<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/NCT02994888</url>
  </required_header>
  <id_info>
    <org_study_id>3770</org_study_id>
    <nct_id>NCT02994888</nct_id>
  </id_info>
  <brief_title>PROSPECT-C: A Study of Biomarkers of Response or Resistance to Anti-EGFR Therapies in Metastatic Colorectal Cancer</brief_title>
  <acronym>PROSPECT-C</acronym>
  <official_title>PROSPECT-C: A Prospective Translational Study Investigating Molecular Predictors of Resistance and Response to Cetuximab or Panitumumab in Metastatic Colorectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Royal Marsden NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Royal Marsden NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      PROSPECT-C is a phase II study investigating the molecular markers of response or resistance&#xD;
      to anti-epidermal growth factor receptor (EGFR) antibodies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cetuximab or panitumumab are two monoclonal antibodies that are routinely offered to patients&#xD;
      with metastatic colorectal cancer when they have no mutation in RAS genes. In Royal Marsden&#xD;
      Hospital patients, who are refractory to all standard therapies and have metastatic&#xD;
      colorectal cancer are offered one of these agents in third line metastatic setting. Whilst&#xD;
      the mechanisms of response/resistance to these therapies are well studies, they are still&#xD;
      incompletely understood. The main hypothesis of this study is that finding mechanisms of&#xD;
      response and/or resistance by using novel techniques such as next generation sequencing (NGS)&#xD;
      and/or digital droplet polymerase chain reaction (ddPCR) to these therapies will allow better&#xD;
      patient selection and application of precision medicine in such patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">December 2016</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>Track and validate specific known mechanisms of resistance/response to anti-EGFR therapies through</measure>
    <time_frame>3-4 years</time_frame>
    <description>digital droplet polymerase chain reaction (ddPCR) and ultra deep next generation sequencing (NGS) analyses of circulating tumour deoxyribonucleic acid (ct-DNA) obtained every 4 weeks during the course of treatment. Mutations found in ctDNA will also be analysed in the archival and fresh tissue specimens, used for diagnostic testing and obtained during the study respectively</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Identify novel biomarkers of resistance to anti-EGFR therapies through whole exome sequencing</measure>
    <time_frame>3-4 years</time_frame>
    <description>DNA extracted from pre- and post-treatment metastatic colorectal cancer (mCRC) biopsies; Ultra deep targeted sequencing of tumour samples and of ctDNA will be used to assess whether the identified resistance biomarkers are detectable in some patients before treatment initiation and whether this correlates with short progression free survival (PFS) and poor radiological response</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">47</enrollment>
  <condition>Metastatic Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>all patients</arm_group_label>
    <description>All patients will be treated with cetuximab 500mg/m2 every 2 weeks until the time of progression</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cetuximab</intervention_name>
    <description>All patients will be offered cetuximab 500mg/m2 every 2 weeks, until the time of progression</description>
    <arm_group_label>all patients</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Both fresh frozen tissue and formalin-fixed paraffin-embedded (FFPE) tissue samples will be&#xD;
      obtained. In addition, the following blood samples will also be taken;&#xD;
&#xD;
        1. Baseline: an initial 20mL research blood sample (EDTA or equivalent (CPT) tube) will be&#xD;
           collected&#xD;
&#xD;
        2. Every 4 weeks until disease progression or patient death: 1 x 10mL research blood sample&#xD;
           (EDTA or equivalent (CPT) tube) will be collected&#xD;
&#xD;
        3. At time of progressive disease: final 10mL research blood sample (EDTA or equivalent&#xD;
           (CPT) tube)&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        patients with a histologically confirmed diagnosis of metastatic colorectal adenocarcinoma&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. patients with a histologically confirmed diagnosis of metastatic colorectal&#xD;
             adenocarcinoma&#xD;
&#xD;
          2. wild-type RAS tumour status by molecular analysis at the Royal Marsden Hospital&#xD;
&#xD;
          3. patients with inoperable metastatic colorectal cancer who are scheduled to be treated&#xD;
             with cetuximab (or panitumumab) either as monotherapy or in combination with&#xD;
             chemotherapy with palliative intent&#xD;
&#xD;
          4. patients who have received prior treatment with oxaliplatin, irinotecan and&#xD;
             fluoropyrimidine containing chemotherapy regimens OR intolerance/contraindication to&#xD;
             either oxaliplatin or irinotecan based chemotherapy, and planned to receive&#xD;
             retreatment with EGFR monoclonal antibody (mAB) monotherapy or with EGFR mAB combined&#xD;
             with a chemotherapy (irinotecan or oxaliplatin-based) that a patient has already&#xD;
             received for a minimum of 3 months during a previous line of therapy.&#xD;
&#xD;
          5. patients who have metastatic disease sites which are amenable to core biopsy&#xD;
             (preferably liver, soft tissue or nodal disease, with at least one lesion 3cm or more&#xD;
             in diameter. If largest lesion 2-3cm diameter, eligibility to be discussed with&#xD;
             radiologist prior to study entry)&#xD;
&#xD;
          6. patients aged 18 years or older&#xD;
&#xD;
          7. able to provide fully informed consent, to comply with the trial and follow-up&#xD;
             procedures&#xD;
&#xD;
          8. receiving treatment at the Royal Marsden Hospital&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. patients who have previously received treatment with cetuximab or panitumumab&#xD;
&#xD;
          2. previous malignancy other than colorectal cancer in the past 5 years, other than&#xD;
             pre-invasive malignancy of the cervix or basal cell carcinoma, EXCEPT when the patient&#xD;
             has histological confirmation of metastatic colorectal cancer at the site that is&#xD;
             planned to be biopsied at baseline and on progression of disease&#xD;
&#xD;
          3. patients who are being anti-coagulated with warfarin or heparin&#xD;
&#xD;
          4. Patients that are participating in another clinical trial involving an investigational&#xD;
             medicinal product, unless it is more than 14 days after they have ceased the&#xD;
             investigational medicinal product&#xD;
&#xD;
          5. Patients that are participating in another research study involving tumour tissue&#xD;
             biopsies planned to take place during the time that the patient is participating in&#xD;
             this study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>The Royal Marsden NHS Foundation Trust</name>
      <address>
        <city>Surrey</city>
        <state>Sutton</state>
        <zip>SM2 5PT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>May 30, 2013</study_first_submitted>
  <study_first_submitted_qc>December 13, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 16, 2016</study_first_posted>
  <last_update_submitted>December 16, 2016</last_update_submitted>
  <last_update_submitted_qc>December 16, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 19, 2016</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>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cetuximab</mesh_term>
  </intervention_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/NCT02994888
org study id: 3770
nct id: NCT02994888
lead sponsor: 
has dmc: No
PROSPECT-C is a phase II study investigating the molecular markers of response or resistance
      to anti-epidermal growth factor receptor (EGFR) antibodies.
Cetuximab or panitumumab are two monoclonal antibodies that are routinely offered to patients
      with metastatic colorectal cancer when they have no mutation in RAS genes. In Royal Marsden
      Hospital patients, who are refractory to all standard therapies and have metastatic
      colorectal cancer are offered one of these agents in third line metastatic setting. Whilst
      the mechanisms of response/resistance to these therapies are well studies, they are still
      incompletely understood. The main hypothesis of this study is that finding mechanisms of
      response and/or resistance by using novel techniques such as next generation sequencing (NGS)
      and/or digital droplet polymerase chain reaction (ddPCR) to these therapies will allow better
      patient selection and application of precision medicine in such patients.
observational model: Cohort
time perspective: Prospective
measure: Track and validate specific known mechanisms of resistance/response to anti-EGFR therapies through
time frame: 3-4 years
description: digital droplet polymerase chain reaction (ddPCR) and ultra deep next generation sequencing (NGS) analyses of circulating tumour deoxyribonucleic acid (ct-DNA) obtained every 4 weeks during the course of treatment. Mutations found in ctDNA will also be analysed in the archival and fresh tissue specimens, used for diagnostic testing and obtained during the study respectively
measure: Identify novel biomarkers of resistance to anti-EGFR therapies through whole exome sequencing
time frame: 3-4 years
description: DNA extracted from pre- and post-treatment metastatic colorectal cancer (mCRC) biopsies; Ultra deep targeted sequencing of tumour samples and of ctDNA will be used to assess whether the identified resistance biomarkers are detectable in some patients before treatment initiation and whether this correlates with short progression free survival (PFS) and poor radiological response
arm group label: all patients
description: All patients will be treated with cetuximab 500mg/m2 every 2 weeks until the time of progression
intervention type: Drug
intervention name: Cetuximab
description: All patients will be offered cetuximab 500mg/m2 every 2 weeks, until the time of progression
arm group label: all patients
Both fresh frozen tissue and formalin-fixed paraffin-embedded (FFPE) tissue samples will be
      obtained. In addition, the following blood samples will also be taken;

        1. Baseline: an initial 20mL research blood sample (EDTA or equivalent (CPT) tube) will be
           collected

        2. Every 4 weeks until disease progression or patient death: 1 x 10mL research blood sample
           (EDTA or equivalent (CPT) tube) will be collected

        3. At time of progressive disease: final 10mL research blood sample (EDTA or equivalent
           (CPT) tube)
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Cetuximab