<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/NCT01722851</url>
  </required_header>
  <id_info>
    <org_study_id>ICORG 10-11</org_study_id>
    <nct_id>NCT01722851</nct_id>
  </id_info>
  <brief_title>Circulating miRNAs.</brief_title>
  <official_title>Novel Breast Cancer Biomarkers and Their Use for Guiding and Monitoring Response to Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cancer Trials Ireland</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cancer Trials Ireland</source>
  <brief_summary>
    <textblock>
      To identify a panel of circulating miRNA markers which could help identify those breast&#xD;
      cancer patients who are most likely to respond well to neoadjuvant and adjuvant chemotherapy,&#xD;
      and indeed serve as an overall prognostic factor and stratify patients into risk categories&#xD;
      which would further guide their management. Similarly, the investigators aim to identify a&#xD;
      panel of circulating miRNA markers which could monitor patient's response to chemotherapy and&#xD;
      hormonal therapies. Ideally a suitable panel of markers would show significant changes in&#xD;
      expression level in good-responders whilst little or no change would be observed in miRNA&#xD;
      expression in non-responders.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Objectives:&#xD;
&#xD;
        1. To identify a panel of miRNAs, detectable in the circulation, which are altered in&#xD;
           breast cancer patients&#xD;
&#xD;
        2. To identify specific combinations of miRNAs ('signatures') which associate with breast&#xD;
           cancer intrinsic subtypes, and thereby could aid in prognostication and treatment&#xD;
           planning on an individual patient basis.&#xD;
&#xD;
      Secondary Objective:&#xD;
&#xD;
        1. To determine if systemic miRNA analysis can be used as a biomarker for monitoring&#xD;
           response to chemotherapy, in the neoadjuvant setting and in patients who present with&#xD;
           breast cancer recurrence and are treated with upfront chemotherapy and/or hormonal&#xD;
           therapy.&#xD;
&#xD;
           This is a prospective cohort studies, involving three study cohorts:&#xD;
&#xD;
           Cohort 1: All newly diagnosed breast cancer patients who are scheduled to undergo&#xD;
           neoadjuvant chemotherapy.&#xD;
&#xD;
           Cohort 2: All breast cancer patients who present with metastatic disease, disease&#xD;
           recurrence or progression, who are commencing up-front chemotherapy +/- hormonal&#xD;
           therapy.&#xD;
&#xD;
           Cohort 3: All breast cancer patients who present with metastatic disease who are&#xD;
           commencing hormonal therapy only.&#xD;
&#xD;
           Blood Sample&#xD;
&#xD;
           Blood Sampling - Cohort 1:&#xD;
&#xD;
           - Blood sample 1: at presentation before commencing neoadjuvant treatment.&#xD;
&#xD;
           - Blood sample 2: midway through their chemotherapy treatment (after 2nd cycle if they&#xD;
           are enrolled in a 4 cycle regimen, or after 4th cycle if they are prescribed an 8 week&#xD;
           regimen).&#xD;
&#xD;
           - Blood sample 3: post-chemotherapy (before surgery as applicable).&#xD;
&#xD;
           - Blood sample 4: 2 to 4 weeks after surgery, or 2 to 4 weeks post 3rd blood sampling if&#xD;
           patients do not undergo surgery.&#xD;
&#xD;
           - Blood sample 5: once during follow-up of 12 to 18 months after surgery or 12 to 18&#xD;
           months post 3rd blood sampling if patients do not undergo surgery.&#xD;
&#xD;
           Blood Sampling - Cohort 2:&#xD;
&#xD;
           - Pre-treatment blood sample: at presentation before commencing treatment.&#xD;
&#xD;
           - On study blood samples: taken at monthly (± 1 week) intervals for a period of 6 months&#xD;
           from date of pre-treatment blood sample, despite whether the patient is on treatment or&#xD;
           completed treatment.&#xD;
&#xD;
           On study blood sample 1: 1 month (± 1 week) from date of pre-treatment blood sample&#xD;
&#xD;
           On study blood sample 2: 2 months (± 1 week) from date of pre- treatment blood sample&#xD;
&#xD;
           On study blood sample 3: 3 months (± 1 week) from date of pre-treatment blood sample&#xD;
&#xD;
           On study blood sample 4: 4 months (± 1 week) from date of pre-treatment blood sample&#xD;
&#xD;
           On study blood sample 5: 5 months (± 1 week) from date of pre-treatment blood sample&#xD;
&#xD;
           On study blood sample 6: 6 months (± 1 week) from date of pre-treatment blood sample&#xD;
&#xD;
           - End of study blood sample: once during follow-up of 12 to 18 months from date of&#xD;
           pre-treatment blood sample or at the time of disease progression.&#xD;
&#xD;
           Blood Sampling - Cohort 3:&#xD;
&#xD;
           - Pre-treatment blood sample: at presentation before commencing treatment.&#xD;
&#xD;
           - On study blood samples: taken at the following time points despite whether the patient&#xD;
           is on treatment or completed treatment.&#xD;
&#xD;
           On study blood sample 1: 3 months (± 2 weeks) from date of pre-treatment blood sample On&#xD;
           study blood sample 2: 6 months (± 2 weeks) from date of pre-treatment blood sample On&#xD;
           study blood sample 3: 12 months (± 2 weeks) from date of pre-treatment blood sample&#xD;
&#xD;
           - End of study blood sample: 18 months (± 2 weeks) from date of pre-treatment blood&#xD;
           sample or at the time of disease progression.&#xD;
&#xD;
           Blood samples will be processed for miRNA analysis, which involves:&#xD;
&#xD;
      1. Lysis using Trizol 2. RNA isolation 3. Assessing concentration and integrity of RNA using&#xD;
      Nanodrop spectrophotometry 4. cDNA synthesis (using miRNA specific stem loop primers) 5. PCR&#xD;
      amplification and relative quantification (using miRNA specific probes)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 2011</start_date>
  <completion_date type="Actual">December 2021</completion_date>
  <primary_completion_date type="Actual">April 1, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Relationship between changes in a patients circulating miRNA expression levels over the course of their systemic therapy, and their response to that treatment.</measure>
    <time_frame>Up to week 66-92</time_frame>
    <description>For cohort 1, a patient's response to treatment will be determined using 3 standard parameters: clinical, radiological and pathological responses.&#xD;
For cohort 2 and 3, a patient's response to treatment will be evaluated using RECIST criteria version 1.1.&quot; For cohort 1, a patient's response to treatment will be determined using 3 standard parameters: clinical, radiological and pathological responses.&#xD;
For cohort 2 and 3, a patient's response to treatment will be evaluated using RECIST criteria version 1.1.&quot;</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Correlation of systemic miRNA levels with standard biomarkers of response</measure>
    <time_frame>Up to week 66-92</time_frame>
    <description>Standard bio markers of response include serum CEA and Ca15-3 levels</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Relationship between circulating miRNA profiles and patients' intrinsic subtype of breast cancer</measure>
    <time_frame>Up to week 66-92</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relationship between miRNA expression levels and other existing clinicopathological parameters.</measure>
    <time_frame>Up to week 66-92</time_frame>
    <description>Other existing clinicopathological parameters include: ER, PR and HER2 status, stage of disease,histological grade and size of the tumour, and the Nottingham Prognostic Index.</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">255</enrollment>
  <condition>Breast Cancer</condition>
  <condition>Newly Diagnosed Breast Cancer</condition>
  <condition>Recurrent Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <description>All newly diagnosed breast cancer patients who are scheduled to undergo neoadjuvant chemotherapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2</arm_group_label>
    <description>All breast cancer patients who present with metastatic disease, disease recurrence or progression, who are commencing up-front chemotherapy ± hormonal therapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3</arm_group_label>
    <description>All breast cancer patient who present with metastatic disease who are commencing hormonal therapy only.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Investigators aim to study two populations of breast cancer patients:&#xD;
&#xD;
          1. Patients undergoing neoadjuvant chemotherapy for breast cancer at tertiary referral&#xD;
             breast cancer centres in Ireland.&#xD;
&#xD;
             For GUH only: Additionally,investigators wish to evaluate miRNA expression levels in&#xD;
             patients' diagnostic core biopsies.&#xD;
&#xD;
          2. Investigators also wish to study the same panel of miRNAs in patients who present with&#xD;
             disease recurrence or disease progression, and who are commenced on systemic therapies&#xD;
             (hormonal and/or chemotherapy).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          1. Patient must meet the criteria for either:&#xD;
&#xD;
             Cohort 1: All patients with a new diagnosis of breast cancer, who are destined to&#xD;
             undergo neoadjuvant chemotherapy.&#xD;
&#xD;
             OR Cohort 2: All breast cancer patients who present with metastatic disease, disease&#xD;
             recurrence or progression who will receive up-front chemotherapy ± hormonal therapy.&#xD;
&#xD;
             OR Cohort 3: All breast cancer patient who present with metastatic disease who are&#xD;
             commencing hormonal therapy only.&#xD;
&#xD;
          2. Patients must be aged 18 years or over.&#xD;
&#xD;
          3. Patients must be able to give written informed consent.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
        All patients, who do not fulfil the inclusion criteria mentioned above.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Bon Secours Hospital</name>
      <address>
        <city>Cork</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beaumont Hospital</name>
      <address>
        <city>Dublin</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St James's Hospital</name>
      <address>
        <city>Dublin</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Galway</name>
      <address>
        <city>Galway</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Letterkenny General Hospital</name>
      <address>
        <city>Letterkenny</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sligo General Hospital</name>
      <address>
        <city>Sligo</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Midlands Regional Hospital Tullamore</name>
      <address>
        <city>Tullamore</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Ireland</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>October 24, 2012</study_first_submitted>
  <study_first_submitted_qc>November 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 7, 2012</study_first_posted>
  <last_update_submitted>April 4, 2023</last_update_submitted>
  <last_update_submitted_qc>April 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Breast Cancer</keyword>
  <keyword>miRNAs</keyword>
  <keyword>Newly diagnosed</keyword>
  <keyword>Recurrent</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <!-- 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/NCT01722851
org study id: ICORG 10-11
nct id: NCT01722851
lead sponsor: 
To identify a panel of circulating miRNA markers which could help identify those breast
      cancer patients who are most likely to respond well to neoadjuvant and adjuvant chemotherapy,
      and indeed serve as an overall prognostic factor and stratify patients into risk categories
      which would further guide their management. Similarly, the investigators aim to identify a
      panel of circulating miRNA markers which could monitor patient's response to chemotherapy and
      hormonal therapies. Ideally a suitable panel of markers would show significant changes in
      expression level in good-responders whilst little or no change would be observed in miRNA
      expression in non-responders.
Primary Objectives:

        1. To identify a panel of miRNAs, detectable in the circulation, which are altered in
           breast cancer patients

        2. To identify specific combinations of miRNAs ('signatures') which associate with breast
           cancer intrinsic subtypes, and thereby could aid in prognostication and treatment
           planning on an individual patient basis.

      Secondary Objective:

        1. To determine if systemic miRNA analysis can be used as a biomarker for monitoring
           response to chemotherapy, in the neoadjuvant setting and in patients who present with
           breast cancer recurrence and are treated with upfront chemotherapy and/or hormonal
           therapy.

           This is a prospective cohort studies, involving three study cohorts:

           Cohort 1: All newly diagnosed breast cancer patients who are scheduled to undergo
           neoadjuvant chemotherapy.

           Cohort 2: All breast cancer patients who present with metastatic disease, disease
           recurrence or progression, who are commencing up-front chemotherapy +/- hormonal
           therapy.

           Cohort 3: All breast cancer patients who present with metastatic disease who are
           commencing hormonal therapy only.

           Blood Sample

           Blood Sampling - Cohort 1:

           - Blood sample 1: at presentation before commencing neoadjuvant treatment.

           - Blood sample 2: midway through their chemotherapy treatment (after 2nd cycle if they
           are enrolled in a 4 cycle regimen, or after 4th cycle if they are prescribed an 8 week
           regimen).

           - Blood sample 3: post-chemotherapy (before surgery as applicable).

           - Blood sample 4: 2 to 4 weeks after surgery, or 2 to 4 weeks post 3rd blood sampling if
           patients do not undergo surgery.

           - Blood sample 5: once during follow-up of 12 to 18 months after surgery or 12 to 18
           months post 3rd blood sampling if patients do not undergo surgery.

           Blood Sampling - Cohort 2:

           - Pre-treatment blood sample: at presentation before commencing treatment.

           - On study blood samples: taken at monthly (± 1 week) intervals for a period of 6 months
           from date of pre-treatment blood sample, despite whether the patient is on treatment or
           completed treatment.

           On study blood sample 1: 1 month (± 1 week) from date of pre-treatment blood sample

           On study blood sample 2: 2 months (± 1 week) from date of pre- treatment blood sample

           On study blood sample 3: 3 months (± 1 week) from date of pre-treatment blood sample

           On study blood sample 4: 4 months (± 1 week) from date of pre-treatment blood sample

           On study blood sample 5: 5 months (± 1 week) from date of pre-treatment blood sample

           On study blood sample 6: 6 months (± 1 week) from date of pre-treatment blood sample

           - End of study blood sample: once during follow-up of 12 to 18 months from date of
           pre-treatment blood sample or at the time of disease progression.

           Blood Sampling - Cohort 3:

           - Pre-treatment blood sample: at presentation before commencing treatment.

           - On study blood samples: taken at the following time points despite whether the patient
           is on treatment or completed treatment.

           On study blood sample 1: 3 months (± 2 weeks) from date of pre-treatment blood sample On
           study blood sample 2: 6 months (± 2 weeks) from date of pre-treatment blood sample On
           study blood sample 3: 12 months (± 2 weeks) from date of pre-treatment blood sample

           - End of study blood sample: 18 months (± 2 weeks) from date of pre-treatment blood
           sample or at the time of disease progression.

           Blood samples will be processed for miRNA analysis, which involves:

      1. Lysis using Trizol 2. RNA isolation 3. Assessing concentration and integrity of RNA using
      Nanodrop spectrophotometry 4. cDNA synthesis (using miRNA specific stem loop primers) 5. PCR
      amplification and relative quantification (using miRNA specific probes)
observational model: Cohort
time perspective: Prospective
measure: Relationship between changes in a patients circulating miRNA expression levels over the course of their systemic therapy, and their response to that treatment.
time frame: Up to week 66-92
description: For cohort 1, a patient's response to treatment will be determined using 3 standard parameters: clinical, radiological and pathological responses.
For cohort 2 and 3, a patient's response to treatment will be evaluated using RECIST criteria version 1.1." For cohort 1, a patient's response to treatment will be determined using 3 standard parameters: clinical, radiological and pathological responses.
For cohort 2 and 3, a patient's response to treatment will be evaluated using RECIST criteria version 1.1."
measure: Correlation of systemic miRNA levels with standard biomarkers of response
time frame: Up to week 66-92
description: Standard bio markers of response include serum CEA and Ca15-3 levels
measure: Relationship between circulating miRNA profiles and patients' intrinsic subtype of breast cancer
time frame: Up to week 66-92
measure: Relationship between miRNA expression levels and other existing clinicopathological parameters.
time frame: Up to week 66-92
description: Other existing clinicopathological parameters include: ER, PR and HER2 status, stage of disease,histological grade and size of the tumour, and the Nottingham Prognostic Index.
arm group label: Cohort 1
description: All newly diagnosed breast cancer patients who are scheduled to undergo neoadjuvant chemotherapy
arm group label: Cohort 2
description: All breast cancer patients who present with metastatic disease, disease recurrence or progression, who are commencing up-front chemotherapy ± hormonal therapy
arm group label: Cohort 3
description: All breast cancer patient who present with metastatic disease who are commencing hormonal therapy only.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Ireland
responsible party type: Sponsor
mesh term: Breast Neoplasms