<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/NCT03790813</url>
  </required_header>
  <id_info>
    <org_study_id>H18-02581</org_study_id>
    <nct_id>NCT03790813</nct_id>
  </id_info>
  <brief_title>Informative Tools to Optimize Neoadjuvant Therapy in ER Positive, HER2 Negative Breast Cancers</brief_title>
  <acronym>ER</acronym>
  <official_title>Informative Tools to Optimize Neoadjuvant Therapy in ER Positive, HER2 Negative Breast Cancers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>British Columbia Cancer Agency</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Genomic Health®, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>British Columbia Cancer Agency</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>
      This study evaluates the addition of Ki-67, Oncotype DX and MRI in the treatment of early&#xD;
      stage breast cancer with neoadjuvant treatment. All enrolled patients will have Ki-67 and&#xD;
      Oncotype AND/OR an MRI before and after surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Based on what is known about the treatment of breast cancer, there are occasional advantages&#xD;
      to giving treatment before surgery. Some of these advantages can include shrinking a large&#xD;
      breast cancer to facilitate surgery, shrinking a breast cancer to allow breast conservation&#xD;
      (avoid a mastectomy), and evaluating how effective a treatment is in real-time, based on its&#xD;
      effect on the breast cancer.&#xD;
&#xD;
      When recommending treatment with hormone therapy and/or chemotherapy, doctors take into&#xD;
      consideration all the characteristics of a breast cancer. Over recent years, is has been&#xD;
      recognized that additional tests can help predict the behavior of a cancer and predict the&#xD;
      possible benefit of hormone therapy and/or chemotherapy. Because there is no way to identify&#xD;
      exactly who benefits from chemotherapy, many patients receive chemotherapy when they might&#xD;
      not need it.&#xD;
&#xD;
      This study involves the use of 2 separate tests. The first is called Ki-67 and is done using&#xD;
      a piece of tumour that is taken during a needle biopsy. The second, called the Oncotype DX,&#xD;
      is made by Genomic Health, Inc, located in Redwood, CA, USA. This test also uses a piece of&#xD;
      tumour that was retrieved during a needle biopsy. The pieces will be tested in a specialized&#xD;
      laboratory that can measure the levels of a specific set of genes in the tumour. The&#xD;
      laboratory that performs this test (Redwood, CA, USA) has been certified by federal and state&#xD;
      agencies in the United States to perform the test (called Oncotype DX). The results of the&#xD;
      test are turned into a score (called Recurrence Score) that has been used for patients&#xD;
      receiving treatment after surgery, but has not yet been used when treatment is given before&#xD;
      surgery.&#xD;
&#xD;
      The standard practice for this type of cancer is for the patient and their doctor to decide&#xD;
      whether they should receive chemotherapy in addition to hormone therapy or to take hormone&#xD;
      therapy alone, prior to surgery. The Ki-67 is inconsistently used in British Columbia prior&#xD;
      to surgery, but may be used routinely in other centers. Usually, the Oncotype DX test is not&#xD;
      available to aid in this decision outside of a research study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">January 7, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2019</primary_completion_date>
  <phase>N/A</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>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Feasibility of neoajduvant Ki-67 and Oncotype DX, defined as &gt;=75% enrollment rate for all screened patients</measure>
    <time_frame>1 month</time_frame>
    <description>• Technical feasibility of obtaining Ki-67 and Oncotype DX assay from a core biopsy sample in &gt;= 75% of samples tested, prior to the initiation of systemic treatment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Turnaround time of Ki-67 and Oncotype DX, defined as time from patient consent to date results are obtained</measure>
    <time_frame>1 month</time_frame>
    <description>Turnaround time will be defined as:&#xD;
Time from patient consent to reporting of the Ki-67 and Oncotype DX</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility of MRI prior to neoadjuvant systemic treatment, defined as &gt;=75% of patients who receive an MRI before the start of neoadjuvant treatment</measure>
    <time_frame>6 months</time_frame>
    <description>• Practical feasibility of obtaining serial MRIs with the existing means, resources and booking circumstances in &gt;=75% of cases prior to the initiation of systemic therapy and surgical resection</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Turnaround time of MRI prior to neoadjuvant systemic treatment, defined as time from patient consent to date of 1st MRI</measure>
    <time_frame>6 months</time_frame>
    <description>Turnaround time will be defined as:&#xD;
• Time from patient consent to pre-treatment (baseline) MRI</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Correlation of Ki-67 and Oncotype DX to each other and to the outcome of neoadjuvant systemic treatment.</measure>
    <time_frame>6 months</time_frame>
    <description>To characterize how the results of the Ki-67 Oncotype DX assay relate to the outcome of neoadjuvant systemic treatment and whether the results correlate to each other (Ki-67 and Oncotype DX).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Predictive association of Ki-67 and Oncotype to invasive locoregional or systemic relapse</measure>
    <time_frame>5 years</time_frame>
    <description>• Time from study enrollment to the development of invasive locoregional or systemic breast cancer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Predictive association of Ki-67 and Oncotype to overall survival</measure>
    <time_frame>5 years</time_frame>
    <description>• Time from enrollment to death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Impact of serial MRI on changes to surgical planning</measure>
    <time_frame>6 months</time_frame>
    <description>Changes from original to final surgical plan.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation of serial MRI to clinical and pathological response</measure>
    <time_frame>6 months</time_frame>
    <description>Characterize how the results of serial MRIs affect surgical planning and how the radiological response relates to clinical response and pathological response.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient reported outcomes assessed by questionnaire</measure>
    <time_frame>6 months</time_frame>
    <description>Patient reported outcomes assessed with a questionnaire exploring decisional conflict.&#xD;
9 questions are asked of patients regarding the MRI results and its impact on decision making. The scale is a 5 point scale, ranging from strongly disagree (1) to strongly agree (5). Results will be reported qualitatively.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Eligible patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Intervention 1</intervention_name>
    <description>Ki-67 and Oncotype DX® will be performed on the baseline core biopsy specimen prior to initiation of neoadjuvant systemic therapy.</description>
    <arm_group_label>Eligible patients</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Intervention 2</intervention_name>
    <description>MRI will be performed prior to initiation of neoadjuvant systemic therapy and at the end of treatment.</description>
    <arm_group_label>Eligible patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patient must be between the ages (inclusive) of 18-89.&#xD;
&#xD;
          2. Patient has adequate performance status (PS ECOG 0,1 or Karnofsky performance status&#xD;
             ≥70) and is a medically fit candidate for treatment of their cancer with systemic&#xD;
             chemotherapy and/or hormonal therapy with no contra-indications to both systemic&#xD;
             therapy options.&#xD;
&#xD;
          3. Patient is medically fit enough to be a surgical candidate.&#xD;
&#xD;
          4. Patient must be able to give informed consent directly or through the assistance of an&#xD;
             interpreter.&#xD;
&#xD;
          5. Pathological confirmation of breast cancer by core biopsy.&#xD;
&#xD;
          6. Ductal or lobular breast cancer.&#xD;
&#xD;
          7. Breast cancer with a primary tumour (clinically selected T2-T4) OR clinically node&#xD;
             positive.&#xD;
&#xD;
          8. Breast cancer is clinically palpable either in the breast, axilla or other nodal site.&#xD;
&#xD;
          9. ER positive by IHC (Allred &gt;=4).&#xD;
&#xD;
         10. Her2Neu negative by IHC (0 or 1+) or FISH by current ASCO/CAP guidelines.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient is a male with breast cancer.&#xD;
&#xD;
          2. Patients have ER negative tumors (ER-) by local or central BCCA assessment.&#xD;
&#xD;
          3. Patients have HER2 positive tumors by local or central BCCA assessment.&#xD;
&#xD;
          4. Patients have known metastatic breast cancer or develop metastatic disease prior to&#xD;
             surgery.&#xD;
&#xD;
          5. Patients are unable to give consent or understand written language.&#xD;
&#xD;
          6. Patients with poor performance status (ECOG 2-4) in whom consideration of neoadjuvant&#xD;
             chemotherapy OR hormonal therapy would be contraindicated.&#xD;
&#xD;
          7. Patients who are not fit enough to be a surgical candidate.&#xD;
&#xD;
          8. Pregnant women in whom consideration of neoadjuvant chemotherapy or neoadjuvant&#xD;
             hormonal therapy would be contraindicated.&#xD;
&#xD;
          9. Patients who receive less than 2 weeks of neoadjuvant systemic therapy.&#xD;
&#xD;
         10. Patients who have not undergone surgical resection 12 months after enrollment.&#xD;
&#xD;
        For intervention 1 only:&#xD;
&#xD;
          1. Patients with tumors that on GHI central pathological review appears inadequate for&#xD;
             the Oncotype DX® assay.&#xD;
&#xD;
          2. Patients with tumors that on BCCA pathological review appears inadequate for Ki-67&#xD;
             immunohistochemistry.&#xD;
&#xD;
        For intervention 2 only:&#xD;
&#xD;
        1. Patients with a pacemaker or contra-indication to MRI.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>89 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stephen Chia, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>BCCA</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Nathalie LeVasseur, MD</last_name>
    <phone>604-877-6000x2734</phone>
    <email>nathalie.levasseur@bccancer.bc.ca</email>
  </overall_contact>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>November 30, 2018</study_first_submitted>
  <study_first_submitted_qc>December 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">January 2, 2019</study_first_posted>
  <last_update_submitted>December 28, 2018</last_update_submitted>
  <last_update_submitted_qc>December 28, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 2, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>British Columbia Cancer Agency</investigator_affiliation>
    <investigator_full_name>Stephen Chia</investigator_full_name>
    <investigator_title>Chair- British Columbia Breast Tumour Group</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03790813
org study id: H18-02581
nct id: NCT03790813
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study evaluates the addition of Ki-67, Oncotype DX and MRI in the treatment of early
      stage breast cancer with neoadjuvant treatment. All enrolled patients will have Ki-67 and
      Oncotype AND/OR an MRI before and after surgery.
Based on what is known about the treatment of breast cancer, there are occasional advantages
      to giving treatment before surgery. Some of these advantages can include shrinking a large
      breast cancer to facilitate surgery, shrinking a breast cancer to allow breast conservation
      (avoid a mastectomy), and evaluating how effective a treatment is in real-time, based on its
      effect on the breast cancer.

      When recommending treatment with hormone therapy and/or chemotherapy, doctors take into
      consideration all the characteristics of a breast cancer. Over recent years, is has been
      recognized that additional tests can help predict the behavior of a cancer and predict the
      possible benefit of hormone therapy and/or chemotherapy. Because there is no way to identify
      exactly who benefits from chemotherapy, many patients receive chemotherapy when they might
      not need it.

      This study involves the use of 2 separate tests. The first is called Ki-67 and is done using
      a piece of tumour that is taken during a needle biopsy. The second, called the Oncotype DX,
      is made by Genomic Health, Inc, located in Redwood, CA, USA. This test also uses a piece of
      tumour that was retrieved during a needle biopsy. The pieces will be tested in a specialized
      laboratory that can measure the levels of a specific set of genes in the tumour. The
      laboratory that performs this test (Redwood, CA, USA) has been certified by federal and state
      agencies in the United States to perform the test (called Oncotype DX). The results of the
      test are turned into a score (called Recurrence Score) that has been used for patients
      receiving treatment after surgery, but has not yet been used when treatment is given before
      surgery.

      The standard practice for this type of cancer is for the patient and their doctor to decide
      whether they should receive chemotherapy in addition to hormone therapy or to take hormone
      therapy alone, prior to surgery. The Ki-67 is inconsistently used in British Columbia prior
      to surgery, but may be used routinely in other centers. Usually, the Oncotype DX test is not
      available to aid in this decision outside of a research study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Feasibility of neoajduvant Ki-67 and Oncotype DX, defined as >=75% enrollment rate for all screened patients
time frame: 1 month
description: • Technical feasibility of obtaining Ki-67 and Oncotype DX assay from a core biopsy sample in >= 75% of samples tested, prior to the initiation of systemic treatment.
measure: Turnaround time of Ki-67 and Oncotype DX, defined as time from patient consent to date results are obtained
time frame: 1 month
description: Turnaround time will be defined as:
Time from patient consent to reporting of the Ki-67 and Oncotype DX
measure: Feasibility of MRI prior to neoadjuvant systemic treatment, defined as >=75% of patients who receive an MRI before the start of neoadjuvant treatment
time frame: 6 months
description: • Practical feasibility of obtaining serial MRIs with the existing means, resources and booking circumstances in >=75% of cases prior to the initiation of systemic therapy and surgical resection
measure: Turnaround time of MRI prior to neoadjuvant systemic treatment, defined as time from patient consent to date of 1st MRI
time frame: 6 months
description: Turnaround time will be defined as:
• Time from patient consent to pre-treatment (baseline) MRI
measure: Correlation of Ki-67 and Oncotype DX to each other and to the outcome of neoadjuvant systemic treatment.
time frame: 6 months
description: To characterize how the results of the Ki-67 Oncotype DX assay relate to the outcome of neoadjuvant systemic treatment and whether the results correlate to each other (Ki-67 and Oncotype DX).
measure: Predictive association of Ki-67 and Oncotype to invasive locoregional or systemic relapse
time frame: 5 years
description: • Time from study enrollment to the development of invasive locoregional or systemic breast cancer.
measure: Predictive association of Ki-67 and Oncotype to overall survival
time frame: 5 years
description: • Time from enrollment to death from any cause.
measure: Impact of serial MRI on changes to surgical planning
time frame: 6 months
description: Changes from original to final surgical plan.
measure: Correlation of serial MRI to clinical and pathological response
time frame: 6 months
description: Characterize how the results of serial MRIs affect surgical planning and how the radiological response relates to clinical response and pathological response.
measure: Patient reported outcomes assessed by questionnaire
time frame: 6 months
description: Patient reported outcomes assessed with a questionnaire exploring decisional conflict.
9 questions are asked of patients regarding the MRI results and its impact on decision making. The scale is a 5 point scale, ranging from strongly disagree (1) to strongly agree (5). Results will be reported qualitatively.
arm group label: Eligible patients
arm group type: Experimental
intervention type: Diagnostic Test
intervention name: Intervention 1
description: Ki-67 and Oncotype DX® will be performed on the baseline core biopsy specimen prior to initiation of neoadjuvant systemic therapy.
arm group label: Eligible patients
intervention type: Diagnostic Test
intervention name: Intervention 2
description: MRI will be performed prior to initiation of neoadjuvant systemic therapy and at the end of treatment.
arm group label: Eligible patients
criteria: 
gender: Female
gender based: Yes
minimum age: 18 Years
maximum age: 89 Years
healthy volunteers: No
last name: Stephen Chia, MD
role: Principal Investigator
affiliation: BCCA
last name: Nathalie LeVasseur, MD
phone: 604-877-6000x2734
email: nathalie.levasseur@bccancer.bc.ca
responsible party type: Principal Investigator
investigator affiliation: British Columbia Cancer Agency
investigator full name: Stephen Chia
investigator title: Chair- British Columbia Breast Tumour Group
mesh term: Breast Neoplasms
sharing ipd: No