<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/NCT03265574</url>
  </required_header>
  <id_info>
    <org_study_id>2016152</org_study_id>
    <nct_id>NCT03265574</nct_id>
  </id_info>
  <brief_title>PROACT: Can we Prevent Chemotherapy-related Heart Damage in Patients With Breast Cancer and Lymphoma?</brief_title>
  <acronym>PROACT</acronym>
  <official_title>Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma: a Phase 3 Randomised, Open Label, Blinded Endpoint, Superiority Trial of Enalapril to Prevent Anthracycline-induced CardioToxicity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>South Tees Hospitals NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Newcastle University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Durham</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Newcastle-upon-Tyne Hospitals NHS Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>South Tees Hospitals NHS Foundation Trust</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>
      PROACT will establish the effectiveness of the angiotensin-converting enzyme inhibitor (ACEI)&#xD;
      enalapril maleate (enalapril) in preventing cardiotoxicity in patients with breast cancer and&#xD;
      non-Hodgkin lymphoma undergoing adjuvant epirubicin-based chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PROACT is a phase 3 randomised, open label, blinded endpoint, superiority trial of enalapril&#xD;
      to prevent anthracycline-induced in patients treated for breast cancer and lymphoma.&#xD;
&#xD;
      Anthracyclines used in the treatment of breast cancer cause damage to heart muscle cells;&#xD;
      this results in cell death (cardiotoxicity). In UK contemporary practice, epirubicin is the&#xD;
      most frequently used anthracycline.&#xD;
&#xD;
      Patients due to receive adjuvant anthracycline chemotherapy (planned epirubicin dose&#xD;
      &gt;300mg/m2) for breast cancer at four specialist centres in the North of England will be&#xD;
      invited to participate. 170 eligible patients will be randomised in a 1:1 ratio, to either&#xD;
      enalapril plus usual care or to usual care. Enalapril will be commenced prior to the first&#xD;
      anthracycline dose, titrated to a maximum tolerated dose, and continued during chemotherapy.&#xD;
      Chemotherapy will continue per usual care; typically six treatment cycles. Patients will have&#xD;
      a blood test performed at the end of each chemotherapy cycle to measure cardiac troponin, and&#xD;
      at one month following the last epirubicin dose. Investigators and patients will be blinded&#xD;
      to the troponin results. Patients will have an echocardiogram at baseline and following their&#xD;
      chemotherapy; they will be assessed in a blinded manner by a central Core Laboratory.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 4, 2017</start_date>
  <completion_date type="Anticipated">May 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2022</primary_completion_date>
  <phase>Phase 3</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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cardiac troponin T release</measure>
    <time_frame>One month after last dose of anthracycline</time_frame>
    <description>Cardiac troponin T release during anthracycline treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cardiac function</measure>
    <time_frame>One month after last dose of anthracycline</time_frame>
    <description>Cardiac function assessed by echocardiogram</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adherence to enalapril</measure>
    <time_frame>One month after last dose of anthracycline</time_frame>
    <description>Ability of participant to adhere to enalapril</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events / Reactions</measure>
    <time_frame>One month after last dose of anthracycline</time_frame>
    <description>Number and severity of Adverse Events and Reactions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anxiety or distress related to trial participation</measure>
    <time_frame>One month after last dose of anthracycline</time_frame>
    <description>Anxiety or distress related to trial participation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cancer and chemotherapy outcomes</measure>
    <time_frame>One month after last dose of anthracycline</time_frame>
    <description>Cancer and chemotherapy outcomes in the population under study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac troponin I release</measure>
    <time_frame>One month after last dose of anthracycline</time_frame>
    <description>cardiac troponin I release during anthracyline treatment</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">128</enrollment>
  <condition>Breast Cancer</condition>
  <condition>Non Hodgkin Lymphoma</condition>
  <arm_group>
    <arm_group_label>Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard care</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enalapril</intervention_name>
    <description>Enalapril is an Angiotensin Converting Enzyme (ACE) inhibitor which supresses the reninangiotensin-aldosterone system resulting in increased plasma renin activity and decreased aldosterone secretion</description>
    <arm_group_label>Intervention</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent.&#xD;
&#xD;
          -  Adult patients with histopathologically* confirmed breast carcinoma who have received&#xD;
             surgery for their breast cancer; planned to receive 6 cycles of EC 90 (total planned&#xD;
             dose 540mg/m2 epirubicin) or FEC 75 (total planned dose 450mg/m2 epirubicin) adjuvant&#xD;
             chemotherapy regimen. Patients with HER2+ breast cancer are eligible for inclusion.&#xD;
&#xD;
        OR&#xD;
&#xD;
          -  Adult patients with histopathologically confirmed non-Hodgkin lymphoma (NHL), planned&#xD;
             to receive 6 cycles of R-CHOP or CHOP (total planned dose 300mg/m2 doxorubicin)&#xD;
             chemotherapy**&#xD;
&#xD;
               -  Patients with HER2+ breast cancer are eligible for inclusion. ** Patients who&#xD;
                  will receive an alternative anti-CD20 monoclonal antibody are eligible (for&#xD;
                  example O-CHOP), as long as the total planned doxorubicin dose is ≥300mg/m2 over&#xD;
                  6 cycles&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Positive baseline cardiac troponin T (≥14ng/L);&#xD;
&#xD;
          -  known contraindication to ACE inhibitor e.g. renal artery stenosis, severe aortic&#xD;
             stenosis;&#xD;
&#xD;
          -  are taking, or have a previous intolerance to ACEI (e.g. angioedema);&#xD;
&#xD;
          -  patient already taking other agents acting on the renin-angiotensin-aldosterone system&#xD;
             e.g. Aliskiren, angiotensin receptor blockers (ARBs), Entresto (sacubitril/valsartan),&#xD;
             spironolactone, eplerenone;&#xD;
&#xD;
          -  LVEF &lt;50%*;&#xD;
&#xD;
          -  estimated GFR &lt; 30 mL/min/1.73m2 at baseline;&#xD;
&#xD;
          -  hyperkalaemia defined as serum potassium ≥5.5mmol/L;&#xD;
&#xD;
          -  symptomatic hypotension, or Systolic Blood Pressure &lt;100mmHg;&#xD;
&#xD;
          -  poorly-controlled hypertension (Blood Pressure &gt;160/100mmHg**, or ambulatory BP of&#xD;
             150/95mmHg);&#xD;
&#xD;
          -  previous myocardial infarction;&#xD;
&#xD;
          -  known metastatic breast cancer;&#xD;
&#xD;
          -  previous exposure to anthracycline chemotherapy;&#xD;
&#xD;
          -  are pregnant or breastfeeding;&#xD;
&#xD;
          -  previous Herceptin treatment or planned Herceptin treatment within four weeks&#xD;
             following anthracycline chemotherapy;&#xD;
&#xD;
          -  for patients of childbearing potential: refusal to use adequate contraception&#xD;
             throughout the trial;***&#xD;
&#xD;
          -  any other invasive cancer diagnosed and treated in the past 5 years;&#xD;
&#xD;
          -  symptomatic or severe asymptomatic radiation-induced cardiac disease;&#xD;
&#xD;
          -  judgement by the investigator that the patient has a prognosis of &lt; 1 year or are&#xD;
             unlikely to complete 6 cycles of chemotherapy;&#xD;
&#xD;
          -  judgement by the investigator that the patient is high risk for tumour lysis syndrome&#xD;
             (applicable only to NHL patients);&#xD;
&#xD;
          -  judgement by the Investigator that the patient should not participate in the study,&#xD;
             for example, if the patient is unlikely to comply with study procedures, restrictions,&#xD;
             and requirements.&#xD;
&#xD;
             *&lt;50% as defined by Simpson's biplane method; if absolute measurements are not&#xD;
             possible, then a visually normal assessment of LVEF is acceptable for inclusion.&#xD;
&#xD;
             **White coat hypertension is more common, and should be ruled out by an ambulatory&#xD;
             blood pressure monitor&#xD;
&#xD;
             ***Female patients between the ages of 18 and 50 will receive a pregnancy test at&#xD;
             baseline. Adequate methods of contraception are those that can achieve a failure rate&#xD;
             of less than&#xD;
&#xD;
             1% per year when used consistently and correctly, such methods include:&#xD;
&#xD;
          -  combined (estrogen and progestogen containing) hormonal contraception associated with&#xD;
             inhibition of ovulation&#xD;
&#xD;
               -  oral&#xD;
&#xD;
               -  intravaginal&#xD;
&#xD;
               -  transdermal&#xD;
&#xD;
          -  progestogen-only hormonal contraception associated with inhibition of ovulation&#xD;
&#xD;
               -  oral&#xD;
&#xD;
               -  injectable&#xD;
&#xD;
               -  implantable&#xD;
&#xD;
          -  intrauterine device (IUD)&#xD;
&#xD;
          -  intrauterine hormone-releasing system (IUS)&#xD;
&#xD;
          -  bilateral tubal occlusion&#xD;
&#xD;
          -  vasectomy/vasectomised partner&#xD;
&#xD;
          -  true sexual abstinence&#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>Victoria Hildreth</last_name>
    <role>Study Chair</role>
    <affiliation>Study Chair</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>David Austin</last_name>
    <phone>01642 850850</phone>
    <phone_ext>55909</phone_ext>
    <email>david.austin@nhs.net</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Victoria Hildreth</last_name>
    <phone>0191 208 5825</phone>
    <email>PROACT@ncl.ac.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>South Tees Hospitals NHS FT</name>
      <address>
        <city>Middlesbrough</city>
        <state>Teesside</state>
        <zip>TS4 3BW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>David Austin</last_name>
    </contact>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>August 24, 2017</study_first_submitted>
  <study_first_submitted_qc>August 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 29, 2017</study_first_posted>
  <last_update_submitted>October 20, 2022</last_update_submitted>
  <last_update_submitted_qc>October 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 24, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Enalapril</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03265574
org study id: 2016152
nct id: NCT03265574
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
PROACT will establish the effectiveness of the angiotensin-converting enzyme inhibitor (ACEI)
      enalapril maleate (enalapril) in preventing cardiotoxicity in patients with breast cancer and
      non-Hodgkin lymphoma undergoing adjuvant epirubicin-based chemotherapy.
PROACT is a phase 3 randomised, open label, blinded endpoint, superiority trial of enalapril
      to prevent anthracycline-induced in patients treated for breast cancer and lymphoma.

      Anthracyclines used in the treatment of breast cancer cause damage to heart muscle cells;
      this results in cell death (cardiotoxicity). In UK contemporary practice, epirubicin is the
      most frequently used anthracycline.

      Patients due to receive adjuvant anthracycline chemotherapy (planned epirubicin dose
      >300mg/m2) for breast cancer at four specialist centres in the North of England will be
      invited to participate. 170 eligible patients will be randomised in a 1:1 ratio, to either
      enalapril plus usual care or to usual care. Enalapril will be commenced prior to the first
      anthracycline dose, titrated to a maximum tolerated dose, and continued during chemotherapy.
      Chemotherapy will continue per usual care; typically six treatment cycles. Patients will have
      a blood test performed at the end of each chemotherapy cycle to measure cardiac troponin, and
      at one month following the last epirubicin dose. Investigators and patients will be blinded
      to the troponin results. Patients will have an echocardiogram at baseline and following their
      chemotherapy; they will be assessed in a blinded manner by a central Core Laboratory.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Single (Outcomes Assessor)
measure: Cardiac troponin T release
time frame: One month after last dose of anthracycline
description: Cardiac troponin T release during anthracycline treatment
measure: Cardiac function
time frame: One month after last dose of anthracycline
description: Cardiac function assessed by echocardiogram
measure: Adherence to enalapril
time frame: One month after last dose of anthracycline
description: Ability of participant to adhere to enalapril
measure: Adverse Events / Reactions
time frame: One month after last dose of anthracycline
description: Number and severity of Adverse Events and Reactions
measure: Anxiety or distress related to trial participation
time frame: One month after last dose of anthracycline
description: Anxiety or distress related to trial participation
measure: Cancer and chemotherapy outcomes
time frame: One month after last dose of anthracycline
description: Cancer and chemotherapy outcomes in the population under study
measure: Cardiac troponin I release
time frame: One month after last dose of anthracycline
description: cardiac troponin I release during anthracyline treatment
arm group label: Intervention
arm group type: Experimental
arm group label: Standard care
arm group type: No Intervention
intervention type: Drug
intervention name: Enalapril
description: Enalapril is an Angiotensin Converting Enzyme (ACE) inhibitor which supresses the reninangiotensin-aldosterone system resulting in increased plasma renin activity and decreased aldosterone secretion
arm group label: Intervention
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Victoria Hildreth
role: Study Chair
affiliation: Study Chair
last name: David Austin
phone: 01642 850850
phone ext: 55909
email: david.austin@nhs.net
last name: Victoria Hildreth
phone: 0191 208 5825
email: PROACT@ncl.ac.uk
facility: 
status: Recruiting
contact: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Breast Neoplasms
mesh term: Enalapril
sharing ipd: Undecided