<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/NCT02970916</url>
  </required_header>
  <id_info>
    <org_study_id>TTD-16-02</org_study_id>
    <nct_id>NCT02970916</nct_id>
  </id_info>
  <brief_title>Phase II Trial to Assess FOLFIRI+Aflibercept Efficacy in Patients With Oxaliplatin-pretreated Metastatic Colorectal Cancer With or Without ACE Polymorphisms</brief_title>
  <acronym>POLAF</acronym>
  <official_title>A Phase II Trial to Assess FOLFIRI+Aflibercept Efficacy in Patients With Oxaliplatin-pretreated Metastatic Colorectal Cancer With or Without ACE Polymorphisms</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess FOLFIRI+aflibercept efficacy in patients with or&#xD;
      without ACE polymorphisms in terms of Progression-free survival (PFS).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2016</start_date>
  <completion_date type="Actual">December 2018</completion_date>
  <primary_completion_date type="Actual">May 2018</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>FOLFIRI+aflibercept efficacy in terms of Progression-free survival (PFS) with or without ACE polymorphisms.</measure>
    <time_frame>30 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS) with or without AGTR1 polymorphisms, according Serum-level sACE</measure>
    <time_frame>30 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE</measure>
    <time_frame>30 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE</measure>
    <time_frame>30 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to progression (TP) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE</measure>
    <time_frame>30 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to treatment failure (TTF) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE</measure>
    <time_frame>30 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE</measure>
    <time_frame>30 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with adverse events as assessed by CTCAE v4.0.</measure>
    <time_frame>30 months</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Plasma VEGF levels circulating and their correlation with tumour-efficacy parameters (ORR, PFS and OS)</measure>
    <time_frame>30 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Other biomarkers in serum and tumour tissue associated with cell and tumour growth and/or involved in the mechanism of action of FOLFIRI+aflibercept and their correlation with tumour-efficacy parameters (ORR, PFS and OS)</measure>
    <time_frame>30 months</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Metastatic Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>FOLFIRI+aflibercept</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FOLFIRI+aflibercept</intervention_name>
    <description>Aflibercept: 4 mg/kg administered intravenous infusion on day 1&#xD;
FOLFIRI regimen immediately after aflibercept:&#xD;
Irinotecan:180 mg/m2 intravenous infusion, folinic acid (dl racemic): 400 mg/m2 intravenous infusion, followed by 5-fluorouracil (5-FU): 400 mg/m2 intravenous bolus, followed by 5-FU: 2400 mg/m2 continuous intravenous infusion over 46 hours.&#xD;
* folinic acid: 400 mg/m² (racémic) or 200 mg/m² (L-form)</description>
    <arm_group_label>FOLFIRI+aflibercept</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed and dated informed consent, and willing and able to comply with protocol&#xD;
             requirements,&#xD;
&#xD;
          2. Histologically proven adenocarcinoma of the colon and/or rectum,&#xD;
&#xD;
          3. Metastatic disease confirmed.&#xD;
&#xD;
          4. Existence of at least one measurable unidimensional lesion using CT or MRI based on&#xD;
             the RECIST criteria, version 1.1&#xD;
&#xD;
          5. Patients with metastatic colorectal cancer (mCRC) that is resistant to or has&#xD;
             progressed after an oxaliplatin-containing regimen.&#xD;
&#xD;
          6. Age ≥18 years&#xD;
&#xD;
          7. World Health Organization (WHO) Performance status (PS) 0-2,&#xD;
&#xD;
          8. Hematological status: neutrophils (ANC) ≥1.5x109 /L; platelets ≥100x109 /L;&#xD;
             haemoglobin ≥9g/dL&#xD;
&#xD;
          9. Adequate renal function: serum creatinine level &lt; 1.5 x ULN&#xD;
&#xD;
         10. Adequate liver function: serum bilirubin ≤1.5 x upper normal limit (ULN), alkaline&#xD;
             phosphatase (ALP) &lt;5xULN&#xD;
&#xD;
         11. Proteinuria &lt;2+ (dipstick urinalysis) or ≤1g/24hour.&#xD;
&#xD;
         12. Regular follow-up feasible.&#xD;
&#xD;
         13. For female patients of childbearing potential, negative serum pregnancy test&#xD;
&#xD;
         14. Female patients must commit to using reliable and appropriate methods of contraception&#xD;
             until at least three months after the end of study treatment (when applicable). Male&#xD;
             patients with a partner of childbearing potential must agree to use contraception in&#xD;
             addition to having their partner use another contraceptive method during the trial.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Uncontrolled hypercalcemia,&#xD;
&#xD;
          2. Pre-existing permanent neuropathy (NCI grade &gt;2)&#xD;
&#xD;
          3. Uncontrolled hypertension (defined as systolic blood pressure &gt;150 mmHg and/or&#xD;
             diastolic blood pressure &gt;100 mmHg), or history of hypertensive crisis, or&#xD;
             hypertensive ncephalopathy,&#xD;
&#xD;
          4. Concomitant protocol unplanned antitumor therapy (e.g. chemotherapy, molecular&#xD;
             targeted therapy, immunotherapy),&#xD;
&#xD;
          5. Treatment with any other investigational medicinal product within 28 days prior to&#xD;
             study entry.&#xD;
&#xD;
          6. Other serious and uncontrolled non-malignant disease,&#xD;
&#xD;
          7. History or evidence upon physical examination of CNS metastasis unless adequately&#xD;
             treated (e.g. non irradiated CNS metastasis, seizure not controlled with standard&#xD;
             medical therapy),&#xD;
&#xD;
          8. Known Gilbert's syndrome&#xD;
&#xD;
          9. Intolerance to atropine sulfate or loperamide&#xD;
&#xD;
         10. Known dihydropyrimidine dehydrogenase deficiency&#xD;
&#xD;
         11. Treatment with CYP3A4 inducers unless discontinued &gt; 7 days prior to inclusion&#xD;
&#xD;
         12. Any of the following in 3 months prior to inclusion: grade 3-4 gastrointestinal&#xD;
             bleeding (unless due to resected tumor), treatment resistant peptic ulcer disease,&#xD;
             erosive esophagitis or gastritis, infectious or inflammatory bowel disease, or&#xD;
             diverticulitis.&#xD;
&#xD;
         13. Other concomitant or previous malignancy, except: i/ adequately treated insitu&#xD;
             carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin,&#xD;
             iii/ cancer in complete remission for &gt;5 years,&#xD;
&#xD;
         14. Any other serious and uncontrolled non-malignant disease, major surgery or traumatic&#xD;
             injury within the last 28 days&#xD;
&#xD;
         15. Pregnant or breastfeeding women,&#xD;
&#xD;
         16. Patients with known allergy to any excipient to study drugs,&#xD;
&#xD;
         17. History of myocardial infarction and/or stroke within 6 months prior to inclusion,&#xD;
             NYHA class III and IV congestive heart failure&#xD;
&#xD;
         18. Bowel obstruction.&#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>Enrique Aranda, MD-PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Hospital Universitario Reina Sofía</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Auxiliadora Gómez, MD-PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Hospital Universitario Reina Sofía</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Spanish Cooperative Group for the Treatment of Digestive Tumors</name>
      <address>
        <city>Madrona</city>
        <zip>28007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>November 16, 2016</study_first_submitted>
  <study_first_submitted_qc>November 18, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 22, 2016</study_first_posted>
  <last_update_submitted>April 10, 2019</last_update_submitted>
  <last_update_submitted_qc>April 10, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 11, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>metastatic colorectal cancer</keyword>
  <keyword>FOLFIRI</keyword>
  <keyword>aflibercept</keyword>
  <keyword>oxaliplatin</keyword>
  <keyword>ACE polymorphisms</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>
  <!-- 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/NCT02970916
org study id: TTD-16-02
nct id: NCT02970916
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to assess FOLFIRI+aflibercept efficacy in patients with or
      without ACE polymorphisms in terms of Progression-free survival (PFS).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: FOLFIRI+aflibercept efficacy in terms of Progression-free survival (PFS) with or without ACE polymorphisms.
time frame: 30 months
measure: Progression free survival (PFS) with or without AGTR1 polymorphisms, according Serum-level sACE
time frame: 30 months
measure: Objective Response Rate (ORR) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE
time frame: 30 months
measure: Disease Control Rate (DCR) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE
time frame: 30 months
measure: Time to progression (TP) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE
time frame: 30 months
measure: Time to treatment failure (TTF) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE
time frame: 30 months
measure: Overall survival (OS) with or without ACE polymorphisms, AGTR1 polymorphisms, according Serum-level sACE
time frame: 30 months
measure: Number of participants with adverse events as assessed by CTCAE v4.0.
time frame: 30 months
measure: Plasma VEGF levels circulating and their correlation with tumour-efficacy parameters (ORR, PFS and OS)
time frame: 30 months
measure: Other biomarkers in serum and tumour tissue associated with cell and tumour growth and/or involved in the mechanism of action of FOLFIRI+aflibercept and their correlation with tumour-efficacy parameters (ORR, PFS and OS)
time frame: 30 months
arm group label: FOLFIRI+aflibercept
arm group type: Experimental
intervention type: Drug
intervention name: FOLFIRI+aflibercept
description: Aflibercept: 4 mg/kg administered intravenous infusion on day 1
FOLFIRI regimen immediately after aflibercept:
Irinotecan:180 mg/m2 intravenous infusion, folinic acid (dl racemic): 400 mg/m2 intravenous infusion, followed by 5-fluorouracil (5-FU): 400 mg/m2 intravenous bolus, followed by 5-FU: 2400 mg/m2 continuous intravenous infusion over 46 hours.
* folinic acid: 400 mg/m² (racémic) or 200 mg/m² (L-form)
arm group label: FOLFIRI+aflibercept
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Enrique Aranda, MD-PhD
role: Study Chair
affiliation: Hospital Universitario Reina Sofía
last name: Auxiliadora Gómez, MD-PhD
role: Study Chair
affiliation: Hospital Universitario Reina Sofía
facility: 
country: Spain
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Aflibercept