<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/NCT03302819</url>
  </required_header>
  <id_info>
    <org_study_id>CCR4702</org_study_id>
    <nct_id>NCT03302819</nct_id>
  </id_info>
  <brief_title>London Investigation Into diElectric Scanning of Lesions</brief_title>
  <acronym>LIESL</acronym>
  <official_title>Performance Evaluation of the MARIA (Multi Static Array Processing of Radiowave Image Acquisition) Radar Breast Imaging System in Patients With Breast Cancer and in Patients Assessed in the Symptomatic Breast Clinic.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Royal Marsden NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Micrima, Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Royal Marsden NHS Foundation Trust</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The MARIA breast imaging system is a novel CE-marked radio-frequency (RF) medical imaging&#xD;
      device. The system employs an electromagnetic imaging technique that exploits the dielectric&#xD;
      contrast between normal and cancerous tissues. The performance and imaging characteristics of&#xD;
      MARIA are not yet well demonstrated. The investigators aim to evaluate some aspects of this&#xD;
      potentially important new technology.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The early diagnosis of breast cancer is of paramount importance, with a 5-year survival rate&#xD;
      of 97% if the cancer is caught &quot;locally&quot;, deteriorating to 79% if it has progressed to the&#xD;
      &quot;axillary&quot; lymph nodes, and 23% if it has spread to the rest of the body, known as&#xD;
      &quot;metastasised.&quot;&#xD;
&#xD;
      Diagnosis is currently achieved through clinical examination, imaging with mammography (MMG)&#xD;
      and/or ultrasound (US) and needle biopsy. Mammography is dependent upon adequate breast&#xD;
      compression to allow greater contrast differentiation between tissue structures, this is not&#xD;
      only uncomfortable, but in younger women with 'dense' breast tissue the contrast difference&#xD;
      between normal tissue and tumour is minimal despite compression. Furthermore mammography uses&#xD;
      ionising radiation, which means that a risk/benefit calculation is weighted against repeated&#xD;
      or frequent use. Frequently it is necessary to use additional imaging such as ultrasound or&#xD;
      MRI for diagnostic support.&#xD;
&#xD;
      Breast tumours have an additional property that can distinguish them from normal and this is&#xD;
      defined by the dielectric value. This has two components - the dielectric constant, which&#xD;
      affects the velocity of propagation of radio waves and therefore their wavelength, and the&#xD;
      conductivity, which affects the rate of attenuation. Typically a tumour has a dielectric&#xD;
      constant of 45-50 and a conductivity of 2S/m, whereas breast fat is 5-15 and 0.2-1S/m&#xD;
      respectively but with considerable range. Normal glandular tissue is intermediate. These&#xD;
      differences in dielectric constant enable a consideration of the value of this data in breast&#xD;
      cancer diagnosis.&#xD;
&#xD;
      Several attempts to exploit this property for imaging have been made. The outcomes have been&#xD;
      similar in that the presence of a tumour is detectable, however limitations in depth for&#xD;
      detection and mode of the technology were identified.&#xD;
&#xD;
      Due to updated technology in the MARIA device, previous limitations from similar studies are&#xD;
      not reported to be a problem.&#xD;
&#xD;
      This study aims to determine the proportion of patients with breast cancer who are correctly&#xD;
      diagnosed by MARIA, and to stratify this by breast density and histological type. In addition&#xD;
      a pilot study will be performed to investigate the imaging characteristics and performance of&#xD;
      MARIA in the assessment of benign and malignant lesions in patients attending the symptomatic&#xD;
      breast clinic.&#xD;
&#xD;
      The MARIA scan will be in addition to any standard diagnostic procedures, including imaging,&#xD;
      that comprise the standard of care. The scan will require them to lie prone for less than 10&#xD;
      minutes with their breast pendant in an ergonomically-fitted bowl with a thin layer of a&#xD;
      coupling fluid (similar to hand moisture in consistency) applied to the surface of the&#xD;
      breast.&#xD;
&#xD;
      While there is no direct benefit nor detrimental effect from this study to the patients&#xD;
      participating, the study has large implications for many women.&#xD;
&#xD;
      This study will allow the investigators to test the feasibility of this highly innovating&#xD;
      approach to breast cancer, with minimal negative effects or possible complications. This&#xD;
      diagnostic modality could prove to be a major step forwards in cancer detection, initially as&#xD;
      a complementary source of information that can increase confidence in results obtained from&#xD;
      established technologies that are routinely deployed in the clinic.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">November 1, 2017</start_date>
  <completion_date type="Anticipated">December 1, 2018</completion_date>
  <primary_completion_date type="Anticipated">November 1, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of patients with breast cancer in whom breast cancer is correctly identified by MARIA</measure>
    <time_frame>1 week (after histopathology result)</time_frame>
    <description>Comparison to histopathology result</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Sensitivity and specificity of MARIA for a range of findings to include, simple cysts, fibroadenomata, and malignant lesions. As judged against the final diagnosis at discharge, which may be based on clinical findings, imaging and pathology data.</measure>
    <time_frame>Through study completion, an average of 1 year</time_frame>
    <description>Comparison with clinical, radiology and pathology findings</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Proportion of post-operative patients treated with neo-adjuvant chemotherapy or endocrine therapy, correctly identified by MARIA with complete response or residual disease, as compared to surgical histology.</measure>
    <time_frame>Through study completion, an average of 1 year</time_frame>
    <description>Comparison of response to surgical histology</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Compare the detection of breast cancer from MARIA with the detection from mammography by the sub-group of histology type.</measure>
    <time_frame>Through study completion, an average of 1 year</time_frame>
    <description>Comparison to Mammography and Pathology result</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the detection of breast cancer from MARIA with the detection from mammography by sub-group of mammographic density.</measure>
    <time_frame>Through study completion, an average of 1 year</time_frame>
    <description>Comparison to Mammography and Pathology result</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the detection of breast cancer from MARIA with the detection from mammography in the overall patient group.</measure>
    <time_frame>Through study completion, an average of 1 year</time_frame>
    <description>Comparison to Mammography and Pathology result</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of data repeatability (test re-test) of MARIA assessment results on patients with diagnostic follow-up imaging.</measure>
    <time_frame>After attendance for further imaging, at 1-2 weeks.</time_frame>
    <description>Comparison with prior MARIA scan when returning for further imaging</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Investigate the performance of MARIA in the estimation of residual tumour size compared to the final surgical histology results in the case of patients receiving neo-adjuvant chemotherapy or endocrine therapy.</measure>
    <time_frame>Through study completion, an average of 1 year</time_frame>
    <description>The correlation between the pathological features of the lesion and the imaging features as determined from MARIA including presence of features, shape and size.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient tolerance of MARIA (a non-compressing, non-ionising modality)</measure>
    <time_frame>Through study completion, an average of 1 year</time_frame>
    <description>Questionnaire measurement, Quantitative answers.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">994</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Breast cancer accuracy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with a known or suspected (and subsequently proven) breast cancer</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Imaging characteristics and performance</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients attending the symptomatic clinic</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tumour response in neoadjuvant treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients who are being treated with neoadjuvant chemotherapy or endocrine treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>MARIA scan</intervention_name>
    <description>The patient will have an additional MARIA scan along with conventional imaging, pathology and surgical procedures.</description>
    <arm_group_label>Breast cancer accuracy</arm_group_label>
    <arm_group_label>Imaging characteristics and performance</arm_group_label>
    <arm_group_label>Tumour response in neoadjuvant treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Attending a symptomatic breast care clinic OR Patients who have a diagnosed or&#xD;
             suspected breast cancer (P5/M5/U5/B5).&#xD;
&#xD;
          -  Female sex&#xD;
&#xD;
          -  18 years or older.&#xD;
&#xD;
          -  Able to provide informed consent.&#xD;
&#xD;
          -  Not in any identified, vulnerable group.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unable to mount MARIA™ patient bed using provided 2-step&#xD;
&#xD;
          -  Unable to lie in the prone position&#xD;
&#xD;
          -  Patients who have undergone biopsy less than 5 days before the MARIA™ scan&#xD;
&#xD;
          -  Patients with implanted electronics.&#xD;
&#xD;
          -  Patients with breast implants.&#xD;
&#xD;
          -  Patients with nipple piercings (unless they are removed prior to the MARIA™ scan)&#xD;
&#xD;
          -  Breast sizes smaller than 197ml or greater than 1L in volume&#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>Steven Allen</last_name>
    <role>Study Chair</role>
    <affiliation>Royal Marsden NHS Foundation Trust</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Richard Sidebottom</last_name>
    <role>Principal Investigator</role>
    <affiliation>Royal Marsden NHS Foundation Trust</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Richard Sidebottom</last_name>
    <phone>02073528171</phone>
    <phone_ext>1407</phone_ext>
    <email>richardsidebottom@nhs.net</email>
  </overall_contact>
  <reference>
    <citation>Preece AW, Craddock I, Shere M, Jones L, Winton HL. MARIA M4: clinical evaluation of a prototype ultrawideband radar scanner for breast cancer detection. J Med Imaging (Bellingham). 2016 Jul;3(3):033502. doi: 10.1117/1.JMI.3.3.033502. Epub 2016 Jul 20.</citation>
    <PMID>27446970</PMID>
  </reference>
  <reference>
    <citation>Saadatmand S, Bretveld R, Siesling S, Tilanus-Linthorst MM. Influence of tumour stage at breast cancer detection on survival in modern times: population based study in 173,797 patients. BMJ. 2015 Oct 6;351:h4901. doi: 10.1136/bmj.h4901.</citation>
    <PMID>26442924</PMID>
  </reference>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 21, 2017</study_first_submitted>
  <study_first_submitted_qc>October 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 5, 2017</study_first_posted>
  <last_update_submitted>October 4, 2017</last_update_submitted>
  <last_update_submitted_qc>October 4, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 5, 2017</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>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/NCT03302819
org study id: CCR4702
nct id: NCT03302819
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
The MARIA breast imaging system is a novel CE-marked radio-frequency (RF) medical imaging
      device. The system employs an electromagnetic imaging technique that exploits the dielectric
      contrast between normal and cancerous tissues. The performance and imaging characteristics of
      MARIA are not yet well demonstrated. The investigators aim to evaluate some aspects of this
      potentially important new technology.
The early diagnosis of breast cancer is of paramount importance, with a 5-year survival rate
      of 97% if the cancer is caught "locally", deteriorating to 79% if it has progressed to the
      "axillary" lymph nodes, and 23% if it has spread to the rest of the body, known as
      "metastasised."

      Diagnosis is currently achieved through clinical examination, imaging with mammography (MMG)
      and/or ultrasound (US) and needle biopsy. Mammography is dependent upon adequate breast
      compression to allow greater contrast differentiation between tissue structures, this is not
      only uncomfortable, but in younger women with 'dense' breast tissue the contrast difference
      between normal tissue and tumour is minimal despite compression. Furthermore mammography uses
      ionising radiation, which means that a risk/benefit calculation is weighted against repeated
      or frequent use. Frequently it is necessary to use additional imaging such as ultrasound or
      MRI for diagnostic support.

      Breast tumours have an additional property that can distinguish them from normal and this is
      defined by the dielectric value. This has two components - the dielectric constant, which
      affects the velocity of propagation of radio waves and therefore their wavelength, and the
      conductivity, which affects the rate of attenuation. Typically a tumour has a dielectric
      constant of 45-50 and a conductivity of 2S/m, whereas breast fat is 5-15 and 0.2-1S/m
      respectively but with considerable range. Normal glandular tissue is intermediate. These
      differences in dielectric constant enable a consideration of the value of this data in breast
      cancer diagnosis.

      Several attempts to exploit this property for imaging have been made. The outcomes have been
      similar in that the presence of a tumour is detectable, however limitations in depth for
      detection and mode of the technology were identified.

      Due to updated technology in the MARIA device, previous limitations from similar studies are
      not reported to be a problem.

      This study aims to determine the proportion of patients with breast cancer who are correctly
      diagnosed by MARIA, and to stratify this by breast density and histological type. In addition
      a pilot study will be performed to investigate the imaging characteristics and performance of
      MARIA in the assessment of benign and malignant lesions in patients attending the symptomatic
      breast clinic.

      The MARIA scan will be in addition to any standard diagnostic procedures, including imaging,
      that comprise the standard of care. The scan will require them to lie prone for less than 10
      minutes with their breast pendant in an ergonomically-fitted bowl with a thin layer of a
      coupling fluid (similar to hand moisture in consistency) applied to the surface of the
      breast.

      While there is no direct benefit nor detrimental effect from this study to the patients
      participating, the study has large implications for many women.

      This study will allow the investigators to test the feasibility of this highly innovating
      approach to breast cancer, with minimal negative effects or possible complications. This
      diagnostic modality could prove to be a major step forwards in cancer detection, initially as
      a complementary source of information that can increase confidence in results obtained from
      established technologies that are routinely deployed in the clinic.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Proportion of patients with breast cancer in whom breast cancer is correctly identified by MARIA
time frame: 1 week (after histopathology result)
description: Comparison to histopathology result
measure: Sensitivity and specificity of MARIA for a range of findings to include, simple cysts, fibroadenomata, and malignant lesions. As judged against the final diagnosis at discharge, which may be based on clinical findings, imaging and pathology data.
time frame: Through study completion, an average of 1 year
description: Comparison with clinical, radiology and pathology findings
measure: Proportion of post-operative patients treated with neo-adjuvant chemotherapy or endocrine therapy, correctly identified by MARIA with complete response or residual disease, as compared to surgical histology.
time frame: Through study completion, an average of 1 year
description: Comparison of response to surgical histology
measure: Compare the detection of breast cancer from MARIA with the detection from mammography by the sub-group of histology type.
time frame: Through study completion, an average of 1 year
description: Comparison to Mammography and Pathology result
measure: Compare the detection of breast cancer from MARIA with the detection from mammography by sub-group of mammographic density.
time frame: Through study completion, an average of 1 year
description: Comparison to Mammography and Pathology result
measure: Compare the detection of breast cancer from MARIA with the detection from mammography in the overall patient group.
time frame: Through study completion, an average of 1 year
description: Comparison to Mammography and Pathology result
measure: Assessment of data repeatability (test re-test) of MARIA assessment results on patients with diagnostic follow-up imaging.
time frame: After attendance for further imaging, at 1-2 weeks.
description: Comparison with prior MARIA scan when returning for further imaging
measure: Investigate the performance of MARIA in the estimation of residual tumour size compared to the final surgical histology results in the case of patients receiving neo-adjuvant chemotherapy or endocrine therapy.
time frame: Through study completion, an average of 1 year
description: The correlation between the pathological features of the lesion and the imaging features as determined from MARIA including presence of features, shape and size.
measure: Patient tolerance of MARIA (a non-compressing, non-ionising modality)
time frame: Through study completion, an average of 1 year
description: Questionnaire measurement, Quantitative answers.
arm group label: Breast cancer accuracy
arm group type: Experimental
description: Patients with a known or suspected (and subsequently proven) breast cancer
arm group label: Imaging characteristics and performance
arm group type: Experimental
description: Patients attending the symptomatic clinic
arm group label: Tumour response in neoadjuvant treatment
arm group type: Experimental
description: Patients who are being treated with neoadjuvant chemotherapy or endocrine treatment
intervention type: Diagnostic Test
intervention name: MARIA scan
description: The patient will have an additional MARIA scan along with conventional imaging, pathology and surgical procedures.
arm group label: Breast cancer accuracy
arm group label: Imaging characteristics and performance
arm group label: Tumour response in neoadjuvant treatment
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Steven Allen
role: Study Chair
affiliation: Royal Marsden NHS Foundation Trust
last name: Richard Sidebottom
role: Principal Investigator
affiliation: Royal Marsden NHS Foundation Trust
last name: Richard Sidebottom
phone: 02073528171
phone ext: 1407
email: richardsidebottom@nhs.net
citation: Preece AW, Craddock I, Shere M, Jones L, Winton HL. MARIA M4: clinical evaluation of a prototype ultrawideband radar scanner for breast cancer detection. J Med Imaging (Bellingham). 2016 Jul;3(3):033502. doi: 10.1117/1.JMI.3.3.033502. Epub 2016 Jul 20.
PMID: 27446970
citation: Saadatmand S, Bretveld R, Siesling S, Tilanus-Linthorst MM. Influence of tumour stage at breast cancer detection on survival in modern times: population based study in 173,797 patients. BMJ. 2015 Oct 6;351:h4901. doi: 10.1136/bmj.h4901.
PMID: 26442924
responsible party type: Sponsor
mesh term: Breast Neoplasms
sharing ipd: No