<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/NCT04481672</url>
  </required_header>
  <id_info>
    <org_study_id>19-801</org_study_id>
    <nct_id>NCT04481672</nct_id>
  </id_info>
  <brief_title>Intravenous Magnesium in Patients Receiving Cisplatin</brief_title>
  <official_title>Pilot and Feasibility Study of Intravenous Magnesium in Patients Receiving Hyperthermic Intraoperative Chemotherapy With Cisplatin (HIOCC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dana-Farber Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Dana-Farber Cancer Institute</source>
  <oversight_info>
    <has_dmc>No</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>
      This research study, is trying to determine the highest dose of magnesium that can be given&#xD;
      safely to people with malignant mesothelioma receiving intraoperative chemotherapy with&#xD;
      cisplatin who are at risk for acute kidney injury.&#xD;
&#xD;
      The name(s) of the study drug involved in this study is&#xD;
&#xD;
        -  magnesium sulfate.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This research study is a phase 1 pilot study, which is the first time investigators are&#xD;
      examining larger doses of magnesium in patients receiving cisplatin and the effect of&#xD;
      intravenous magnesium administration on blood magnesium levels. In previous studies it was&#xD;
      found that patients with lower blood magnesium levels were at higher risk of acute kidney&#xD;
      injury. The study is looking to determine the best dose(s) of intravenous magnesium to&#xD;
      administer safely without severe or unmanageable side effects in participants. The purpose of&#xD;
      the study is also to determine the dose of intravenous magnesium needed to achieve a target&#xD;
      level.&#xD;
&#xD;
      The U.S. Food and Drug Administration (FDA) has not approved magnesium for people with&#xD;
      mesothelioma receiving cisplatin but it has been approved for other uses.&#xD;
&#xD;
      The research study procedures include: screening for eligibility and study treatment at&#xD;
      participant's preoperative visit with their thoracic surgeon. Intravenous magnesium will be&#xD;
      administered in the hospital, the night prior to surgery, and take place over 36 hours.&#xD;
      Participants will followed for 4 days on postoperative days 1, 2, and 3.&#xD;
&#xD;
      It is expected that about 10 people will take part in this research study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 30, 2021</start_date>
  <completion_date type="Actual">December 30, 2021</completion_date>
  <primary_completion_date type="Actual">December 30, 2021</primary_completion_date>
  <phase>Phase 1</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>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Feasibility and acceptability as measured by participant rates of enrollment</measure>
    <time_frame>6 months</time_frame>
    <description>Feasibility assessed by % of patients that agree to participate. Project feasible if &gt;30% of the patients approached agree to participate</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0</measure>
    <time_frame>Time of magnesium infusion till 2 days.</time_frame>
    <description>NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Magnesium Level</measure>
    <time_frame>Day of surgery through postoperative day 3.</time_frame>
    <description>Assess the amount of IV magnesium needed to reach a target level of 3 to 4.8mg/dl. Magnesium levels will be measured at multiple time points. We want &gt;80% (≥32/40) of the time-averaged, postoperative magnesium levels to be within the target range of 3 to 4.8 mg/dl.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tubular Injury Markers</measure>
    <time_frame>From admission through postoperative day 3</time_frame>
    <description>Changes in urinary KIM-1 and urinary NGAL levels in order to assess intra- and interassay variability</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Mesothelioma</condition>
  <arm_group>
    <arm_group_label>Magnesium Sulfate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Starting the night before surgery participants will receive intravenous infusion of magnesium over approximately 36 hours. Dosage amounts will vary among participants as the study is determining the highest dose of magnesium that can be administered safely without severe or unmanageable side effects. The first 5 participants of the study will all receive the same dose of magnesium. The decision to test other doses of magnesium in 5 additional participants will depend on magnesium levels and dose tolerance outcomes in the first 5 participants.&#xD;
Participants will be followed for 4 days and undergo blood test to measure magnesium levels at the time of hospital admittance, the morning prior to the surgery, twice immediately after surgery, and twice a day for 3 days after the surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Magnesium Sulfate</intervention_name>
    <description>Intravenous infusion of magnesium sulfate prior to intraoperative chemotherapy with cisplatin.</description>
    <arm_group_label>Magnesium Sulfate</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults ≥18 years with malignant mesothelioma admitted for HIOCC. Because no dosing or&#xD;
             adverse event data are currently available on the use of intravenous magnesium&#xD;
             participants &lt;18 years of age, children are excluded from this study, but will be&#xD;
             eligible for future pediatric studies.&#xD;
&#xD;
          -  Glomerular filtration rate (GFR)≥ 30 ml/min/1.73m2 at the time of enrollment&#xD;
&#xD;
          -  Patients must have the ability to understand and the willingness to sign a written&#xD;
             informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with a pre-treatment serum Magnesium level &gt;2.5 mg/dl or &lt;1.3 mg/dl at the&#xD;
             preoperative visit&#xD;
&#xD;
          -  Patients with AKI at the time of enrollment, assessed by Kidney Disease Improving&#xD;
             Outcomes Criteria (serum creatinine increase ≥1.5x baseline)&#xD;
&#xD;
          -  Patients with estimated glomerular filtration rate &lt;30 ml/min/1.73m2 at the time of&#xD;
             enrollment&#xD;
&#xD;
          -  Patients with neuromuscular disease (e.g., amyotrophic lateral sclerosis, multiple&#xD;
             sclerosis, muscular dystrophy, myasthenia gravis, myositis)&#xD;
&#xD;
          -  Patients with sustained bradycardia (heart rate &lt;50 beats per minute on 1 or more EKGs&#xD;
             in the preceding 90 days) or 2nd degree AV heart block type 2 or higher with the&#xD;
             absence of a functioning pacemaker&#xD;
&#xD;
          -  Participants who are receiving any other investigational agents.&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to intravenous magnesium&#xD;
&#xD;
          -  Participants with uncontrolled intercurrent illness.&#xD;
&#xD;
          -  Participants with psychiatric illness/social situations that would limit compliance&#xD;
             with study requirements.&#xD;
&#xD;
          -  Pregnant women are excluded from this study because they may need magnesium for&#xD;
             treatment of preeclampsia or eclampsia, apart from this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Shruti Gupta, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Brigham and Women's Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>David E. Leaf, MD, MMSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Brigham and Women's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>July 19, 2020</study_first_submitted>
  <study_first_submitted_qc>July 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 22, 2020</study_first_posted>
  <last_update_submitted>January 10, 2022</last_update_submitted>
  <last_update_submitted_qc>January 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 11, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dana-Farber Cancer Institute</investigator_affiliation>
    <investigator_full_name>Shruti Gupta</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Mesothelioma</keyword>
  <keyword>Magnesium Sulfate</keyword>
  <keyword>intraoperative cisplatin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mesothelioma</mesh_term>
    <mesh_term>Mesothelioma, Malignant</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Magnesium Sulfate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Data can be shared no earlier than 1 year following the date of publication</ipd_time_frame>
    <ipd_access_criteria>BWH - Contact the Partners Innovations team at http://www.partners.org/innovation DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu</ipd_access_criteria>
  </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/NCT04481672
org study id: 19-801
nct id: NCT04481672
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This research study, is trying to determine the highest dose of magnesium that can be given
      safely to people with malignant mesothelioma receiving intraoperative chemotherapy with
      cisplatin who are at risk for acute kidney injury.

      The name(s) of the study drug involved in this study is

        -  magnesium sulfate.
This research study is a phase 1 pilot study, which is the first time investigators are
      examining larger doses of magnesium in patients receiving cisplatin and the effect of
      intravenous magnesium administration on blood magnesium levels. In previous studies it was
      found that patients with lower blood magnesium levels were at higher risk of acute kidney
      injury. The study is looking to determine the best dose(s) of intravenous magnesium to
      administer safely without severe or unmanageable side effects in participants. The purpose of
      the study is also to determine the dose of intravenous magnesium needed to achieve a target
      level.

      The U.S. Food and Drug Administration (FDA) has not approved magnesium for people with
      mesothelioma receiving cisplatin but it has been approved for other uses.

      The research study procedures include: screening for eligibility and study treatment at
      participant's preoperative visit with their thoracic surgeon. Intravenous magnesium will be
      administered in the hospital, the night prior to surgery, and take place over 36 hours.
      Participants will followed for 4 days on postoperative days 1, 2, and 3.

      It is expected that about 10 people will take part in this research study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Feasibility and acceptability as measured by participant rates of enrollment
time frame: 6 months
description: Feasibility assessed by % of patients that agree to participate. Project feasible if >30% of the patients approached agree to participate
measure: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0
time frame: Time of magnesium infusion till 2 days.
description: NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
measure: Magnesium Level
time frame: Day of surgery through postoperative day 3.
description: Assess the amount of IV magnesium needed to reach a target level of 3 to 4.8mg/dl. Magnesium levels will be measured at multiple time points. We want >80% (≥32/40) of the time-averaged, postoperative magnesium levels to be within the target range of 3 to 4.8 mg/dl.
measure: Tubular Injury Markers
time frame: From admission through postoperative day 3
description: Changes in urinary KIM-1 and urinary NGAL levels in order to assess intra- and interassay variability
arm group label: Magnesium Sulfate
arm group type: Experimental
description: Starting the night before surgery participants will receive intravenous infusion of magnesium over approximately 36 hours. Dosage amounts will vary among participants as the study is determining the highest dose of magnesium that can be administered safely without severe or unmanageable side effects. The first 5 participants of the study will all receive the same dose of magnesium. The decision to test other doses of magnesium in 5 additional participants will depend on magnesium levels and dose tolerance outcomes in the first 5 participants.
Participants will be followed for 4 days and undergo blood test to measure magnesium levels at the time of hospital admittance, the morning prior to the surgery, twice immediately after surgery, and twice a day for 3 days after the surgery.
intervention type: Drug
intervention name: Magnesium Sulfate
description: Intravenous infusion of magnesium sulfate prior to intraoperative chemotherapy with cisplatin.
arm group label: Magnesium Sulfate
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Shruti Gupta, MD, MPH
role: Principal Investigator
affiliation: Brigham and Women's Hospital
last name: David E. Leaf, MD, MMSc
role: Principal Investigator
affiliation: Brigham and Women's Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Dana-Farber Cancer Institute
investigator full name: Shruti Gupta
investigator title: Principal Investigator
mesh term: Mesothelioma
mesh term: Mesothelioma, Malignant
mesh term: Magnesium Sulfate
sharing ipd: Yes
ipd description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Data can be shared no earlier than 1 year following the date of publication
ipd access criteria: BWH - Contact the Partners Innovations team at http://www.partners.org/innovation DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu