<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/NCT02239315</url>
  </required_header>
  <id_info>
    <org_study_id>495462</org_study_id>
    <nct_id>NCT02239315</nct_id>
  </id_info>
  <brief_title>Study of Tumor RNA Disruption Assay™ (RDA)</brief_title>
  <acronym>RnaDx</acronym>
  <official_title>Study of Tumor RNA Disruption Assay™ (RDA) and Its Association With a Response to Neoadjuvant Chemotherapy in Breast Cancer - A Prospective Mixed-Methods Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Toronto</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University Health Network, Toronto</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Toronto</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to find out if the pathological complete response (pCR) to&#xD;
      chemotherapy given before surgery (neoadjuvant chemotherapy) could be predicted by the&#xD;
      evaluation of the RNA (ribonucleic acids) disruption pattern (RNA Disruption Assay or RDA&#xD;
      score) obtained from a biopsy of the tumor 7 - 14 days after the first, second and third&#xD;
      cycles of chemotherapy treatment. If we can determine the optimal time during neoadjuvant&#xD;
      chemotherapy to measure the RDA score for the prediction of pCR, we can optimize breast&#xD;
      cancer management.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      When administering neoadjuvant chemotherapy, the current practice of monitoring response to&#xD;
      treatment is by measuring the size of the breast tumor after each cycle of chemotherapy. The&#xD;
      drawback to this method is, it will take several weeks before we can actually measure a&#xD;
      significant change in size; and the initial response to chemotherapy is often evident as a&#xD;
      softening of the tumor without an apparent decrease of the tumor size. Finding a reliable way&#xD;
      to identify early response to chemotherapy would be helpful to enable matching of&#xD;
      chemotherapy to an individual's need.&#xD;
&#xD;
      In a previous trial of breast cancer treated with neoadjuvant chemotherapy, researchers have&#xD;
      identified that the pCR to a full treatment of chemotherapy could be predicted by the change&#xD;
      in RNA pattern obtained from a biopsy of the tumor half way through the chemotherapy course.&#xD;
      [Parissenti et al. 2010] The purpose of this study is to determine if we can predict the pCR&#xD;
      to neoadjuvant chemotherapy by examining the pattern of RNA disruption (RNA Disruption Assay&#xD;
      or RDA score) from breast biopsy tissue obtained 7 to 14 days after the first, second and&#xD;
      third cycle of chemotherapy. If we can determine the optimal time during neoadjuvant&#xD;
      chemotherapy to measure the RDA score for the prediction of pCR, we can optimize breast&#xD;
      cancer management. For example, if RDA score can identify non-responders earlier, we can&#xD;
      switch to other chemotherapy agents and reduce the exposure to the unnecessary side-effects&#xD;
      of ineffective treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Lack of funding&#xD;
  </why_stopped>
  <start_date>December 2015</start_date>
  <completion_date type="Actual">May 2017</completion_date>
  <primary_completion_date type="Actual">May 2017</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>The association between RDA score and pathological complete response (pCR)</measure>
    <time_frame>An expected average of 6 months</time_frame>
    <description>The association between tumor RDA score measured 7-14 days after the first, second and third cycles of chemotherapy and the pCR to neoadjuvant chemotherapy will be evaluated. pCR is defined as no evidence of invasive carcinoma in the breast and lymph nodes (ypT0/Tis ypN0/N0itc) on histology at the time of surgery (lumpectomy or mastectomy).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The prognostic ability of RDA score</measure>
    <time_frame>An expected average of 6 months</time_frame>
    <description>The capacity of RDA score to predict pCR to neoadjuvant chemotherapy will be assessed by exploring for a cut point on the RDA score to differentiate subjects with a high likelihood of achieving pCR versus those who are less likely to achieve pCR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The association between RDA score and clinical response (cR)</measure>
    <time_frame>An expected average of 6 months</time_frame>
    <description>The association between tumor RDA score measured 7-14 days after the first, second and third cycles of chemotherapy and clinical response to neoadjuvant chemotherapy treatment will be evaluated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients' perception of fine needle aspiration biopsy (FNAB) and of breast cancer care</measure>
    <time_frame>An expected average of 12 months</time_frame>
    <description>We shall seek to understand the experiences of patients with the FNAB procedure and with the cancer care they received while participating in the study by conducting qualitative interviews of study subjects.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The cost-effectiveness of using RDA score</measure>
    <time_frame>An expected average of 6 months</time_frame>
    <description>The cost-effectiveness of using RDA score to guide neoadjuvant chemotherapy will be evaluated by measuring the cost-effectiveness of monitoring pCR to neoadjuvant chemotherapy through the RDA score and in modifying the neoadjuvant chemotherapy regimen for non-pCR patients accordingly.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The association between RDA score and Disease-Free Survival (DFS)</measure>
    <time_frame>An expected average of 5 years</time_frame>
    <description>The association between tumor RDA score measured 7-14 days after the first, second and third cycles of chemotherapy and DFS will be evaluated. DFS will be measured as the time from patient's enrollment to the event of cancer metastasis or recurrence, or death, whatever comes first.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Breast Neoplasms</condition>
  <arm_group>
    <arm_group_label>Tumor RNA Disruption Assay™ (RDA)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tumor RNA Disruption Assay™ (RDA) to generate RDA score from fine needle aspiration biopsy samples of breast cancer obtained 7-14 days after the first, second and third cycles of neoadjuvant chemotherapy; and, if there is a change of chemotherapy regimen, after the first cycle of the new chemotherapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Tumor RNA Disruption Assay™ (RDA)</intervention_name>
    <description>Tumor RNA Disruption Assay™ (RDA) to generate RDA score from fine needle aspiration biopsy samples of breast cancer obtained 7-14 days after the first, second and third cycles of neoadjuvant chemotherapy; and, if there is a change of chemotherapy regimen, after the first cycle of the new chemotherapy.</description>
    <arm_group_label>Tumor RNA Disruption Assay™ (RDA)</arm_group_label>
    <other_name>Biomarker</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female,18 years or older;&#xD;
&#xD;
          -  Able to read and write in English:&#xD;
&#xD;
          -  With palpable cancer &gt; 2cm (T2, T3) on clinical examination or clinical diagnosis of&#xD;
             locally advanced breast cancer (LABC) (T3 or T4; or N2 or N3, according to TNM cancer&#xD;
             staging including inflammatory breast cancer);&#xD;
&#xD;
          -  Must have histological proof of breast cancer (invasive ductal or infiltrating&#xD;
             lobular);&#xD;
&#xD;
          -  Scheduled to receive neoadjuvant chemotherapy as part of their treatment plan;&#xD;
&#xD;
          -  Agree to have FNAB after the first, second and third cycle of chemotherapy, and if the&#xD;
             chemotherapy regimen is changed, an additional FNAB after the first cycle of the new&#xD;
             chemotherapy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who have had surgery, neoadjuvant chemotherapy or radiotherapy for the&#xD;
             current breast cancer;&#xD;
&#xD;
          -  Subjects who are pregnant or breast feeding;&#xD;
&#xD;
          -  Subjects with Stage IV breast cancer;&#xD;
&#xD;
          -  Psychiatric or addictive disorders that may limit the ability to give informed consent&#xD;
             or complete the trial.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Murray Krahn, MD,MSc,FRCPC</last_name>
    <role>Principal Investigator</role>
    <affiliation>Director of THETA Collaborative, the F. Norman Hughes Chair in Pharmacoeconomics and Social and Administrative Pharmacy Division Head in the Faculty of Pharmacy, Professor at the University of Toronto</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hamilton Health Sciences Juravinski Cancer Centre</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8V 5C2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southlake Regional Health Centre</name>
      <address>
        <city>Newmarket</city>
        <state>Ontario</state>
        <zip>L3Y 2P9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sunnybrook Health Sciences Odette Cancer Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4N 3M5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Michael's Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5B 1W8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Parissenti AM, Chapman JA, Kahn HJ, Guo B, Han L, O'Brien P, Clemons MP, Jong R, Dent R, Fitzgerald B, Pritchard KI, Shepherd LE, Trudeau ME. Association of low tumor RNA integrity with response to chemotherapy in breast cancer patients. Breast Cancer Res Treat. 2010 Jan;119(2):347-56. doi: 10.1007/s10549-009-0531-x.</citation>
    <PMID>19771508</PMID>
  </reference>
  <reference>
    <citation>Schroeder A, Mueller O, Stocker S, Salowsky R, Leiber M, Gassmann M, Lightfoot S, Menzel W, Granzow M, Ragg T. The RIN: an RNA integrity number for assigning integrity values to RNA measurements. BMC Mol Biol. 2006 Jan 31;7:3. doi: 10.1186/1471-2199-7-3.</citation>
    <PMID>16448564</PMID>
  </reference>
  <reference>
    <citation>Guidance for Industry- Pathologic Complete Response in Neoadjuvant Treatment of High-Risk Early-Stage Breast Cancer: Use as an Endpoint to Support Accelerated Approval (May 2012). US DHHS FDA CDER; Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM305501.pdf</citation>
  </reference>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>September 2, 2014</study_first_submitted>
  <study_first_submitted_qc>September 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 12, 2014</study_first_posted>
  <last_update_submitted>October 25, 2017</last_update_submitted>
  <last_update_submitted_qc>October 25, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 26, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Toronto</investigator_affiliation>
    <investigator_full_name>Murray Krahn</investigator_full_name>
    <investigator_title>MD, MSc, FRCPC</investigator_title>
  </responsible_party>
  <keyword>Breast cancers</keyword>
  <keyword>Neoadjuvant chemotherapy</keyword>
  <keyword>RNA Disruption Assay™ (RDA) score</keyword>
  <keyword>Pathological Complete Response (pCR)</keyword>
  <keyword>Fine Needle Aspiration Biopsy</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/NCT02239315
org study id: 495462
nct id: NCT02239315
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this study is to find out if the pathological complete response (pCR) to
      chemotherapy given before surgery (neoadjuvant chemotherapy) could be predicted by the
      evaluation of the RNA (ribonucleic acids) disruption pattern (RNA Disruption Assay or RDA
      score) obtained from a biopsy of the tumor 7 - 14 days after the first, second and third
      cycles of chemotherapy treatment. If we can determine the optimal time during neoadjuvant
      chemotherapy to measure the RDA score for the prediction of pCR, we can optimize breast
      cancer management.
When administering neoadjuvant chemotherapy, the current practice of monitoring response to
      treatment is by measuring the size of the breast tumor after each cycle of chemotherapy. The
      drawback to this method is, it will take several weeks before we can actually measure a
      significant change in size; and the initial response to chemotherapy is often evident as a
      softening of the tumor without an apparent decrease of the tumor size. Finding a reliable way
      to identify early response to chemotherapy would be helpful to enable matching of
      chemotherapy to an individual's need.

      In a previous trial of breast cancer treated with neoadjuvant chemotherapy, researchers have
      identified that the pCR to a full treatment of chemotherapy could be predicted by the change
      in RNA pattern obtained from a biopsy of the tumor half way through the chemotherapy course.
      [Parissenti et al. 2010] The purpose of this study is to determine if we can predict the pCR
      to neoadjuvant chemotherapy by examining the pattern of RNA disruption (RNA Disruption Assay
      or RDA score) from breast biopsy tissue obtained 7 to 14 days after the first, second and
      third cycle of chemotherapy. If we can determine the optimal time during neoadjuvant
      chemotherapy to measure the RDA score for the prediction of pCR, we can optimize breast
      cancer management. For example, if RDA score can identify non-responders earlier, we can
      switch to other chemotherapy agents and reduce the exposure to the unnecessary side-effects
      of ineffective treatment.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: The association between RDA score and pathological complete response (pCR)
time frame: An expected average of 6 months
description: The association between tumor RDA score measured 7-14 days after the first, second and third cycles of chemotherapy and the pCR to neoadjuvant chemotherapy will be evaluated. pCR is defined as no evidence of invasive carcinoma in the breast and lymph nodes (ypT0/Tis ypN0/N0itc) on histology at the time of surgery (lumpectomy or mastectomy).
measure: The prognostic ability of RDA score
time frame: An expected average of 6 months
description: The capacity of RDA score to predict pCR to neoadjuvant chemotherapy will be assessed by exploring for a cut point on the RDA score to differentiate subjects with a high likelihood of achieving pCR versus those who are less likely to achieve pCR.
measure: The association between RDA score and clinical response (cR)
time frame: An expected average of 6 months
description: The association between tumor RDA score measured 7-14 days after the first, second and third cycles of chemotherapy and clinical response to neoadjuvant chemotherapy treatment will be evaluated.
measure: Patients' perception of fine needle aspiration biopsy (FNAB) and of breast cancer care
time frame: An expected average of 12 months
description: We shall seek to understand the experiences of patients with the FNAB procedure and with the cancer care they received while participating in the study by conducting qualitative interviews of study subjects.
measure: The cost-effectiveness of using RDA score
time frame: An expected average of 6 months
description: The cost-effectiveness of using RDA score to guide neoadjuvant chemotherapy will be evaluated by measuring the cost-effectiveness of monitoring pCR to neoadjuvant chemotherapy through the RDA score and in modifying the neoadjuvant chemotherapy regimen for non-pCR patients accordingly.
measure: The association between RDA score and Disease-Free Survival (DFS)
time frame: An expected average of 5 years
description: The association between tumor RDA score measured 7-14 days after the first, second and third cycles of chemotherapy and DFS will be evaluated. DFS will be measured as the time from patient's enrollment to the event of cancer metastasis or recurrence, or death, whatever comes first.
arm group label: Tumor RNA Disruption Assay™ (RDA)
arm group type: Experimental
description: Tumor RNA Disruption Assay™ (RDA) to generate RDA score from fine needle aspiration biopsy samples of breast cancer obtained 7-14 days after the first, second and third cycles of neoadjuvant chemotherapy; and, if there is a change of chemotherapy regimen, after the first cycle of the new chemotherapy.
intervention type: Other
intervention name: Tumor RNA Disruption Assay™ (RDA)
description: Tumor RNA Disruption Assay™ (RDA) to generate RDA score from fine needle aspiration biopsy samples of breast cancer obtained 7-14 days after the first, second and third cycles of neoadjuvant chemotherapy; and, if there is a change of chemotherapy regimen, after the first cycle of the new chemotherapy.
arm group label: Tumor RNA Disruption Assay™ (RDA)
other name: Biomarker
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Murray Krahn, MD,MSc,FRCPC
role: Principal Investigator
affiliation: Director of THETA Collaborative, the F. Norman Hughes Chair in Pharmacoeconomics and Social and Administrative Pharmacy Division Head in the Faculty of Pharmacy, Professor at the University of Toronto
facility: 
facility: 
facility: 
facility: 
country: Canada
citation: Parissenti AM, Chapman JA, Kahn HJ, Guo B, Han L, O'Brien P, Clemons MP, Jong R, Dent R, Fitzgerald B, Pritchard KI, Shepherd LE, Trudeau ME. Association of low tumor RNA integrity with response to chemotherapy in breast cancer patients. Breast Cancer Res Treat. 2010 Jan;119(2):347-56. doi: 10.1007/s10549-009-0531-x.
PMID: 19771508
citation: Schroeder A, Mueller O, Stocker S, Salowsky R, Leiber M, Gassmann M, Lightfoot S, Menzel W, Granzow M, Ragg T. The RIN: an RNA integrity number for assigning integrity values to RNA measurements. BMC Mol Biol. 2006 Jan 31;7:3. doi: 10.1186/1471-2199-7-3.
PMID: 16448564
citation: Guidance for Industry- Pathologic Complete Response in Neoadjuvant Treatment of High-Risk Early-Stage Breast Cancer: Use as an Endpoint to Support Accelerated Approval (May 2012). US DHHS FDA CDER; Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM305501.pdf
responsible party type: Principal Investigator
investigator affiliation: University of Toronto
investigator full name: Murray Krahn
investigator title: MD, MSc, FRCPC
mesh term: Breast Neoplasms