<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/NCT03238144</url>
  </required_header>
  <id_info>
    <org_study_id>204546</org_study_id>
    <nct_id>NCT03238144</nct_id>
  </id_info>
  <brief_title>Tissue Stresses of Cancer (Force Horizon 2020)</brief_title>
  <official_title>Tissue Stresses of Cancer: A Phase I/II,Multi-centre, Feasibility Study to Image the Tissue Stiffness/Stresses to Predict Outcome in Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Guy's and St Thomas' NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>King's College London</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Guy's and St Thomas' NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This project is investigating a novel MRI method called Magnetic Resonance Force (MRF). MRF&#xD;
      has been developed to accurately estimate tumour stiffness in the breast by measuring the&#xD;
      interstitial fluid pressure (IFP).&#xD;
&#xD;
      50 healthy volunteers will be recruited to extend the hardware and establish MRF imaging&#xD;
      acquisition protocols for pre and post-menopausal women. Once completed, we will test this&#xD;
      new imaging technique with the acquired imaging protocols on 100 patients undergoing surgery&#xD;
      as first line of their treatment for their breast cancer to establish a potential biomarker&#xD;
      signature predictive of lymph node involvement and metastatic potential. Simultaneously, 50&#xD;
      patients undergoing chemotherapy as first line of their treatment for their breast cancers&#xD;
      will be recruited to develop a biomarker signature that could predict response or resistance&#xD;
      to neoadjuvant chemotherapy as determined by conventional imaging and histopathology.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Magnetic Resonance Force (MRF) is based on Magnetic Resonance Elastography which uses&#xD;
      mechanical waves to quantitatively assess the viscoelastic properties of tumours and the&#xD;
      shift in interstitial fluid pressure (or stiffness) of tissues.&#xD;
&#xD;
      It generates 3D images of applied deformation via low frequency acoustic waves within the&#xD;
      tissue and provides a snapshot of the apparent stiffening of the tumour border zone. Growth&#xD;
      induced stretch of the tumour not only increases stiffness but also alters the apparent&#xD;
      change in stiffness due to additional loading. Magnetic Resonance Force (MRF) provides&#xD;
      measures of MRE and macro-deformation at multiple load states therefore enabling estimation&#xD;
      of tissue properties as well as the stress load relation. Since the stress load relation is&#xD;
      related to tumour swelling and modifications, it can be directly linked to the tumour&#xD;
      pre-strain and provides an indicator of the underlying interstitial tumour pressure. Using&#xD;
      biomechanical models it is possible to directly translate the stress load relation into an&#xD;
      estimate of IFP. The same approach also allows quantifying the active pull by cell traction&#xD;
      forces (CTFs) coming from the tumour and exerted onto its surroundings. While that force is&#xD;
      directed inwards, the force generated by the elevated interstitial fluid pressure (IFP) is&#xD;
      directed outwards allowing separation of both effects from each other. These forces represent&#xD;
      one of the biomarkers which we will quantify within the this project using MRF.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>November 2016</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">January 2019</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Evidence of reduction in interstitial fluid pressure confirmed by MRF</measure>
    <time_frame>up to 18 months</time_frame>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Breast Cancer Female</condition>
  <arm_group>
    <arm_group_label>MRF +/-contrast enhanced MRI</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>MRF with or without contrast enhanced MRI</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>MRF scan</intervention_name>
    <description>MRF with or without dynamic contrast-enhanced MRI scans.</description>
    <arm_group_label>MRF +/-contrast enhanced MRI</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria for healthy Volunteers:&#xD;
&#xD;
          -  Healthy female pre- and post-menopausal volunteers ≥ 40 years of age&#xD;
&#xD;
          -  Pre-menopausal patients between the age of 40-55 years of age will have two scans:&#xD;
&#xD;
               1. Between day 7- 15 of their menstrual cycle and&#xD;
&#xD;
               2. Between day 21-28 of their menstrual cycle&#xD;
&#xD;
          -  Postmenopausal patients of 55 years and above will have one scan only.&#xD;
&#xD;
          -  No prior history of breast cancer&#xD;
&#xD;
          -  Written informed consent to participate in this study&#xD;
&#xD;
        Inclusion Criteria for patients undergoing primary surgery:&#xD;
&#xD;
          -  Females ≥ 18 years of age with a diagnosis of invasive breast cancer with tumour size&#xD;
             of at least 5mm as determined by USS&#xD;
&#xD;
          -  Scheduled to undergo breast conserving surgery or mastectomy +/- sentinel lymph node&#xD;
             biopsy or axillary lymph node dissection&#xD;
&#xD;
          -  Written informed consent to participate in this study.&#xD;
&#xD;
        Inclusion Criteria for patients undergoing neoadjuvant chemotherapy:&#xD;
&#xD;
          -  Females ≥ 18 years of age with a diagnosis of invasive breast cancer&#xD;
&#xD;
          -  Scheduled to undergo neoadjuvant systemic chemotherapy&#xD;
&#xD;
          -  Written informed consent to participate in this study.&#xD;
&#xD;
        Exclusion Criteria for healthy volunteers:&#xD;
&#xD;
        Contraindications for MRI such as:&#xD;
&#xD;
          -  cardiac pacemaker&#xD;
&#xD;
          -  metallic implants&#xD;
&#xD;
          -  major claustrophobia&#xD;
&#xD;
          -  pregnancy or breastfeeding&#xD;
&#xD;
          -  Inability to provide written informed consent&#xD;
&#xD;
        Exclusion Criteria for patient undergoing primary surgery and neoadjuvant chemotherapy:&#xD;
&#xD;
          -  Contraindications for MRI such as:&#xD;
&#xD;
          -  cardiac pacemaker&#xD;
&#xD;
          -  metallic implants&#xD;
&#xD;
          -  major claustrophobia&#xD;
&#xD;
          -  prior breast cancer treatment&#xD;
&#xD;
          -  pregnancy or breastfeeding&#xD;
&#xD;
          -  known allergy against the contrast agent (gadolinium chelate) and renal failure&#xD;
&#xD;
          -  Inability to provide written informed consent&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Arnie Purushotham</last_name>
    <phone>0207 188 188</phone>
    <phone_ext>3027</phone_ext>
    <email>ea-purushotham@kcl.ac.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Sweta Sethi</last_name>
    <phone>02017 188 188</phone>
    <phone_ext>80743</phone_ext>
    <email>sweta.sethi@gstt.nhs.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Guy's and St.Thomas' NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <zip>SE1 9RT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sweta Sethi</last_name>
      <phone>0207 188 188</phone>
      <phone_ext>80743</phone_ext>
      <email>sweta.sethi@gstt.nhs.uk</email>
    </contact>
    <investigator>
      <last_name>Ralph Sinkus</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Keshthra Satchithananda</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Sarah Willson</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Anna Rigg</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Tony Ng</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>November 24, 2016</study_first_submitted>
  <study_first_submitted_qc>July 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 3, 2017</study_first_posted>
  <last_update_submitted>July 31, 2017</last_update_submitted>
  <last_update_submitted_qc>July 31, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 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>Undecided</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/NCT03238144
org study id: 204546
nct id: NCT03238144
lead sponsor: 
collaborator: 
has dmc: No
This project is investigating a novel MRI method called Magnetic Resonance Force (MRF). MRF
      has been developed to accurately estimate tumour stiffness in the breast by measuring the
      interstitial fluid pressure (IFP).

      50 healthy volunteers will be recruited to extend the hardware and establish MRF imaging
      acquisition protocols for pre and post-menopausal women. Once completed, we will test this
      new imaging technique with the acquired imaging protocols on 100 patients undergoing surgery
      as first line of their treatment for their breast cancer to establish a potential biomarker
      signature predictive of lymph node involvement and metastatic potential. Simultaneously, 50
      patients undergoing chemotherapy as first line of their treatment for their breast cancers
      will be recruited to develop a biomarker signature that could predict response or resistance
      to neoadjuvant chemotherapy as determined by conventional imaging and histopathology.
Magnetic Resonance Force (MRF) is based on Magnetic Resonance Elastography which uses
      mechanical waves to quantitatively assess the viscoelastic properties of tumours and the
      shift in interstitial fluid pressure (or stiffness) of tissues.

      It generates 3D images of applied deformation via low frequency acoustic waves within the
      tissue and provides a snapshot of the apparent stiffening of the tumour border zone. Growth
      induced stretch of the tumour not only increases stiffness but also alters the apparent
      change in stiffness due to additional loading. Magnetic Resonance Force (MRF) provides
      measures of MRE and macro-deformation at multiple load states therefore enabling estimation
      of tissue properties as well as the stress load relation. Since the stress load relation is
      related to tumour swelling and modifications, it can be directly linked to the tumour
      pre-strain and provides an indicator of the underlying interstitial tumour pressure. Using
      biomechanical models it is possible to directly translate the stress load relation into an
      estimate of IFP. The same approach also allows quantifying the active pull by cell traction
      forces (CTFs) coming from the tumour and exerted onto its surroundings. While that force is
      directed inwards, the force generated by the elevated interstitial fluid pressure (IFP) is
      directed outwards allowing separation of both effects from each other. These forces represent
      one of the biomarkers which we will quantify within the this project using MRF.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Evidence of reduction in interstitial fluid pressure confirmed by MRF
time frame: up to 18 months
arm group label: MRF +/-contrast enhanced MRI
arm group type: Other
description: MRF with or without contrast enhanced MRI
intervention type: Other
intervention name: MRF scan
description: MRF with or without dynamic contrast-enhanced MRI scans.
arm group label: MRF +/-contrast enhanced MRI
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Arnie Purushotham
phone: 0207 188 188
phone ext: 3027
email: ea-purushotham@kcl.ac.uk
last name: Sweta Sethi
phone: 02017 188 188
phone ext: 80743
email: sweta.sethi@gstt.nhs.uk
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Breast Neoplasms
sharing ipd: Undecided