<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/NCT03749421</url>
  </required_header>
  <id_info>
    <org_study_id>18-281</org_study_id>
    <nct_id>NCT03749421</nct_id>
  </id_info>
  <brief_title>Prospective Study of the Prosigna Assay on Neoadjuvant Clinical Decision-making in Women With HR+/Her2- Breast Cancer</brief_title>
  <official_title>Prospective Study of the Prosigna Assay on Neoadjuvant Clinical Decision-making in Women With HR+/Her2- Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dana-Farber Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>NanoString Technologies, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Dana-Farber Cancer Institute</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 research study is evaluating a genomic analysis called Predictor Analysis of Microarray&#xD;
      50 (PAM50, by Prosigna®) as a tool to possibly guide the participant and the treating&#xD;
      physician to choose the most personalized pre-operative treatment for breast cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      As the investigators understanding of how ER-positive breast cancer (a type of cancer in&#xD;
      which the cells need the hormone estrogen to grow) improves, more treatment decisions are&#xD;
      being tailored to an individual's unique genetic makeup. National medical guidelines now&#xD;
      include the routine use of tumor profiling tests, like the Prosigna® assay, which look at the&#xD;
      gene activity of a person's cancer cells to determine the likely outcome or course of a&#xD;
      disease (prognosis) and predict the benefit of chemotherapy or endocrine therapy after breast&#xD;
      surgery.&#xD;
&#xD;
      Currently, the Prosigna® assay (also called PAM-50) is FDA approved as a tool that physicians&#xD;
      can use to help make decisions about a patient's treatment after their breast surgery. In&#xD;
      these cases, physicians run this test using tumor tissue from a patient's breast surgery.&#xD;
      However, the Prosigna® assay is not approved for use preoperatively, or before surgery.&#xD;
&#xD;
      Previous studies showed that the Prosigna® assay was able to identify tumor types that were&#xD;
      more likely to benefit from treatment before surgery (whether it's hormonal therapy or&#xD;
      chemotherapy). In this study, the investigators will use tumor tissue from the participant's&#xD;
      biopsy to run the Prosigna® assay. The test may give both the participant and the&#xD;
      investigators more information about the best possible treatment option for the participant&#xD;
      before surgery.&#xD;
&#xD;
      This study is being done to determine how Prosigna® assay results may affect the physician's&#xD;
      choice of treatment before surgery and how well patients understand the test and its&#xD;
      implications.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 21, 2019</start_date>
  <completion_date type="Anticipated">January 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>The extent to which the Prosigna test results will change physician's pre-test decision regarding neoadjuvant treatment of patients with stage II-III ER/PR+, HER2-negative breast cancer</measure>
    <time_frame>2 years</time_frame>
    <description>Questionnaires will be used to record neoadjuvant treatment decisions pre- and post-test. Data will be summarized in a contingency table, and the extent to which decisions changed will be estimated as the proportion of discordant responses and reported with a two-sided exact 95% confidence interval.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The association of pCR/RCB following neoadjuvant therapy with Risk of recurrence (ROR).</measure>
    <time_frame>2 years</time_frame>
    <description>The association of the Prosigna test results to pathologic outcomes will be explored marginally in all patients who receive neoadjuvant treatment, and non-parametric Wilcoxon rank sum and Spearman test of correlation with two-sided alpha = 0.05 will be used to make inferences. Non-linear spline regression techniques will be used to explore the relationship between pre-treatment molecular phenotypes of response to neoadjuvant treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To assess if treatment change was based on ROR score, intrinsic subtype or both</measure>
    <time_frame>2 years</time_frame>
    <description>Non-linear spline regression techniques will be used to explore the relationship between pre-treatment molecular phenotypes and response to neoadjuvant treatment. On the &quot;Post-Prosigna Physician Questionnaire&quot; physicians will be asked which of these item (ROR score, instrinsic subtype, or both) contributed to their neoadjuvant treatment decision-making.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate physicians' confidence in their therapy before and after the test</measure>
    <time_frame>2 years</time_frame>
    <description>Physicians will complete pre-test and post-test questionnaires that measure their confidence at each timepoint. The pre-test questionnaire will examine the percentage of physicians who are confident about their treatment recommendation. The same questions about confidence in diagnosis and treatment will be realized after Prosigna results and rates will be compared.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate patients' confidence in their therapy before and after the test</measure>
    <time_frame>2 years</time_frame>
    <description>Patients will complete pre-test and post-test questionnaires to measure their confidence at each timepoint. The pre-test questionnaire will examine the percentage of patients who understand their diagnosis and how Prosigna works and who are confident in treatment recommendation. The same question about diagnosis and treatment will be realized after Prosigna results and rates will be compared.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Prosigna Assay</arm_group_label>
    <description>Biopsy specimen will be subject to molecular profiling via the Prosigna PAM-50 assay&#xD;
The results of Prosigna assay will be provided to the study team in a standardized report.&#xD;
This report will include the patient's intrinsic subtype, ROR score, and general risk (high, intermediate, low).</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Prosigna PAM-50 assay</intervention_name>
    <description>Looks at the gene activity of a person's cancer cells to determine the likely outcome or course of a disease (prognosis) and predict the benefit of chemotherapy or endocrine therapy after breast surgery</description>
    <arm_group_label>Prosigna Assay</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients that are considered possible candidates for neoadjuvant treatment, irrespective&#xD;
        whether chemotherapy or endocrine therapy, by clinical-pathologic features.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients pre- or post-menopausal must have histologically confirmed early&#xD;
             stage/locally advanced invasive breast cancer&#xD;
&#xD;
          -  ER or PR ≥ 1% by immunohistochemistry (IHC)&#xD;
&#xD;
          -  HER2-negative status, according to guidelines by ASCO CAP guidelines:&#xD;
&#xD;
        https://www.asco.org/practice-guidelines/quality-guidelines/guidelines/breast-cancer#/9751&#xD;
&#xD;
          -  Tumor size ≥ 0.5cm (clinical or radiographic measurements)&#xD;
&#xD;
          -  Any nodal status allowed&#xD;
&#xD;
          -  Age &gt; 18 years old&#xD;
&#xD;
          -  Felt to be a possible candidate for neoadjuvant systemic therapy by their treating&#xD;
             physician&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  ER-negative and PR-negative invasive breast cancer (&lt; 1% by IHC)&#xD;
&#xD;
          -  Known metastatic disease&#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>Sara Tolaney, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dana-Farber Cancer Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sara Tolaney, MD</last_name>
    <phone>617-632-2335</phone>
    <email>Sara_Tolaney@dfci.harvard.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sara Tolaney, MD</last_name>
      <phone>617-632-2335</phone>
      <email>Sara_Tolaney@dfci.harvard.edu</email>
    </contact>
    <investigator>
      <last_name>Sara Tolaney, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>October 19, 2018</study_first_submitted>
  <study_first_submitted_qc>November 17, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 21, 2018</study_first_posted>
  <last_update_submitted>January 9, 2023</last_update_submitted>
  <last_update_submitted_qc>January 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dana-Farber Cancer Institute</investigator_affiliation>
    <investigator_full_name>Sara Tolaney, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Breast Cancer</keyword>
  <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/NCT03749421
org study id: 18-281
nct id: NCT03749421
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This research study is evaluating a genomic analysis called Predictor Analysis of Microarray
      50 (PAM50, by Prosigna®) as a tool to possibly guide the participant and the treating
      physician to choose the most personalized pre-operative treatment for breast cancer.
As the investigators understanding of how ER-positive breast cancer (a type of cancer in
      which the cells need the hormone estrogen to grow) improves, more treatment decisions are
      being tailored to an individual's unique genetic makeup. National medical guidelines now
      include the routine use of tumor profiling tests, like the Prosigna® assay, which look at the
      gene activity of a person's cancer cells to determine the likely outcome or course of a
      disease (prognosis) and predict the benefit of chemotherapy or endocrine therapy after breast
      surgery.

      Currently, the Prosigna® assay (also called PAM-50) is FDA approved as a tool that physicians
      can use to help make decisions about a patient's treatment after their breast surgery. In
      these cases, physicians run this test using tumor tissue from a patient's breast surgery.
      However, the Prosigna® assay is not approved for use preoperatively, or before surgery.

      Previous studies showed that the Prosigna® assay was able to identify tumor types that were
      more likely to benefit from treatment before surgery (whether it's hormonal therapy or
      chemotherapy). In this study, the investigators will use tumor tissue from the participant's
      biopsy to run the Prosigna® assay. The test may give both the participant and the
      investigators more information about the best possible treatment option for the participant
      before surgery.

      This study is being done to determine how Prosigna® assay results may affect the physician's
      choice of treatment before surgery and how well patients understand the test and its
      implications.
observational model: Other
time perspective: Prospective
measure: The extent to which the Prosigna test results will change physician's pre-test decision regarding neoadjuvant treatment of patients with stage II-III ER/PR+, HER2-negative breast cancer
time frame: 2 years
description: Questionnaires will be used to record neoadjuvant treatment decisions pre- and post-test. Data will be summarized in a contingency table, and the extent to which decisions changed will be estimated as the proportion of discordant responses and reported with a two-sided exact 95% confidence interval.
measure: The association of pCR/RCB following neoadjuvant therapy with Risk of recurrence (ROR).
time frame: 2 years
description: The association of the Prosigna test results to pathologic outcomes will be explored marginally in all patients who receive neoadjuvant treatment, and non-parametric Wilcoxon rank sum and Spearman test of correlation with two-sided alpha = 0.05 will be used to make inferences. Non-linear spline regression techniques will be used to explore the relationship between pre-treatment molecular phenotypes of response to neoadjuvant treatment.
measure: To assess if treatment change was based on ROR score, intrinsic subtype or both
time frame: 2 years
description: Non-linear spline regression techniques will be used to explore the relationship between pre-treatment molecular phenotypes and response to neoadjuvant treatment. On the "Post-Prosigna Physician Questionnaire" physicians will be asked which of these item (ROR score, instrinsic subtype, or both) contributed to their neoadjuvant treatment decision-making.
measure: To evaluate physicians' confidence in their therapy before and after the test
time frame: 2 years
description: Physicians will complete pre-test and post-test questionnaires that measure their confidence at each timepoint. The pre-test questionnaire will examine the percentage of physicians who are confident about their treatment recommendation. The same questions about confidence in diagnosis and treatment will be realized after Prosigna results and rates will be compared.
measure: To evaluate patients' confidence in their therapy before and after the test
time frame: 2 years
description: Patients will complete pre-test and post-test questionnaires to measure their confidence at each timepoint. The pre-test questionnaire will examine the percentage of patients who understand their diagnosis and how Prosigna works and who are confident in treatment recommendation. The same question about diagnosis and treatment will be realized after Prosigna results and rates will be compared.
arm group label: Prosigna Assay
description: Biopsy specimen will be subject to molecular profiling via the Prosigna PAM-50 assay
The results of Prosigna assay will be provided to the study team in a standardized report.
This report will include the patient's intrinsic subtype, ROR score, and general risk (high, intermediate, low).
intervention type: Other
intervention name: Prosigna PAM-50 assay
description: Looks at the gene activity of a person's cancer cells to determine the likely outcome or course of a disease (prognosis) and predict the benefit of chemotherapy or endocrine therapy after breast surgery
arm group label: Prosigna Assay
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sara Tolaney, MD
role: Principal Investigator
affiliation: Dana-Farber Cancer Institute
last name: Sara Tolaney, MD
phone: 617-632-2335
email: Sara_Tolaney@dfci.harvard.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Dana-Farber Cancer Institute
investigator full name: Sara Tolaney, MD
investigator title: Principal Investigator
mesh term: Breast Neoplasms
sharing ipd: No