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/NCT06010277</url>
    </required_header>
    <id_info>
      <org_study_id>1891</org_study_id>
      <nct_id>NCT06010277</nct_id>
    </id_info>
    <brief_title>Folinic Acid for Prevention of Pemetrexed-induced Toxicity</brief_title>
    <acronym>FLEX</acronym>
    <official_title>The Effect of Oral Folinic Acid Rescue Therapy on Pemetrexed Induced Neutropenia: A Randomized Open-label Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Amphia Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Albert Schweitzer Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Amphia Hospital</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>
    </oversight_info>
    <brief_summary>
      <textblock>
        Objective The main objective is to evaluate the haematological toxicity in patients who use&#xD;
        pemetrexed with and without rescue therapy with folinic acid.&#xD;
  &#xD;
        Primary endpoint Difference between treatment groups in neutrophil count (*109/L) at day 8-10&#xD;
        after administration of pemetrexed (nadir).&#xD;
  &#xD;
        Secondary endpoints The grade neutropenia (according to the CTCAE version 5, 2017) at day&#xD;
        8-10, the homocysteine plasma levels at baseline (predictor for developing toxicity), the&#xD;
        efficacy of chemotherapy treatment based on response CT after cycle 2 and 4 and the incidence&#xD;
        of discontinuation, dose delays and dose reductions of pemetrexed.&#xD;
  &#xD;
        Trial design The FLEX-trial is a multi-centre, open label, double arm, randomized trial to&#xD;
        compare neutropenia in patients with and without folinic acid rescue therapy where subjects&#xD;
        are participating for 4 treatment cycles.&#xD;
  &#xD;
        Population In total 50 patients (25 in each arm), &gt;18 years with stage IV non-small cell lung&#xD;
        cancer (NSCLC) or mesothelioma treated with pemetrexed (in combination with other chemo- or&#xD;
        immunotherapy) are eligible for inclusion.&#xD;
  &#xD;
        Interventions Follow-up will take place during the first 4 cycles of chemotherapy with&#xD;
        pemetrexed. Patients in the intervention-arm will receive oral folinic acid orally 4 times&#xD;
        45mg / day for 3 days, starting 24 hours after the administration of pemetrexed.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">February 6, 2023</start_date>
    <completion_date type="Anticipated">January 2024</completion_date>
    <primary_completion_date type="Anticipated">January 2024</primary_completion_date>
    <phase>Phase 4</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>Prevention</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Difference in neutrophil count (*109/L) at day 8-10 after pemetrexed administration during 2 cycles of chemotherapy</measure>
      <time_frame>Between day 8-10 in the first 2 cycles (each cycle is 21 days)</time_frame>
      <description>To evaluate the haematological toxicity (continuous measure) in patients who use pemetrexed with and without rescue therapy with folinic acid.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Grade neutropenia (according to the CTCAE version 5, 2017) at day 8-10 after pemetrexed administration during 2 cycles of chemotherapy</measure>
      <time_frame>Between day 8-10 in the first 2 cycles (each cycle is 21 days)</time_frame>
      <description>To evaluate the difference in haematological toxicity based on the CTCAE criteria for neutrophil count</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Homocysteine plasma levels at baseline (μmol/L)</measure>
      <time_frame>Once, before the start of the first cycle (each cycle is 21 days)</time_frame>
      <description>To evaluate the influence of baseline homocysteine plasma levels on occurrence of haematological toxicity.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy based on response CT after cycle 2 and 4 (categorical: response, partial response, progression)</measure>
      <time_frame>After the second and fourth cycle (each cycle is 21 days)</time_frame>
      <description>To evaluate the efficacy of the treatment with pemetrexed (based on CT-scan).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of discontinuation, dose delays and dose reductions of pemetrexed</measure>
      <time_frame>3 months</time_frame>
      <description>To evaluate the incidence of treatment delay or dose reduction of pemetrexed.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">50</enrollment>
    <condition>NSCLC</condition>
    <condition>Mesothelioma</condition>
    <condition>Thymoma</condition>
    <arm_group>
      <arm_group_label>Folinic acid arm</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients in the intervention-arm will receive oral folinic acid orally 4 times 45mg / day for 3 days, starting 24 hours after the administration of pemetrexed.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>No folinic acid arm</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>Patients will be treated according to regular care.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Folinic acid</intervention_name>
      <description>Follow-up will take place during the first 4 cycles of chemotherapy with pemetrexed. Patients in the intervention-arm will receive oral folinic acid orally 4 times 45mg / day for 3 days, starting 24 hours after the administration of pemetrexed.</description>
      <arm_group_label>Folinic acid arm</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          In order to be eligible to participate in this study, a subject must meet all of the&#xD;
          following criteria:&#xD;
  &#xD;
            1. ≥18 years old&#xD;
  &#xD;
            2. Eligible for treatment with pemetrexed-based chemotherapy based on indication.&#xD;
  &#xD;
            3. ECOG performance score of 0-2.&#xD;
  &#xD;
            4. Subject is able and willing to sign the Informed Consent Form&#xD;
  &#xD;
          A potential subject who meets any of the following criteria will be excluded from&#xD;
          participation in this study:&#xD;
  &#xD;
            1. Contraindications for treatment with folinic acid in line with the SmPC.&#xD;
  &#xD;
                 1. Hypersensitivity to the active substance or to any of the excipients.&#xD;
  &#xD;
                 2. Anaemia caused by vitamin B12 deficiency.&#xD;
  &#xD;
            2. The presence of clinically relevant drug-drug interactions, according to the current&#xD;
               SmPC of folinic acid.&#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_contact>
      <last_name>Ramon Contrucci, MSc</last_name>
      <phone>0765954354</phone>
      <email>rcontrucci@amphia.nl</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Nikki de Rouw, Phd</last_name>
      <phone>0765957757</phone>
      <email>nderouw@amphia.nl</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Amphia Hospital</name>
        <address>
          <city>Breda</city>
          <state>Noord Brabant</state>
          <zip>4817</zip>
          <country>Netherlands</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Ramon Contrucci, MSc</last_name>
        <phone>+31765954354</phone>
        <email>Rcontrucci@amphia.nl</email>
      </contact>
      <contact_backup>
        <last_name>Nikki de Rouw, Phd</last_name>
        <phone>+31765957757</phone>
        <email>NdeRouw@amphia.nl</email>
      </contact_backup>
    </location>
    <location>
      <facility>
        <name>Albert Schweitzer Hospital</name>
        <address>
          <city>Dordrecht</city>
          <state>Zuid Holland</state>
          <zip>3318</zip>
          <country>Netherlands</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Ramon Contrucci, MSc</last_name>
        <phone>+31765954354</phone>
        <email>RContrucci@amphia.nl</email>
      </contact>
      <contact_backup>
        <last_name>Charlotte van Kesteren, Phd</last_name>
        <email>cvankesteren@asz.nl</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>Netherlands</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>January 26, 2023</study_first_submitted>
    <study_first_submitted_qc>August 17, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 24, 2023</study_first_posted>
    <last_update_submitted>August 17, 2023</last_update_submitted>
    <last_update_submitted_qc>August 17, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 24, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Amphia Hospital</investigator_affiliation>
      <investigator_full_name>Dr. N. (Nikki) de Rouw</investigator_full_name>
      <investigator_title>Dr. Nikki de Rouw, principal investigator</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Mesothelioma</mesh_term>
      <mesh_term>Thymoma</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Leucovorin</mesh_term>
      <mesh_term>Folic Acid</mesh_term>
      <mesh_term>Levoleucovorin</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <provided_document_section>
      <provided_document>
        <document_type>Study Protocol and Statistical Analysis Plan</document_type>
        <document_has_protocol>Yes</document_has_protocol>
        <document_has_icf>No</document_has_icf>
        <document_has_sap>Yes</document_has_sap>
        <document_date>January 11, 2023</document_date>
        <document_url>https://ClinicalTrials.gov/ProvidedDocs/77/NCT06010277/Prot_SAP_000.pdf</document_url>
      </provided_document>
    </provided_document_section>
    <!-- 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/NCT06010277
  org study id: 1891
  nct id: NCT06010277
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Objective The main objective is to evaluate the haematological toxicity in patients who use
        pemetrexed with and without rescue therapy with folinic acid.
  
        Primary endpoint Difference between treatment groups in neutrophil count (*109/L) at day 8-10
        after administration of pemetrexed (nadir).
  
        Secondary endpoints The grade neutropenia (according to the CTCAE version 5, 2017) at day
        8-10, the homocysteine plasma levels at baseline (predictor for developing toxicity), the
        efficacy of chemotherapy treatment based on response CT after cycle 2 and 4 and the incidence
        of discontinuation, dose delays and dose reductions of pemetrexed.
  
        Trial design The FLEX-trial is a multi-centre, open label, double arm, randomized trial to
        compare neutropenia in patients with and without folinic acid rescue therapy where subjects
        are participating for 4 treatment cycles.
  
        Population In total 50 patients (25 in each arm), >18 years with stage IV non-small cell lung
        cancer (NSCLC) or mesothelioma treated with pemetrexed (in combination with other chemo- or
        immunotherapy) are eligible for inclusion.
  
        Interventions Follow-up will take place during the first 4 cycles of chemotherapy with
        pemetrexed. Patients in the intervention-arm will receive oral folinic acid orally 4 times
        45mg / day for 3 days, starting 24 hours after the administration of pemetrexed.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Prevention
  masking: None (Open Label)
  measure: Difference in neutrophil count (*109/L) at day 8-10 after pemetrexed administration during 2 cycles of chemotherapy
  time frame: Between day 8-10 in the first 2 cycles (each cycle is 21 days)
  description: To evaluate the haematological toxicity (continuous measure) in patients who use pemetrexed with and without rescue therapy with folinic acid.
  measure: Grade neutropenia (according to the CTCAE version 5, 2017) at day 8-10 after pemetrexed administration during 2 cycles of chemotherapy
  time frame: Between day 8-10 in the first 2 cycles (each cycle is 21 days)
  description: To evaluate the difference in haematological toxicity based on the CTCAE criteria for neutrophil count
  measure: Homocysteine plasma levels at baseline (μmol/L)
  time frame: Once, before the start of the first cycle (each cycle is 21 days)
  description: To evaluate the influence of baseline homocysteine plasma levels on occurrence of haematological toxicity.
  measure: Efficacy based on response CT after cycle 2 and 4 (categorical: response, partial response, progression)
  time frame: After the second and fourth cycle (each cycle is 21 days)
  description: To evaluate the efficacy of the treatment with pemetrexed (based on CT-scan).
  measure: Incidence of discontinuation, dose delays and dose reductions of pemetrexed
  time frame: 3 months
  description: To evaluate the incidence of treatment delay or dose reduction of pemetrexed.
  arm group label: Folinic acid arm
  arm group type: Experimental
  description: Patients in the intervention-arm will receive oral folinic acid orally 4 times 45mg / day for 3 days, starting 24 hours after the administration of pemetrexed.
  arm group label: No folinic acid arm
  arm group type: No Intervention
  description: Patients will be treated according to regular care.
  intervention type: Drug
  intervention name: Folinic acid
  description: Follow-up will take place during the first 4 cycles of chemotherapy with pemetrexed. Patients in the intervention-arm will receive oral folinic acid orally 4 times 45mg / day for 3 days, starting 24 hours after the administration of pemetrexed.
  arm group label: Folinic acid arm
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Ramon Contrucci, MSc
  phone: 0765954354
  email: rcontrucci@amphia.nl
  last name: Nikki de Rouw, Phd
  phone: 0765957757
  email: nderouw@amphia.nl
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  facility: 
  status: Not yet recruiting
  contact: 
  contact backup: 
  country: Netherlands
  responsible party type: Principal Investigator
  investigator affiliation: Amphia Hospital
  investigator full name: Dr. N. (Nikki) de Rouw
  investigator title: Dr. Nikki de Rouw, principal investigator
  mesh term: Mesothelioma
  mesh term: Thymoma
  mesh term: Leucovorin
  mesh term: Folic Acid
  mesh term: Levoleucovorin
  sharing ipd: Undecided
  provided document: 