<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/NCT01668680</url>
  </required_header>
  <id_info>
    <org_study_id>EMC-0047-11</org_study_id>
    <nct_id>NCT01668680</nct_id>
  </id_info>
  <brief_title>Maintenance Metronomic Chemotherapy for Metastatic Colorectal Carcinoma</brief_title>
  <official_title>Metronomic Chemotherapy With Anti-angiogenic Effect as Maintenance Treatment for Metastatic Colorectal Carcinoma Following Response to FOLFIRI+Bevacizumab: Clinical and Laboratory Studies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>HaEmek Medical Center, Israel</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Clalit Health Services</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>HaEmek Medical Center, Israel</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Colorectal cancer patients with metastases (mCRC) at response under expensive chemotherapy&#xD;
      which may be toxic +/- exhausting are candidates for an effective and more convenient&#xD;
      maintenance treatment.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
        1. To define the efficacy of maintenance chemotherapy by a low-dose metronomic (LDM)&#xD;
           regimen, in metastatic CRC patients responding under FOLFIRI + bevacizumab.&#xD;
&#xD;
        2. To discover predictive factors for response to this LDM regimen.&#xD;
&#xD;
      Hypothesis:&#xD;
&#xD;
        1. The re-growth of residual metastases can be slowed by the anti-angiogenic effects of LDM&#xD;
           chemotherapy.&#xD;
&#xD;
        2. Serial measurements of angiogenic/ inflammatory factors in the plasma and/or evaluation&#xD;
           of certain enzymes in the tumor may discover predictive factors of response to LDM&#xD;
           chemotherapy in metastatic CRC patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      At entry to the research protocol the up-till then administered treatment with Intra Venous&#xD;
      FOLFIRI+BEVACIZUMAB will be stopped.Instead, the research oral treatment will be initiated to&#xD;
      be taken daily on an ambulatory basis and under once monthly re-evaluation. If and when&#xD;
      disease progresses the original FOLFIRI+BEVACIZUMAB treatment will be considered for&#xD;
      re-institution.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    No satisfactory acrual&#xD;
  </why_stopped>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">December 2013</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Length of progression free survival (PFS), measured in months.</measure>
    <time_frame>Up to 12 months.</time_frame>
    <description>From start of the experimental treatment until the date of first documented progression or date of death of any cause,whichever came first, assessed up to 12 months.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Toxicity profile of treatment, defined by CTCAE Version 4.0.</measure>
    <time_frame>up to12 months</time_frame>
    <description>From start of the experimental treatment until the date of first documented progression or date of death of any cause,whichever came first, assessed up to 12 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in levels of angiogenic factors while under treatment: VEGF, PDGF, TSP-1</measure>
    <time_frame>Up to 4 months.</time_frame>
    <description>Change from baseline in levels of angiogenic factors at 4 months of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life, as expressed by FACT-C.</measure>
    <time_frame>Up to 12 months.</time_frame>
    <description>Change from baseline in parameters of Quality of life until the end of treatment, assessed up to 12 months.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Colorectal Cancer Metastatic</condition>
  <arm_group>
    <arm_group_label>LDM anti-angiogenic chemotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>LDM (Low Dose Metronomic) anti-angiogenic chemotherapy includes daily oral treatment with CAPECITABINE, CELECOXIB and METHOTREXATE.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>observation</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>observation only</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CAPECITABINE, CELECOXIB and METHOTREXATE</intervention_name>
    <description>daily oral treatment with CAPECITABINE, CELECOXIB and METHOTREXATE</description>
    <arm_group_label>LDM anti-angiogenic chemotherapy</arm_group_label>
    <other_name>Metronomic Chemotherapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologic (or cytologic) proof of colorectal carcinoma (CRC).&#xD;
&#xD;
          2. Age: between 18 and 80.&#xD;
&#xD;
          3. Sex: both sexes.&#xD;
&#xD;
          4. Previous treatment for metastatic disease is limited to FOLFIRI+ bevacizumab.&#xD;
&#xD;
          5. Prior adjuvant chemotherapy, with a fluoropyrimidine and/or Oxaliplatin, is allowed.&#xD;
&#xD;
          6. Prior radiotherapy, either as adjuvant treatment or palliation of metastatic sites is&#xD;
             allowed, provided that there are other non-irradiated foci of disease for evaluation.&#xD;
&#xD;
          7. Persistent remission, either complete, partial or minimal response (CR, PR or MR) or&#xD;
             stable disease (SD), one year+/-one month from initiation of first line treatment for&#xD;
             mCRC.&#xD;
&#xD;
          8. Asymptomatic patients at break from chemotherapy.&#xD;
&#xD;
          9. Intact organ function, including complete blood counts (CBC) showing normal values or&#xD;
             any toxicity limited to grade 1 and blood chemistry (SMA) showing liver and renal&#xD;
             functions &lt; 1.5 upper normal limit (UNL).&#xD;
&#xD;
         10. Capability to understand and to sign the informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Concurrent any other cancer (except BCC or squamous cell carcinoma of skin).&#xD;
&#xD;
          2. Inability to adhere to monthly visits to the oncology unit for evaluation.&#xD;
&#xD;
          3. Presence of brain metastases.&#xD;
&#xD;
          4. Any current or recent (within the last month) continuous treatment by steroids or by&#xD;
             NSAIDs, or with therapeutic doses of anticoagulants for any reason.&#xD;
&#xD;
          5. Previous radiotherapy to the only site of measurable disease.&#xD;
&#xD;
          6. Evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated&#xD;
             respiratory, cardiac including arrhythmias, hepatic or renal disease), and/or&#xD;
             existence of active peptic ulcer (clinically and/or by gastroscopy).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David Loven, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ha'Emek MC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>HaEmek Medical Center</name>
      <address>
        <city>Afula</city>
        <zip>18101</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>July 2015</verification_date>
  <study_first_submitted>March 11, 2012</study_first_submitted>
  <study_first_submitted_qc>August 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2012</study_first_posted>
  <last_update_submitted>July 6, 2015</last_update_submitted>
  <last_update_submitted_qc>July 6, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 8, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Metronomic Chemotherapy</keyword>
  <keyword>Anti-Angiogenic</keyword>
  <keyword>Maintenance Treatment</keyword>
  <keyword>Colorectal Cancer Metastatic</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>Celecoxib</mesh_term>
    <mesh_term>Capecitabine</mesh_term>
    <mesh_term>Methotrexate</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/NCT01668680
org study id: EMC-0047-11
nct id: NCT01668680
lead sponsor: 
collaborator: 
has dmc: No
Colorectal cancer patients with metastases (mCRC) at response under expensive chemotherapy
      which may be toxic +/- exhausting are candidates for an effective and more convenient
      maintenance treatment.

      Objectives:

        1. To define the efficacy of maintenance chemotherapy by a low-dose metronomic (LDM)
           regimen, in metastatic CRC patients responding under FOLFIRI + bevacizumab.

        2. To discover predictive factors for response to this LDM regimen.

      Hypothesis:

        1. The re-growth of residual metastases can be slowed by the anti-angiogenic effects of LDM
           chemotherapy.

        2. Serial measurements of angiogenic/ inflammatory factors in the plasma and/or evaluation
           of certain enzymes in the tumor may discover predictive factors of response to LDM
           chemotherapy in metastatic CRC patients.
At entry to the research protocol the up-till then administered treatment with Intra Venous
      FOLFIRI+BEVACIZUMAB will be stopped.Instead, the research oral treatment will be initiated to
      be taken daily on an ambulatory basis and under once monthly re-evaluation. If and when
      disease progresses the original FOLFIRI+BEVACIZUMAB treatment will be considered for
      re-institution.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Length of progression free survival (PFS), measured in months.
time frame: Up to 12 months.
description: From start of the experimental treatment until the date of first documented progression or date of death of any cause,whichever came first, assessed up to 12 months.
measure: Toxicity profile of treatment, defined by CTCAE Version 4.0.
time frame: up to12 months
description: From start of the experimental treatment until the date of first documented progression or date of death of any cause,whichever came first, assessed up to 12 months.
measure: Changes in levels of angiogenic factors while under treatment: VEGF, PDGF, TSP-1
time frame: Up to 4 months.
description: Change from baseline in levels of angiogenic factors at 4 months of treatment.
measure: Quality of life, as expressed by FACT-C.
time frame: Up to 12 months.
description: Change from baseline in parameters of Quality of life until the end of treatment, assessed up to 12 months.
arm group label: LDM anti-angiogenic chemotherapy
arm group type: Experimental
description: LDM (Low Dose Metronomic) anti-angiogenic chemotherapy includes daily oral treatment with CAPECITABINE, CELECOXIB and METHOTREXATE.
arm group label: observation
arm group type: No Intervention
description: observation only
intervention type: Drug
intervention name: CAPECITABINE, CELECOXIB and METHOTREXATE
description: daily oral treatment with CAPECITABINE, CELECOXIB and METHOTREXATE
arm group label: LDM anti-angiogenic chemotherapy
other name: Metronomic Chemotherapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: David Loven, MD
role: Principal Investigator
affiliation: Ha'Emek MC
facility: 
country: Israel
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Celecoxib
mesh term: Capecitabine
mesh term: Methotrexate