<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/NCT03818100</url>
  </required_header>
  <id_info>
    <org_study_id>Neo-RT</org_study_id>
    <nct_id>NCT03818100</nct_id>
  </id_info>
  <brief_title>Neo-RT: A Study Investigating Whether Changing the Sequence of Treatments (Starting Radiotherapy Followed by Hormone Therapy Before Surgery) is Feasible</brief_title>
  <acronym>Neo-RT</acronym>
  <official_title>Neo-RT: Pre-operative Breast Intensity Modulated Radiotherapy in Patients Receiving Neo-adjuvant Hormonal Treatment for Breast Cancer - a Feasibility Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CCTU- Cancer Theme</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Breast Cancer Now</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>CRUK Cambridge Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Cambridge University Hospitals NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Four in 10 women diagnosed with breast cancer undergo mastectomy with or without breast&#xD;
      reconstruction and less than half are satisfied with how they look unclothed. Breast&#xD;
      conservation (removing the area with the lump only) can offer less extensive surgery and&#xD;
      improved breast appearance, which can therefore increase well-being.&#xD;
&#xD;
      Intensity-modulated radiotherapy (IMRT) closely shapes the radiation beam to the cancer and&#xD;
      is currently given after breast surgery. A new combination of IMRT followed by hormone&#xD;
      treatment given before surgery, may increase the possibility of breast conservation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 26, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">April 30, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>The proportion of patients successfully completing neo-adjuvant IMRT and endocrine treatment followed by beast surgery, as per study protocol.</measure>
    <time_frame>6 months</time_frame>
    <description>Successful completion of IMRT is defined as:&#xD;
Treatment received was either 48 Gy/15# or 40 Gy/15# with sequential boost&#xD;
Treatment received was 'other', but the reason for different schedule was not due to toxicity related from the radiotherapy&#xD;
Radiotherapy treatment was not delayed by 5 days or more&#xD;
Radiotherapy treatment was delayed by 5 days or more, but the reason was not due to toxicity related from the radiotherapy&#xD;
Successful completion of endocrine treatment is defined as:&#xD;
Patient received at least 80% of endocrine treatment received&#xD;
Patient did not receive 80% of endocrine treatment, but the reason was not due to toxicity or toxicity related from radiotherapy or endocrine&#xD;
Successful surgery is defined as:&#xD;
Planned date of surgery is not delayed&#xD;
Planned date of surgery is delayed, but the reason was not due to toxicity or toxicity related to radiotherapy or endocrine treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Acute radiotherapy toxicity following IMRT, assessed by CTCAE v4.03</measure>
    <time_frame>3 weeks</time_frame>
    <description>Acute radiotherapy toxicity following IMRT, assessed by CTCAE v4.03</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mastectomy rate</measure>
    <time_frame>6 months</time_frame>
    <description>Analysis will be descriptive, and in accordance to the statistical analysis plan.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peri/post operative complications</measure>
    <time_frame>9 months</time_frame>
    <description>Including:&#xD;
Length of stay&#xD;
Unplanned return to theatre (and reason)&#xD;
Use of antibiotics for wound related issues&#xD;
Number of clinic attendances for wound related problems</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of residual tumour and response to treatment</measure>
    <time_frame>6 months</time_frame>
    <description>There will be a central review (2 readers) of all primary surgery histopathology reports for the secondary endpoint of pathological complete response (pCR). The histopathology slides from the surgical resection will be requested for central assessment of residual disease for all cases where there has not been a pCR. The variables that will be recorded include residual invasive tumour size in two dimensions, residual invasive tumour cellularity, number of lymph node metastases and size of the largest metastasis. A representative tumour tissue block will be selected and requested from the laboratory. Sections from the block will be taken for staining with ER and Ki67 to allow calculation of the histological assessment of residual tumour burden, and cores taken as per the protocol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Late normal tissue toxicity, as assessed by: 1) clinicians</measure>
    <time_frame>Annually for 5 years</time_frame>
    <description>Clinician - post-radiotherapy questionnaire (with permission from IMPORT Trial Management Group and Dr Penny Hopwood)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Late normal tissue toxicity, as assessed by: 2) Patient Reported Outcome Measurements (PROMs)</measure>
    <time_frame>Annually for 5 years</time_frame>
    <description>Patient Reported Outcome Measure - Validated Breast-Q questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Late normal tissue toxicity, as assessed by: 2) Patient Reported Outcome Measurements (PROMs)</measure>
    <time_frame>Annually for 5 years</time_frame>
    <description>Patient Reported Outcome Measure - EORTC IL1 Modified BRECON23 PROM questionnaire.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Exploratory research will be carried out to identify possible molecular and radiological biomarkers of response</measure>
    <time_frame>6 months post last patient recruited</time_frame>
    <description>Exploratory investigation of potential biomarkers include:&#xD;
ctDNA,&#xD;
PBMCs,&#xD;
Tumour molecular profiles,&#xD;
Immunohistochemical/immunofluorescence markers of:&#xD;
Immune response (TILs) Tumour proliferation (Ki67, Geminin) DNA damage response and cell cycle checkpoint activation (including 53BP1, RAD51, ATM1, BRCA1, p53, p21 and p-chk-1) Tumour microenvironment (hypoxia)&#xD;
- Multiplexed single cell proteomics of both cellular suspensions (including whole blood) and intact tissues, to investigate the immune response and other novel markers&#xD;
Since the identification of new biomarkers correlating with disease activity and the efficacy or safety of treatment is rapidly evolving, the definitive list of biomarkers remains to be determined. However they will be detailed in an appropriate analysis plan prior to undertaking any sample analysis.</description>
  </other_outcome>
  <enrollment type="Anticipated">43</enrollment>
  <condition>Breast Cancer</condition>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Intensity modulated radiotherapy (IMRT)</intervention_name>
    <description>Simultaneous integrated boost technique using IMRT: 48 Gray (Gy) and 40 Gy will treat tumour and breast tissue respectively, in 15 fractions over 3 weeks.</description>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Endocrine therapy</intervention_name>
    <description>Endocrine therapy will commence following completion of radiotherapy, and will continue for 20 weeks.</description>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Breast conserving surgery</intervention_name>
    <description>Surgery carried out using local protocol following completion of endocrine therapy.</description>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Tumour tissue samples, blood samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Women with invasive breast cancer for planned treatment with neo-adjuvant endocrine&#xD;
        therapy, where radiotherapy may make breast conserving surgery easier.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent to participate&#xD;
&#xD;
          -  Female&#xD;
&#xD;
          -  Aged 18 years and older&#xD;
&#xD;
          -  ECOG performance status 0-2&#xD;
&#xD;
          -  Histology confirmed invasive breast cancer&#xD;
&#xD;
          -  ER positive (Allred score 6-8)&#xD;
&#xD;
          -  HER2 negative&#xD;
&#xD;
          -  Palpable size ≥20mm&#xD;
&#xD;
          -  Grade I-II (or grade III if considered not suitable for neo-adjuvant chemotherapy)&#xD;
&#xD;
          -  Considered that radiotherapy will make breast conserving surgery easier&#xD;
&#xD;
          -  No evidence of non-breast malignancy if treated with curative intent unless the&#xD;
             patient has been disease free ≥5 years&#xD;
&#xD;
          -  Unifocal or multifocal disease, i.e. tumour in the same quadrant and breast conserving&#xD;
             surgery still feasible&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contraindications to breast radiotherapy or neo-adjuvant endocrine therapy&#xD;
&#xD;
          -  Bilateral breast cancer&#xD;
&#xD;
          -  Metastatic cancer&#xD;
&#xD;
          -  Multicentric disease&#xD;
&#xD;
          -  Concomitant medical/psychiatric problems preventing completion of study treatment or&#xD;
             follow-up&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Breast feeding&#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>Charlotte E Coles, MB ChB, MRCP, FRCR, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Cambridge</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Victoria Ingleson, BSc</last_name>
    <phone>01223 349702</phone>
    <email>victoria.ingleson@addenbrookes.nhs.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Anne-Laure Vallier</last_name>
    <phone>01223 348086</phone>
    <email>anne-laure.vallier@addenbrookes.nhs.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Cambridge University Hospitals NHS Foundation Trust</name>
      <address>
        <city>Cambridge</city>
        <state>Cambridgeshire</state>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Meena Murthy, BSc</last_name>
      <phone>01223 349702</phone>
      <email>meena.murthy@addenbrookes.nhs.uk</email>
    </contact>
    <contact_backup>
      <last_name>Anne-Laure Vallier</last_name>
      <phone>01223 348086</phone>
      <email>anne-laure.vallier@addenbrookes.nhs.uk</email>
    </contact_backup>
    <investigator>
      <last_name>Charlotte Coles</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>July 24, 2018</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>July 26, 2021</last_update_submitted>
  <last_update_submitted_qc>July 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Cambridge University Hospitals NHS Foundation Trust</investigator_affiliation>
    <investigator_full_name>CCTU- Cancer Theme</investigator_full_name>
    <investigator_title>Dr Charlotte Coles</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>
  <!-- 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/NCT03818100
org study id: Neo-RT
nct id: NCT03818100
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Four in 10 women diagnosed with breast cancer undergo mastectomy with or without breast
      reconstruction and less than half are satisfied with how they look unclothed. Breast
      conservation (removing the area with the lump only) can offer less extensive surgery and
      improved breast appearance, which can therefore increase well-being.

      Intensity-modulated radiotherapy (IMRT) closely shapes the radiation beam to the cancer and
      is currently given after breast surgery. A new combination of IMRT followed by hormone
      treatment given before surgery, may increase the possibility of breast conservation.
observational model: Cohort
time perspective: Prospective
measure: The proportion of patients successfully completing neo-adjuvant IMRT and endocrine treatment followed by beast surgery, as per study protocol.
time frame: 6 months
description: Successful completion of IMRT is defined as:
Treatment received was either 48 Gy/15# or 40 Gy/15# with sequential boost
Treatment received was 'other', but the reason for different schedule was not due to toxicity related from the radiotherapy
Radiotherapy treatment was not delayed by 5 days or more
Radiotherapy treatment was delayed by 5 days or more, but the reason was not due to toxicity related from the radiotherapy
Successful completion of endocrine treatment is defined as:
Patient received at least 80% of endocrine treatment received
Patient did not receive 80% of endocrine treatment, but the reason was not due to toxicity or toxicity related from radiotherapy or endocrine
Successful surgery is defined as:
Planned date of surgery is not delayed
Planned date of surgery is delayed, but the reason was not due to toxicity or toxicity related to radiotherapy or endocrine treatment.
measure: Acute radiotherapy toxicity following IMRT, assessed by CTCAE v4.03
time frame: 3 weeks
description: Acute radiotherapy toxicity following IMRT, assessed by CTCAE v4.03
measure: Mastectomy rate
time frame: 6 months
description: Analysis will be descriptive, and in accordance to the statistical analysis plan.
measure: Peri/post operative complications
time frame: 9 months
description: Including:
Length of stay
Unplanned return to theatre (and reason)
Use of antibiotics for wound related issues
Number of clinic attendances for wound related problems
measure: Volume of residual tumour and response to treatment
time frame: 6 months
description: There will be a central review (2 readers) of all primary surgery histopathology reports for the secondary endpoint of pathological complete response (pCR). The histopathology slides from the surgical resection will be requested for central assessment of residual disease for all cases where there has not been a pCR. The variables that will be recorded include residual invasive tumour size in two dimensions, residual invasive tumour cellularity, number of lymph node metastases and size of the largest metastasis. A representative tumour tissue block will be selected and requested from the laboratory. Sections from the block will be taken for staining with ER and Ki67 to allow calculation of the histological assessment of residual tumour burden, and cores taken as per the protocol.
measure: Late normal tissue toxicity, as assessed by: 1) clinicians
time frame: Annually for 5 years
description: Clinician - post-radiotherapy questionnaire (with permission from IMPORT Trial Management Group and Dr Penny Hopwood)
measure: Late normal tissue toxicity, as assessed by: 2) Patient Reported Outcome Measurements (PROMs)
time frame: Annually for 5 years
description: Patient Reported Outcome Measure - Validated Breast-Q questionnaire
measure: Late normal tissue toxicity, as assessed by: 2) Patient Reported Outcome Measurements (PROMs)
time frame: Annually for 5 years
description: Patient Reported Outcome Measure - EORTC IL1 Modified BRECON23 PROM questionnaire.
measure: Exploratory research will be carried out to identify possible molecular and radiological biomarkers of response
time frame: 6 months post last patient recruited
description: Exploratory investigation of potential biomarkers include:
ctDNA,
PBMCs,
Tumour molecular profiles,
Immunohistochemical/immunofluorescence markers of:
Immune response (TILs) Tumour proliferation (Ki67, Geminin) DNA damage response and cell cycle checkpoint activation (including 53BP1, RAD51, ATM1, BRCA1, p53, p21 and p-chk-1) Tumour microenvironment (hypoxia)
- Multiplexed single cell proteomics of both cellular suspensions (including whole blood) and intact tissues, to investigate the immune response and other novel markers
Since the identification of new biomarkers correlating with disease activity and the efficacy or safety of treatment is rapidly evolving, the definitive list of biomarkers remains to be determined. However they will be detailed in an appropriate analysis plan prior to undertaking any sample analysis.
intervention type: Radiation
intervention name: Intensity modulated radiotherapy (IMRT)
description: Simultaneous integrated boost technique using IMRT: 48 Gray (Gy) and 40 Gy will treat tumour and breast tissue respectively, in 15 fractions over 3 weeks.
intervention type: Drug
intervention name: Endocrine therapy
description: Endocrine therapy will commence following completion of radiotherapy, and will continue for 20 weeks.
intervention type: Procedure
intervention name: Breast conserving surgery
description: Surgery carried out using local protocol following completion of endocrine therapy.
Tumour tissue samples, blood samples
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Charlotte E Coles, MB ChB, MRCP, FRCR, PhD
role: Principal Investigator
affiliation: University of Cambridge
last name: Victoria Ingleson, BSc
phone: 01223 349702
email: victoria.ingleson@addenbrookes.nhs.uk
last name: Anne-Laure Vallier
phone: 01223 348086
email: anne-laure.vallier@addenbrookes.nhs.uk
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United Kingdom
responsible party type: Sponsor-Investigator
investigator affiliation: Cambridge University Hospitals NHS Foundation Trust
investigator full name: CCTU- Cancer Theme
investigator title: Dr Charlotte Coles
mesh term: Breast Neoplasms