xml: <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/NCT05977738</url>
    </required_header>
    <id_info>
      <org_study_id>2023-505743-38-00</org_study_id>
      <secondary_id>UTN U1111-1294-4392</secondary_id>
      <nct_id>NCT05977738</nct_id>
    </id_info>
    <brief_title>Repurposed Drugs in Research for Cancer Clinical Trials- Pitavastatin</brief_title>
    <acronym>ReDiReCCT-Pita</acronym>
    <official_title>Phase 0 lead-in Trial of Pitavastatin in Primary and Recurrent Glioblastoma Patients</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>C.Dirven</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Erasmus Medical Center</source>
    <oversight_info>
      <has_dmc>No</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>
        The goal of this Phase 0 trial is to study if pre-operative oral pitavastatin administration&#xD;
        reaches the tumour in patients with primary or a recurrent glioblastoma. The main question[s]&#xD;
        it aims to answer are:&#xD;
  &#xD;
          -  Does pitavastatin reach a cytotoxic concentration in gadolinium-enhanced tumour tissue&#xD;
             after oral administration?&#xD;
  &#xD;
          -  Does pitavastatin achieve a concentration that can synergize with temozolomide in the&#xD;
             gadolinium non-enhanced area of the tumour?&#xD;
  &#xD;
        Participants will receive pitavastatin in differing dosages a week before their elective&#xD;
        surgery and blood and tumour samples will be collected.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 2023</start_date>
    <completion_date type="Anticipated">July 2024</completion_date>
    <primary_completion_date type="Anticipated">May 2024</primary_completion_date>
    <phase>Early Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <intervention_model_description>open label, dose-finding, 3+3-like dose-escalation study design</intervention_model_description>
      <primary_purpose>Other</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Intratumoral pitavastatin concentration as assessed by LC-MS analysis on tumour tissue.</measure>
      <time_frame>From the last patient visit of each dose cohort at day 9 to 2 weeks after the last patient visit of each dose cohort.</time_frame>
      <description>Detection of pitavastatin in gadolinium enhanced and gadolinium non-enhanced tumour. tissue in relation to serum levels after preoperative administration.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Tolerability of short-term pitavastatin treatment as assesseb by a customized questionnaire related to adverse events found during the use of pitavastatin.</measure>
      <time_frame>From the last patient visit of the last dose cohort to 2 weeks after the last patient visit of the last dose cohort on day 9.</time_frame>
      <description>Number of AEs, SAEs and SUSARs collected at the end of the trial. Events will be scored according to CTC criteria version 5.0 (Published November 27th, 2017).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Relation of plasma pitavastatin concentration and intratumoral pitavastatin concentration as assessed by LC-MS analysis on plasma and tumour tissue.</measure>
      <time_frame>From the moment the LC-MS analysis of the last patient tumour tissue and plasma is performed to two weeks after the last patient visit on day 9 of the last dose cohort.</time_frame>
      <description>Correlation of pitavastatin concentration in plasma to pitavastatin concentration in different tumour sites(gadolinium enhanced, gadolinium non-enhanced and tumour periphery).</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Differences in RNA expression after pitavastatin exposure in tumour tissue using RNA sequencing.</measure>
      <time_frame>From the last tumour tissue acquisition of the last patient of the last dose cohort to 3 months after all tissue is collected.</time_frame>
      <description>Using RNA sequencing on collected tumour samples from the gadolinium enhanced part of the tumour.</description>
    </other_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">18</enrollment>
    <condition>Glioblastoma Multiforme, Adult</condition>
    <condition>Recurrent Glioblastoma</condition>
    <arm_group>
      <arm_group_label>Dose group 1: 16 mg</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Pitavastatin 16 mg via oral route in the form of daily tablets for 6 days before SOC surgery</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dose group 2: 32 mg</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Pitavastatin 32 mg via oral route in the form of daily tablets for 6 days before SOC surgery</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Dose group 3: 48 mg</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Pitavastatin 48 mg via oral route in the form of daily tablets for 6 days before SOC surgery</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Pitavastatin calcium</intervention_name>
      <description>Daily Pitavastatin administration</description>
      <arm_group_label>Dose group 1: 16 mg</arm_group_label>
      <arm_group_label>Dose group 2: 32 mg</arm_group_label>
      <arm_group_label>Dose group 3: 48 mg</arm_group_label>
      <other_name>Alipza</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Eligible for resection of a suspected primary glioblastoma or a recurrent&#xD;
               glioblastoma.&#xD;
  &#xD;
            2. MRI- measurable disease preoperatively, defined as at least 1 contrast-enhancing&#xD;
               lesion, with 1 perpendicular measurement of at least 0.5 cm.&#xD;
  &#xD;
            3. Adequate Renal Function defined as: estimated glomerular filtration rate (eGFR) ≥ 60&#xD;
               mL/min/1.73 m2 by Chronic Disease Epidemiology Collaboration (CKD-EPI) equation.&#xD;
  &#xD;
            4. CK elevation 3 X ULN.&#xD;
  &#xD;
            5. Ability to understand and the willingness to sign a written informed consent document.&#xD;
  &#xD;
            6. Participant has voluntarily agreed to participate by giving written informed consent&#xD;
               Written informed consent for participation in the protocol must be obtained prior to&#xD;
               any screening procedures taking place.&#xD;
  &#xD;
            7. Willingness and ability to comply with all scheduled visits, treatment plans,&#xD;
               laboratory tests and other procedures.&#xD;
  &#xD;
            8. Age ≥18 years at time of consent.&#xD;
  &#xD;
            9. Ability and willingness to swallow oral medication.&#xD;
  &#xD;
           10. Confirmed negative serum pregnancy test (β-hCG) before starting study treatment or&#xD;
               participant who is no longer of childbearing potential due to surgical, chemical, or&#xD;
               natural menopause.&#xD;
  &#xD;
           11. For females of reproductive potential: use of highly effective contraception method&#xD;
               defined as one that results in a low failure rate (ie, less than 1% per year) when&#xD;
               used consistently and correctly.&#xD;
  &#xD;
           12. Females of child-bearing potential must agree not to breastfeed starting at screening,&#xD;
               and throughout the study period.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Pregnancy or lactation.&#xD;
  &#xD;
            2. Known allergic reactions to components of the pitavastatin calcium tablets.&#xD;
  &#xD;
            3. Patients with ALAT and ASAT levels 3 X ULN.&#xD;
  &#xD;
            4. Unwillingness to temporarily stop an already prescribed statin, during treatment with&#xD;
               pitavastatin.&#xD;
  &#xD;
            5. Active infection or fever &gt;38.5°C requiring systemic antibiotic, antifungal or&#xD;
               antiviral therapy.&#xD;
  &#xD;
            6. Concomitant use of cyclosporin, gemfibrozil, systemic fusidic acid, fibrates, niacin&#xD;
               or colchicine.&#xD;
  &#xD;
            7. Known to have active (acute or chronic) or uncontrolled severe infection, liver&#xD;
               disease such as cirrhosis, decompensated liver disease, unexplained elevated liver&#xD;
               transaminase levels, and active and chronic hepatitis as determined by the&#xD;
               investigator.&#xD;
  &#xD;
            8. Suspicion of oral malabsorption, influencing the uptake of drugs from the ileum, such&#xD;
               as Morbus Crohn.&#xD;
  &#xD;
            9. Treatment with another investigational drug or other intervention within 30 days prior&#xD;
               to enrolment or within 5 half-lives of the investigational product, whichever is&#xD;
               longer.&#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>Clemens Dirven, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Erasmus Medical Center</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Puspha Achaiber Sing, MD, MSc</last_name>
      <phone>+31107035993</phone>
      <email>p.achaibersing@erasmusmc.nl</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Judith Verhagen, PhD</last_name>
      <phone>+31650032401</phone>
      <email>j.verhagen-oldenampsen@erasmusmc.nl</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Erasmus MC</name>
        <address>
          <city>Rotterdam</city>
          <zip>3015 GE</zip>
          <country>Netherlands</country>
        </address>
      </facility>
      <contact>
        <last_name>Puspha Achaiber Sing, MSc</last_name>
        <phone>+31107035993</phone>
        <email>p.achaibersing@erasmusmc.nl</email>
      </contact>
      <contact_backup>
        <last_name>Judith Verhagen, PhD</last_name>
        <phone>+31650032401</phone>
        <email>j.verhagen-oldenampsen@erasmusmc.nl</email>
      </contact_backup>
      <investigator>
        <last_name>Clemens Dirven, MD, PhD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Netherlands</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 25, 2023</study_first_submitted>
    <study_first_submitted_qc>August 3, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 4, 2023</study_first_posted>
    <last_update_submitted>August 3, 2023</last_update_submitted>
    <last_update_submitted_qc>August 3, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 4, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Erasmus Medical Center</investigator_affiliation>
      <investigator_full_name>C.Dirven</investigator_full_name>
      <investigator_title>Prof. dr.</investigator_title>
    </responsible_party>
    <keyword>Phase 0</keyword>
    <keyword>GBM</keyword>
    <keyword>Glioma</keyword>
    <keyword>Pitavastatin</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Glioblastoma</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Pitavastatin</mesh_term>
      <mesh_term>Calcium</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05977738
  org study id: 2023-505743-38-00
  secondary id: UTN U1111-1294-4392
  nct id: NCT05977738
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  The goal of this Phase 0 trial is to study if pre-operative oral pitavastatin administration
        reaches the tumour in patients with primary or a recurrent glioblastoma. The main question[s]
        it aims to answer are:
  
          -  Does pitavastatin reach a cytotoxic concentration in gadolinium-enhanced tumour tissue
             after oral administration?
  
          -  Does pitavastatin achieve a concentration that can synergize with temozolomide in the
             gadolinium non-enhanced area of the tumour?
  
        Participants will receive pitavastatin in differing dosages a week before their elective
        surgery and blood and tumour samples will be collected.
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  intervention model description: open label, dose-finding, 3+3-like dose-escalation study design
  primary purpose: Other
  masking: None (Open Label)
  measure: Intratumoral pitavastatin concentration as assessed by LC-MS analysis on tumour tissue.
  time frame: From the last patient visit of each dose cohort at day 9 to 2 weeks after the last patient visit of each dose cohort.
  description: Detection of pitavastatin in gadolinium enhanced and gadolinium non-enhanced tumour. tissue in relation to serum levels after preoperative administration.
  measure: Tolerability of short-term pitavastatin treatment as assesseb by a customized questionnaire related to adverse events found during the use of pitavastatin.
  time frame: From the last patient visit of the last dose cohort to 2 weeks after the last patient visit of the last dose cohort on day 9.
  description: Number of AEs, SAEs and SUSARs collected at the end of the trial. Events will be scored according to CTC criteria version 5.0 (Published November 27th, 2017).
  measure: Relation of plasma pitavastatin concentration and intratumoral pitavastatin concentration as assessed by LC-MS analysis on plasma and tumour tissue.
  time frame: From the moment the LC-MS analysis of the last patient tumour tissue and plasma is performed to two weeks after the last patient visit on day 9 of the last dose cohort.
  description: Correlation of pitavastatin concentration in plasma to pitavastatin concentration in different tumour sites(gadolinium enhanced, gadolinium non-enhanced and tumour periphery).
  measure: Differences in RNA expression after pitavastatin exposure in tumour tissue using RNA sequencing.
  time frame: From the last tumour tissue acquisition of the last patient of the last dose cohort to 3 months after all tissue is collected.
  description: Using RNA sequencing on collected tumour samples from the gadolinium enhanced part of the tumour.
  arm group label: Dose group 1: 16 mg
  arm group type: Experimental
  description: Pitavastatin 16 mg via oral route in the form of daily tablets for 6 days before SOC surgery
  arm group label: Dose group 2: 32 mg
  arm group type: Experimental
  description: Pitavastatin 32 mg via oral route in the form of daily tablets for 6 days before SOC surgery
  arm group label: Dose group 3: 48 mg
  arm group type: Experimental
  description: Pitavastatin 48 mg via oral route in the form of daily tablets for 6 days before SOC surgery
  intervention type: Drug
  intervention name: Pitavastatin calcium
  description: Daily Pitavastatin administration
  arm group label: Dose group 1: 16 mg
  arm group label: Dose group 2: 32 mg
  arm group label: Dose group 3: 48 mg
  other name: Alipza
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Clemens Dirven, MD, PhD
  role: Principal Investigator
  affiliation: Erasmus Medical Center
  last name: Puspha Achaiber Sing, MD, MSc
  phone: +31107035993
  email: p.achaibersing@erasmusmc.nl
  last name: Judith Verhagen, PhD
  phone: +31650032401
  email: j.verhagen-oldenampsen@erasmusmc.nl
  facility: 
  contact: 
  contact backup: 
  investigator: 
  country: Netherlands
  responsible party type: Sponsor-Investigator
  investigator affiliation: Erasmus Medical Center
  investigator full name: C.Dirven
  investigator title: Prof. dr.
  mesh term: Glioblastoma
  mesh term: Pitavastatin
  mesh term: Calcium
  sharing ipd: Undecided