<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/NCT04493723</url>
  </required_header>
  <id_info>
    <org_study_id>CFTSp157</org_study_id>
    <secondary_id>18/NW/0515</secondary_id>
    <secondary_id>132792</secondary_id>
    <nct_id>NCT04493723</nct_id>
  </id_info>
  <brief_title>Serial Tumour Biopsies and Blood Biomarkers in Melanoma</brief_title>
  <official_title>Molecular Characterisation of Serial Tumour Samples and Their Correlation With Circulating Biomarkers and Other Biospecimens Taken During the Clinical Course of Patients Receiving Treatment for Malignant Melanoma.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Christie NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Manchester</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The Christie NHS Foundation Trust</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>
      Recent advances in understanding how cancer develops and spreads have led to effective new&#xD;
      treatments and improved outcomes for patients with melanoma. However, we know that these new&#xD;
      treatments do not work for all patients: some do not respond to them and some initially&#xD;
      respond but then develop resistance. The overall aim of this study will be to collect tumour&#xD;
      biopsies, biomarkers present in the blood, and other biological specimens which can be used&#xD;
      to try to understand why resistance to anti-cancer treatment occurs, and to develop&#xD;
      predictive biomarkers of this resistance in patients with locally advanced and metastatic&#xD;
      malignant melanoma.&#xD;
&#xD;
      The study will be open to NHS patients aged 16 and over, who have been diagnosed with&#xD;
      advanced melanoma, and who will be receiving treatment for their disease as part of their&#xD;
      routine care. Patients will be asked to provide samples from tumour biopsies before, during&#xD;
      and after treatment. We will also ask for blood samples to look at biomarkers in the blood&#xD;
      and see how these correspond with tumour samples, which will further help us to understand&#xD;
      treatment response. Biomarkers are substances in the body that can be measured and help&#xD;
      indicate how a disease is developing. It is hoped that soon we will be able to monitor cancer&#xD;
      by analysing a patient's blood samples, thus reducing the need for biopsies. As blood tests&#xD;
      could be taken more frequently, signs that patients are becoming resistant to treatments&#xD;
      could be picked up sooner.&#xD;
&#xD;
      As well as monitoring biomarkers, we would also like to understand what happens to the&#xD;
      healthy cells surrounding the tumour during treatment. This will improve our understanding of&#xD;
      how cells adapt and respond to treatments, and may eventually lead to the discovery of new&#xD;
      biomarkers to help predict which patients will develop resistance to certain treatments.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be a prospective study recruiting patients who have been diagnosed wth advanced&#xD;
      melanoma.&#xD;
&#xD;
      Participants will be asked to give informed consent before any samples are collected.&#xD;
&#xD;
      Participants will be asked to donate tissue and other biospecimens (see list below) that are&#xD;
      surplus to clinical requirements if a participant is undergoing any of the following as part&#xD;
      of their routine care:&#xD;
&#xD;
        -  lymph node dissection&#xD;
&#xD;
        -  sentinel lymph node biopsy as part of their normal care&#xD;
&#xD;
        -  resection of metastatic skin lesions or visceral disease&#xD;
&#xD;
        -  medical treatment for Stage IV disease Biospecimens include urine, stool, saliva, hair&#xD;
           follicles, ascitic, pleural, pericardial or cerebrospinal fluid Collection of archival&#xD;
           tumour tissue from previous biopsy/surgery that is surplus to clinical requirements will&#xD;
           also be requested, where available.&#xD;
&#xD;
      Participants will be asked to consent to having easily accessible lesions biopsied or&#xD;
      resected, which are not required for clinical reasons, but are for research purposes only.&#xD;
      Participants can still be part of the study even if they do not agree to these extra,&#xD;
      optional biopsies. Tissue samples from the surgical specimens and the original primaries will&#xD;
      be examined to look for molecular markers to correlate with circulating tumour molecular&#xD;
      markers.&#xD;
&#xD;
      Consent will be requested to grow cell lines from the donated tumour tissue and implant&#xD;
      tumour tissue into mice to characterise the genetic changes seen in both CTCs and biopsies,&#xD;
      in terms of resistance to targeted agents, in the lab setting. Consent to this part of the&#xD;
      study will be optional.&#xD;
&#xD;
      A maximum of 50mls blood sample will be requested from participants before any intervention.&#xD;
      Further blood samples (maximum of 50mls each time) will also be requested as follows:&#xD;
&#xD;
        -  after surgery, on subsequent routine follow up at 3 months, and then 3 monthly&#xD;
           thereafter (i.e. approximately 4 times in a year after the initial pre and post surgical&#xD;
           specimens)&#xD;
&#xD;
        -  at the time of disease recurrence&#xD;
&#xD;
        -  If on treatment, then usually approximately 3 weeks after starting treatment, and then&#xD;
           every 2 cycles of treatment&#xD;
&#xD;
        -  at disease progression The samples will be tested for various circulating tumour&#xD;
           biomarkers.&#xD;
&#xD;
      We will be asking a small group of patients, approx 20, to consent to weekly blood samples,&#xD;
      for up to 8 weeks, for specific biomarker analyses.&#xD;
&#xD;
      Clinical data will be collected for each patient, looking at demographics, baseline&#xD;
      haematology and biochemistry blood results, radiological extent of disease, time to disease&#xD;
      progression, clinical and histological features of the primary. Patients will be followed up&#xD;
      for approximately 10 years to assess their outcome.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 14, 2018</start_date>
  <completion_date type="Anticipated">July 2034</completion_date>
  <primary_completion_date type="Anticipated">July 2034</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>Other</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>The number of patients who consent to have additional samples taken for research purposes and the number of research samples collected.</measure>
    <time_frame>Duration of study, 300 participants over 16 years</time_frame>
    <description>This is primarily a sample collection study, where tissue will be used in future experiments to further understand mechanisms of disease resistance. This study will however assess patients acceptability to enrol in a study, where biological samples are taken purely for research, and not part of routine care.</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Melanoma</condition>
  <arm_group>
    <arm_group_label>All participants</arm_group_label>
    <description>All eligible, consented participants, will be asked to give blood, tissue, and other biospecimens for research purposes</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Surgery</intervention_name>
    <description>To collect tumour tissue</description>
    <arm_group_label>All participants</arm_group_label>
    <other_name>Biopsy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Venepuncture</intervention_name>
    <description>To collect blood samples</description>
    <arm_group_label>All participants</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Tumour biopsies, whole blood and blood products&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with stage III or IV melanoma undergoing systemic therapy at The Christie hospital&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age of 16 years or more.&#xD;
&#xD;
          2. Patients must have given written informed consent.&#xD;
&#xD;
          3. Evidence of locally advanced or metastatic melanoma, i.e. stage III or IV disease.&#xD;
&#xD;
          4. Accessible tumour that can be safely biopsied using radiological or surgical&#xD;
             techniques (if consenting to part A).&#xD;
&#xD;
          5. Full blood count and coagulation tests within acceptable parameters (if consenting to&#xD;
             part A).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Inability to provide informed consent.&#xD;
&#xD;
          2. History of significant bleeding disorder (patients on anticoagulation are eligible if&#xD;
             the anticoagulation can be safely managed to allow fresh tumour biopsies and blood&#xD;
             sampling).&#xD;
&#xD;
          3. History of HIV, Hepatitis B/C or other transmissible human disease.&#xD;
&#xD;
          4. Any conditions where research biopsies or blood sampling may increase risk of&#xD;
             complications for the patient and/or investigator, including high risk groups such as&#xD;
             intravenous drug users.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lorigan, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Manchester</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Gupta, Dr</last_name>
    <phone>0161 446 3472</phone>
    <email>avinash.gupta@christie.nhs.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Valpione, Dr</last_name>
    <email>sara.valpione@christie.nhs.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The Christie</name>
      <address>
        <city>Manchester</city>
        <zip>M20 4BX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dr Gupta</last_name>
      <phone>0161 446 3472</phone>
    </contact>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 21, 2020</study_first_submitted>
  <study_first_submitted_qc>July 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 30, 2020</study_first_posted>
  <last_update_submitted>July 29, 2020</last_update_submitted>
  <last_update_submitted_qc>July 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Tumour Biopsy</keyword>
  <keyword>Blood Biomarker</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>No plans to share IPD</ipd_description>
  </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/NCT04493723
org study id: CFTSp157
secondary id: 18/NW/0515
secondary id: 132792
nct id: NCT04493723
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Recent advances in understanding how cancer develops and spreads have led to effective new
      treatments and improved outcomes for patients with melanoma. However, we know that these new
      treatments do not work for all patients: some do not respond to them and some initially
      respond but then develop resistance. The overall aim of this study will be to collect tumour
      biopsies, biomarkers present in the blood, and other biological specimens which can be used
      to try to understand why resistance to anti-cancer treatment occurs, and to develop
      predictive biomarkers of this resistance in patients with locally advanced and metastatic
      malignant melanoma.

      The study will be open to NHS patients aged 16 and over, who have been diagnosed with
      advanced melanoma, and who will be receiving treatment for their disease as part of their
      routine care. Patients will be asked to provide samples from tumour biopsies before, during
      and after treatment. We will also ask for blood samples to look at biomarkers in the blood
      and see how these correspond with tumour samples, which will further help us to understand
      treatment response. Biomarkers are substances in the body that can be measured and help
      indicate how a disease is developing. It is hoped that soon we will be able to monitor cancer
      by analysing a patient's blood samples, thus reducing the need for biopsies. As blood tests
      could be taken more frequently, signs that patients are becoming resistant to treatments
      could be picked up sooner.

      As well as monitoring biomarkers, we would also like to understand what happens to the
      healthy cells surrounding the tumour during treatment. This will improve our understanding of
      how cells adapt and respond to treatments, and may eventually lead to the discovery of new
      biomarkers to help predict which patients will develop resistance to certain treatments.
This will be a prospective study recruiting patients who have been diagnosed wth advanced
      melanoma.

      Participants will be asked to give informed consent before any samples are collected.

      Participants will be asked to donate tissue and other biospecimens (see list below) that are
      surplus to clinical requirements if a participant is undergoing any of the following as part
      of their routine care:

        -  lymph node dissection

        -  sentinel lymph node biopsy as part of their normal care

        -  resection of metastatic skin lesions or visceral disease

        -  medical treatment for Stage IV disease Biospecimens include urine, stool, saliva, hair
           follicles, ascitic, pleural, pericardial or cerebrospinal fluid Collection of archival
           tumour tissue from previous biopsy/surgery that is surplus to clinical requirements will
           also be requested, where available.

      Participants will be asked to consent to having easily accessible lesions biopsied or
      resected, which are not required for clinical reasons, but are for research purposes only.
      Participants can still be part of the study even if they do not agree to these extra,
      optional biopsies. Tissue samples from the surgical specimens and the original primaries will
      be examined to look for molecular markers to correlate with circulating tumour molecular
      markers.

      Consent will be requested to grow cell lines from the donated tumour tissue and implant
      tumour tissue into mice to characterise the genetic changes seen in both CTCs and biopsies,
      in terms of resistance to targeted agents, in the lab setting. Consent to this part of the
      study will be optional.

      A maximum of 50mls blood sample will be requested from participants before any intervention.
      Further blood samples (maximum of 50mls each time) will also be requested as follows:

        -  after surgery, on subsequent routine follow up at 3 months, and then 3 monthly
           thereafter (i.e. approximately 4 times in a year after the initial pre and post surgical
           specimens)

        -  at the time of disease recurrence

        -  If on treatment, then usually approximately 3 weeks after starting treatment, and then
           every 2 cycles of treatment

        -  at disease progression The samples will be tested for various circulating tumour
           biomarkers.

      We will be asking a small group of patients, approx 20, to consent to weekly blood samples,
      for up to 8 weeks, for specific biomarker analyses.

      Clinical data will be collected for each patient, looking at demographics, baseline
      haematology and biochemistry blood results, radiological extent of disease, time to disease
      progression, clinical and histological features of the primary. Patients will be followed up
      for approximately 10 years to assess their outcome.
observational model: Other
time perspective: Other
measure: The number of patients who consent to have additional samples taken for research purposes and the number of research samples collected.
time frame: Duration of study, 300 participants over 16 years
description: This is primarily a sample collection study, where tissue will be used in future experiments to further understand mechanisms of disease resistance. This study will however assess patients acceptability to enrol in a study, where biological samples are taken purely for research, and not part of routine care.
arm group label: All participants
description: All eligible, consented participants, will be asked to give blood, tissue, and other biospecimens for research purposes
intervention type: Procedure
intervention name: Surgery
description: To collect tumour tissue
arm group label: All participants
other name: Biopsy
intervention type: Procedure
intervention name: Venepuncture
description: To collect blood samples
arm group label: All participants
Tumour biopsies, whole blood and blood products
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 16 Years
maximum age: N/A
healthy volunteers: No
last name: Lorigan, Prof
role: Principal Investigator
affiliation: University of Manchester
last name: Gupta, Dr
phone: 0161 446 3472
email: avinash.gupta@christie.nhs.uk
last name: Valpione, Dr
email: sara.valpione@christie.nhs.uk
facility: 
status: Recruiting
contact: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Melanoma
sharing ipd: No
ipd description: No plans to share IPD