patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males and Females,&#xD;
&#xD;
          -  age ≥ 18 years old,&#xD;
&#xD;
          -  newly diagnosed GBM, Karnofsky performance status of ≥ 70,&#xD;
&#xD;
          -  after partial resection or gross tumor resection (GTR) who recovered from surgical&#xD;
             resection.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  GB patients with less than 20% of tumor removed,&#xD;
&#xD;
          -  Prior treatment for GB (other than surgical resection),&#xD;
&#xD;
          -  any known malignancy outside of the brain in the last 5 years,&#xD;
&#xD;
          -  in ability to swallow drugs.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Ruty Shai, PhD</last_name>
    <phone>972-543938318</phone>
    <email>ruty.shai@sheba.health.gov.il</email>
  </overall_contact>
  <location>
    <facility>
      <name>Sheba Medical Center</name>
      <address>
        <city>Ramat Gan</city>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ruty Shai, Ph.D</last_name>
      <phone>972543938318</phone>
      <email>ruty.shai@sheba.health.gov.il</email>
    </contact>
    <investigator>
      <last_name>Ruty Shai, Ph.D</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2020</study_first_posted>
  <last_update_submitted>July 27, 2020</last_update_submitted>
  <last_update_submitted_qc>July 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 28, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sheba Medical Center</investigator_affiliation>
    <investigator_full_name>Dr. Leor Zach, MD</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>GBM</keyword>
  <keyword>glioblastoma</keyword>
  <keyword>zinc</keyword>
  <keyword>vitamin C</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioblastoma</mesh_term>
  </condition_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/NCT04488783
org study id: 4266-17-SMC
nct id: NCT04488783
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Glioblastoma (GB) is the most common and aggressive type of primary malignant brain tumor in
      adults. Despite advances in surgical resection, radiotherapy and chemotherapy, prognosis
      remains very poor. Temozolomide (TMZ) as an alkylating agent has become part of GBM
      management but it has contributed only marginally to prolongation of life in GBM patients.
      Our aim is to evaluate the therapeutic potential of the trace element zinc to facilitate
      temozolomide tumor cell toxicity in GBM. P53 gene is inactive/mutant in most of these
      patients which may affect the resistance to apoptosis of tumor cells by chemotherapy. Zinc
      (Zn) has a crucial role in the biology of p53, in that p53 binds to DNA through a
      structurally complex domain stabilized by zinc atom. We have shown that the cytotoxic
      activity of TMZ is substantially increased with the addition of zinc in vitro with GBM cell
      lines as well as in vivo, with intracranial GBM xenografts. Numerous studies of zinc in
      animal models and in human subjects support its use in the treatment and possibly the
      prevention of cancer. Zinc has been consumed by the public as an essential mineral (and thus
      is category A drug) in concentrations which allows this effect with Temozolomide. Vitamin C
      could add to this by priming the immune system for lymphocyte- linked cancer killing. The
      vitamin c increases the number of tumor infiltrating lymphocytes and enhances the activation
      of the immune system.We propose a single arm phase II clinical trial in 30 newly diagnosed
      GBM patients who will be treated with the standard chemo-radiotherapy with the addition of
      zinc and vitamin C.
We propose a single arm phase II clinical trial in 30 newly diagnosed GBM patients who will
      be treated with the standard chemo-radiotherapy with the addition of daily zinc. We will
      follow the toxicity, Progression free survival and overall survival of this group of
      patients. We hope to demonstrate the anti-tumor activity of zinc that will enhance the
      activity of temozolomide chemotherapy in adult glioblastoma patients. We will also follow the
      safety and monitor quality of life during treatment. In this study, we will compare results
      of patients receiving zinc to historical patient data. We will review patient portfolios with
      GB tumors that received treatment as the subjects in this study in the last five years before
      the study began. Collecting the data and separating the identified data from the file in a
      way that cannot be retrieved in any way will be done by a staff member from Dr Ruty Shai's
      laboratory who is authorized to open medical files. We will adjust the age and number of
      patients in each gender. Data collected: date of birth, age of disease development, gender,
      data after receiving treatment: Progression free survival and overall survival of this group
      of patients, side effects, and quality of life.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: progression free survival (PFS)
time frame: year 1
measure: overall survival (OS)
time frame: year 2
measure: Tcell count
time frame: year 2
description: Blood test
measure: Level of Interleukin 6
time frame: year 2
description: Interleukin 6 and Tumor Necrosis Factor quantification
measure: Tumor Necrosis Factor quantification
time frame: year 2
description: Blood test
arm group label: Glioblastoma patients
arm group type: Experimental
description: newly diagnosed GB who underwent at least partial resection of the tumor surgically
intervention type: Dietary Supplement
intervention name: zinc and ascorbate
description: oral zinc and ascorbate
arm group label: Glioblastoma patients
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: Ruty Shai, PhD
phone: 972-543938318
email: ruty.shai@sheba.health.gov.il
facility: 
status: Recruiting
contact: 
investigator: 
country: Israel
responsible party type: Principal Investigator
investigator affiliation: Sheba Medical Center
investigator full name: Dr. Leor Zach, MD
investigator title: MD
mesh term: Glioblastoma
sharing ipd: No