<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/NCT03264274</url>
  </required_header>
  <id_info>
    <org_study_id>9301</org_study_id>
    <secondary_id>2014-002003-25</secondary_id>
    <nct_id>NCT03264274</nct_id>
  </id_info>
  <brief_title>Trial of Aflibercept Monotherapy With DCE-US in Chemorefractory Metastatic Colorectal Cancer</brief_title>
  <acronym>AUSCOR</acronym>
  <official_title>A Phase II Trial of Aflibercept Monotherapy With Early Dynamic Contrast Enhanced Ultrasound Monitoring in Chemorefractory Metastatic Colorectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Barts &amp; The London NHS Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Barts &amp; The London NHS 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>
      Various antiangiogenic agents have a modest effect in prolonging overall survival in solid&#xD;
      tumours. In colorectal cancer it is clear that there are some patients in whom bevacizumab&#xD;
      significantly prolongs survival, but it is not effective in the majority of patients.&#xD;
      Biomarker studies using tumour tissue and blood have failed to define a consistent biomarker&#xD;
      that correlates with a beneficial effect of bevacizumab on survival. DCE-MRI can detect&#xD;
      changes in tumour blood flow which, in early phase drug studies, correlated with subsequent&#xD;
      tumour responses, but is too expensive and time consuming to be used in larger scale trials.&#xD;
      DCE-US is a promising biomarker for use in this group of patients with antiangiogenic agents,&#xD;
      as detailed above. The investigators wish to use this technique as a predictive biomarker for&#xD;
      any effects Aflibercept has on OS and PFS in patients with metastatic colorectal cancer&#xD;
      refractory to standard treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Funding restrictions - study never opened to recruitment&#xD;
  </why_stopped>
  <start_date type="Actual">February 6, 2017</start_date>
  <completion_date type="Actual">February 6, 2017</completion_date>
  <primary_completion_date type="Actual">February 6, 2017</primary_completion_date>
  <phase>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>
    <intervention_model_description>Single arm study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>No masking</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Overall survival</measure>
    <time_frame>1 year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>Aflibercept + DCE-US</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Aflibercept: 4mg/kg IV every 2 weeks until discontinuation due to progression. DCE-US before treatment, and at 2 weeks and 8 weeks after the first Aflibercept administration.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aflibercept</intervention_name>
    <description>Antiangiogenic</description>
    <arm_group_label>Aflibercept + DCE-US</arm_group_label>
    <other_name>Zaltrap</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Dynamic Contrast Enhanced Ultrasound</intervention_name>
    <description>DCE-US (a technique using differential liver blood flow assessments using microbubble) will be performed at baseline, Week 2 and 8 of treatment.</description>
    <arm_group_label>Aflibercept + DCE-US</arm_group_label>
    <other_name>DCE-US</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
        1. Histologically or cytologically confirmed adenocarcinoma of the colon or rectum with&#xD;
        liver metastasis(es), at least one of which should not have had any focal therapy including&#xD;
        radiofrequency ablation.&#xD;
&#xD;
        2. Evidence of uni-dimensionally measurable disease as defined by the Response Evaluation&#xD;
        Criteria in Solid Tumours (RECIST).&#xD;
&#xD;
        3. 18 years of age or older.&#xD;
&#xD;
        4. ECOG performance status of &lt; 3.&#xD;
&#xD;
        5. Failed (or intolerant of) at least 2 chemotherapy regimens in advanced disease and&#xD;
        resolution of any acute toxic effects of prior therapy e.g. radiotherapy or surgical&#xD;
        procedure to NCI CTCv4 grade ≤1. No other alternative available effective treatment&#xD;
        options.&#xD;
&#xD;
        6. Adequate organ function as defined by the following criteria:&#xD;
&#xD;
          -  Serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) ≤5 x&#xD;
             upper limit of normal (ULN).&#xD;
&#xD;
          -  Total serum bilirubin &lt;1.5 x ULN&#xD;
&#xD;
          -  Serum albumin ≥25mg/dl&#xD;
&#xD;
          -  Absolute neutrophil count ≥1000/µL&#xD;
&#xD;
          -  Platelets ≥75, 000/µL&#xD;
&#xD;
          -  Haemoglobin ≥9.0 g/dL&#xD;
&#xD;
          -  Serum creatinine ≤1.5 x ULN&#xD;
&#xD;
             7. Willingness and ability to provide fully informed consent to participate in the&#xD;
             study.&#xD;
&#xD;
             8. Willingness and ability to comply with scheduled visits, treatment plans,&#xD;
             laboratory tests, and other study procedures.&#xD;
&#xD;
             9. Willingness to maintain good oral hygiene and receive regular dental assessments.&#xD;
             No evidence of oral infection or planned dental surgery (excluding fillings).&#xD;
&#xD;
             10. Willingness to donate archival diagnostic tissue for translational research.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Palliative radiotherapy to non-target, metastatic lesions will be allowed.&#xD;
&#xD;
          2. Less than 4 weeks following major surgery to the time of inclusion or until the&#xD;
             surgical wound is fully healed, whichever came later (48 hours in case of minor&#xD;
             surgical procedure or until wound full healing observed).&#xD;
&#xD;
          3. Less than 4 weeks elapsed from prior radiotherapy or prior chemotherapy to the time of&#xD;
             inclusion.&#xD;
&#xD;
          4. Treatment with any investigational drug within 30 days prior to inclusion.&#xD;
&#xD;
          5. Adverse events (with exception of alopecia, peripheral sensory neuropathy and those&#xD;
             listed in specific exclusion criteria) from any prior anti-cancer therapy of grade &gt;1&#xD;
             (National Cancer Institute Common terminology Criteria [NCI CTCAE] v.4.0) at the time&#xD;
             of inclusion.&#xD;
&#xD;
          6. History of brain metastases, uncontrolled spinal cord compression, or carcinomatous&#xD;
             meningitis or new evidence of brain or leptomeningeal disease.&#xD;
&#xD;
          7. Other prior malignancy, with the exception of adequately treated basal cell or&#xD;
             squamous cell skin cancer, carcinoma in situ of the cervix or any other cancer from&#xD;
             which the patient has been disease free for &gt; 5 years.&#xD;
&#xD;
          8. Any of the following within 6 months prior to inclusion: myocardial infarction,&#xD;
             severe/unstable angina pectoris, coronary/peripheral artery bypass graft, NYHA class&#xD;
             III or IV congestive heart failure, stroke or transient ischemic attack.&#xD;
&#xD;
          9. Any of the following within 3 months prior to inclusion: Grade 3-4 gastrointestinal&#xD;
             bleeding/haemorrhage, treatment resistant peptic ulcer disease, erosive oesophagitis&#xD;
             or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary&#xD;
             embolism or other uncontrolled thromboembolic event.&#xD;
&#xD;
         10. Known acquired immunodeficiency syndrome (AIDS-related illnesses) or known HIV disease&#xD;
             requiring antiretroviral treatment.&#xD;
&#xD;
         11. Any severe acute or chronic medical condition, which could impair the ability of the&#xD;
             patient to participate to the study or to interfere with interpretation of study&#xD;
             results.&#xD;
&#xD;
         12. Predisposing colonic or small bowel disorders in which the symptoms were uncontrolled&#xD;
             as indicated by baseline of &gt; 3 loose stools daily.&#xD;
&#xD;
         13. Treatment with concomitant anticonvulsant agents that are CYP3A4 inducers (phenytoin,&#xD;
             phenobarbital, carbamazepine), unless discontinued &gt;7 days.&#xD;
&#xD;
         14. Pregnant or breast-feeding women. Positive pregnancy test (serum or urine β-HCG) for&#xD;
             women of reproductive potential.&#xD;
&#xD;
         15. Patients with reproductive potential (female and male) who do not agree to use an&#xD;
             accepted effective method of contraception during the study treatment period and for&#xD;
             at least 6 months following completion of study treatment. Effective method is defined&#xD;
             in section 12.16.&#xD;
&#xD;
         16. Urine protein-creatinine ratio (UPCR) &gt;1 on morning spot urinalysis or proteinuria &gt;&#xD;
             500 mg/24-h.&#xD;
&#xD;
         17. Serum creatinine &gt; 1.5 x upper limit of normal (ULN).&#xD;
&#xD;
         18. Uncontrolled hypertension (defined as blood pressure &gt; 140/90 mmHg or systolic blood&#xD;
             pressure &gt;160 mmHg when diastolic blood pressure &lt; 90 mmHg, on at least 2 repeated&#xD;
             determinations on separate days, or upon clinical judgment) within 3 months prior to&#xD;
             study inclusion.&#xD;
&#xD;
         19. Patients on anticoagulant therapy with unstable dose of warfarin and/or having an&#xD;
             out-of-therapeutic range INR (&gt;3) within the 4 weeks prior to inclusion.&#xD;
&#xD;
         20. Evidence of clinically significant bleeding diathesis or underlying coagulopathy (e.g.&#xD;
             INR&gt;1.5 without vitamin K antagonist therapy), non-healing wound.&#xD;
&#xD;
         21. Allergy to sulphur.&#xD;
&#xD;
         22. Use of IV bisphosphonates or dental surgery in the previous 60 days, or any planned&#xD;
             use of IV bisphosphonates or dental surgery.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David David</last_name>
    <role>Principal Investigator</role>
    <affiliation>Barts &amp; The London NHS Trust</affiliation>
  </overall_official>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>March 31, 2016</study_first_submitted>
  <study_first_submitted_qc>August 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 29, 2017</study_first_posted>
  <last_update_submitted>August 30, 2017</last_update_submitted>
  <last_update_submitted_qc>August 30, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 31, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Colorectal</keyword>
  <keyword>Metastatic</keyword>
  <keyword>Chemorefractory</keyword>
  <keyword>Ultrasound</keyword>
  <keyword>Aflibercept</keyword>
  <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>Aflibercept</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>No data collected. Study closed before recruitment.</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/NCT03264274
org study id: 9301
secondary id: 2014-002003-25
nct id: NCT03264274
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Various antiangiogenic agents have a modest effect in prolonging overall survival in solid
      tumours. In colorectal cancer it is clear that there are some patients in whom bevacizumab
      significantly prolongs survival, but it is not effective in the majority of patients.
      Biomarker studies using tumour tissue and blood have failed to define a consistent biomarker
      that correlates with a beneficial effect of bevacizumab on survival. DCE-MRI can detect
      changes in tumour blood flow which, in early phase drug studies, correlated with subsequent
      tumour responses, but is too expensive and time consuming to be used in larger scale trials.
      DCE-US is a promising biomarker for use in this group of patients with antiangiogenic agents,
      as detailed above. The investigators wish to use this technique as a predictive biomarker for
      any effects Aflibercept has on OS and PFS in patients with metastatic colorectal cancer
      refractory to standard treatment.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Single arm study
primary purpose: Treatment
masking: None (Open Label)
masking description: No masking
measure: Overall survival
time frame: 1 year
measure: Progression-free survival
time frame: 1 year
arm group label: Aflibercept + DCE-US
arm group type: Other
description: Aflibercept: 4mg/kg IV every 2 weeks until discontinuation due to progression. DCE-US before treatment, and at 2 weeks and 8 weeks after the first Aflibercept administration.
intervention type: Drug
intervention name: Aflibercept
description: Antiangiogenic
arm group label: Aflibercept + DCE-US
other name: Zaltrap
intervention type: Procedure
intervention name: Dynamic Contrast Enhanced Ultrasound
description: DCE-US (a technique using differential liver blood flow assessments using microbubble) will be performed at baseline, Week 2 and 8 of treatment.
arm group label: Aflibercept + DCE-US
other name: DCE-US
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: David David
role: Principal Investigator
affiliation: Barts & The London NHS Trust
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Aflibercept
sharing ipd: No
ipd description: No data collected. Study closed before recruitment.