<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/NCT01715441</url>
  </required_header>
  <id_info>
    <org_study_id>NEXIRI2</org_study_id>
    <secondary_id>2012-000644-94</secondary_id>
    <nct_id>NCT01715441</nct_id>
  </id_info>
  <brief_title>Sorafenib in Combination With Irinotecan in Metastatic Colorectal Cancer Patients With KRAS Mutated Tumors</brief_title>
  <acronym>NEXIRI2</acronym>
  <official_title>A Randomized Phase II Trial Assessing Sorafenib in Combination With Irinotecan in Metastatic Colorectal Cancer Patients With KRAS Mutated Tumors After Failure of All Drugs Known to be Effective</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut du Cancer de Montpellier - Val d'Aurelle</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institut du Cancer de Montpellier - Val d'Aurelle</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this multicenter randomized phase II trial is to determine the efficacy of&#xD;
      sorafenib and irinotecan combination versus irinotecan monotherapy or versus sorafenib&#xD;
      monotherapy in metastatic colorectal cancer patients with KRAS mutated tumors after failure&#xD;
      of all active drugs known to be effective.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2012</start_date>
  <completion_date type="Actual">September 2015</completion_date>
  <primary_completion_date type="Actual">March 2015</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Non-progression rate</measure>
    <time_frame>At 2 months</time_frame>
    <description>To evaluate the non-progression rate at 2 months according to RECIST criteria (Version 1.1)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease control rate</measure>
    <time_frame>At 2 months</time_frame>
    <description>According to RECIST criteria (Version 1.1)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment-related toxicity</measure>
    <time_frame>At 6 months</time_frame>
    <description>According to NCI CTC V4.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>At 6 months</time_frame>
    <description>Overall survival is defined as the time from the date of inclusion to the date of death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life questionnaire</measure>
    <time_frame>6 months</time_frame>
    <description>Using the EORTC QLQ-C30 questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>At 6 months</time_frame>
    <description>Progression Free Survival is defined as the time from the date of inclusion to first documentation of objective tumor progression or to death due to progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response rate</measure>
    <time_frame>At 2 months</time_frame>
    <description>According to RECIST criteria (Version 1.1)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Cmax and Tmax of sorafenib and irinotecan</measure>
    <time_frame>Up to 3 months</time_frame>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">173</enrollment>
  <condition>Metastatic Colorectal Cancer Patients With KRAS Mutated Tumors</condition>
  <arm_group>
    <arm_group_label>Irinotecan monotherapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intravenous infusion irinotecan 180 mg/m2 over 90 minutes (D1=D15) with cross over to irinotecan and sorafenib combination at progression.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sorafenib monotherapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Oral sorafenib 400 mg twice daily (total dose 800 mg/day) with cross over to irinotecan and sorafenib combination at progression</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sorafenib and irinotecan combination</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intravenous infusion irinotecan 120 mg/m2 over 90 minutes (D1=D15) at Cycle 1, 150 mg/m² at C2 if no diarrhea &gt; grade 1 and no other toxicity &gt; grade 2, and 180 mg/m² at C3 in the same conditions&#xD;
Oral sorafenib 400 mg twice daily (total dose 800 mg/day) from C1. 1 cycle = 15 days and 1 course = 4 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sorafenib and irinotecan combination</intervention_name>
    <arm_group_label>Sorafenib and irinotecan combination</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sorafenib monotherapy</intervention_name>
    <arm_group_label>Sorafenib monotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Irinotecan monotherapy</intervention_name>
    <arm_group_label>Irinotecan monotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female ≥ 18 years old&#xD;
&#xD;
          -  Histologically confirmed diagnosis of colorectal cancer&#xD;
&#xD;
          -  Asymptomatic or resected primary tumor&#xD;
&#xD;
          -  Metastatic colorectal cancer patient not eligible for curative surgery&#xD;
&#xD;
          -  At least one target lesion:&#xD;
&#xD;
               -  Unidimensionally measurable on cross-sectional imaging&#xD;
&#xD;
               -  In an area not previously irradiated&#xD;
&#xD;
          -  Disease progression after failure of active drugs (5-Fu or 5-Fu prodrugs, irinotecan,&#xD;
             oxaliplatin, bevacizumab)&#xD;
&#xD;
          -  Patients with bone metastases are eligible if they have other measurable lesions&#xD;
&#xD;
          -  WHO performance status ≤ 2&#xD;
&#xD;
          -  Confirmation of KRAS mutation in codons 12 or 13 in the primary tumor or metastases&#xD;
&#xD;
          -  Total bilirubin ≤ 1.5 ULN, ALT or AST ≤ 2.5 ULN (or &lt; 5 in case of liver impairment)&#xD;
&#xD;
          -  Haemoglobin ≥ 10 g/dL, neutrophils ≥ 1,500/mm3, platelets ≥ 100,000/mm3&#xD;
&#xD;
          -  Serum creatinine ≤ 1.5 ULN&#xD;
&#xD;
          -  Negative pregnancy test in women of childbearing potential&#xD;
&#xD;
          -  Use of an effective contraceptive method during the whole treatment and up to 3 months&#xD;
             after the completion of treatment in males and females&#xD;
&#xD;
          -  Life expectancy of at least 3 months&#xD;
&#xD;
          -  Informed consent signed prior any study specific procedures&#xD;
&#xD;
          -  Tumor evaluation should be performed within 3 weeks prior to starting treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of Gilbert's syndrome&#xD;
&#xD;
          -  Symptomatic brain metastases or carcinomatous meningitis&#xD;
&#xD;
          -  Bone-only metastases&#xD;
&#xD;
          -  History or presence of other cancers within the past 5 years (except curatively&#xD;
             treated non-melanoma skin cancer and in situ cervical cancer)&#xD;
&#xD;
          -  Prior surgery or radiotherapy within 4 weeks before entering the study&#xD;
&#xD;
          -  Cardiac arrhythmia requiring treatment (except for beta-blockers and digoxin),&#xD;
             unstable cardiac disease, myocardial infarction within the previous 6 months, &gt; grade&#xD;
             II NYHA heart failure, uncontrolled hypertension&#xD;
&#xD;
          -  Kalemia lower than normal serum potassium value&#xD;
&#xD;
          -  From ECG, QTc interval &gt; 470 ms&#xD;
&#xD;
          -  History of acute or chronic pancreatitis&#xD;
&#xD;
          -  History of epileptic seizures requiring long-term anticonvulsant therapy&#xD;
&#xD;
          -  History of organ transplantation with use of immunosuppression therapy&#xD;
&#xD;
          -  Severe bacterial or fungal infection (Grade &gt; 2 NCI-CTCAE v.4.0)&#xD;
&#xD;
          -  Known HIV infection&#xD;
&#xD;
          -  Long-term use of CYP 3A4 enzyme-inducing agents such as rifampicin, St. John's Wort&#xD;
             (hypericum perforatum), phenytoin, carbamazepine, phenobarbital, dexamethasone, and&#xD;
             ketoconazole&#xD;
&#xD;
          -  Pregnant or breastfeeding women&#xD;
&#xD;
          -  Bowel malabsorption or extended bowel resection that could affect the absorption of&#xD;
             sorafenib, occlusive syndrome, inability to take oral medications&#xD;
&#xD;
          -  Inflammatory bowel disease with chronic diarrhea (NCI-CTCAE v.4.0)&#xD;
&#xD;
          -  Participation in another clinical trial 30 days prior to study entry&#xD;
&#xD;
          -  Concurrent treatment with any other investigational product or anticancer therapy&#xD;
             (except for irinotecan or sorafenib)&#xD;
&#xD;
          -  Psychological, social, geographical disorders or any other condition that would&#xD;
             preclude study compliance (treatment administration and study follow-up).&#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>Emmanuelle SAMALIN, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>CRLC Val d'Aurelle-Paul Lamarque</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Marc YCHOU, MD,</last_name>
    <role>Study Chair</role>
    <affiliation>CRLC Val d'Aurelle</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hôpital AVICENNE</name>
      <address>
        <city>Bobigny</city>
        <zip>93009</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre François Baclesse</name>
      <address>
        <city>Caen</city>
        <zip>14076</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Oscar Lambret</name>
      <address>
        <city>Lille</city>
        <zip>59020</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Léon Bérard</name>
      <address>
        <city>Lyon</city>
        <zip>69373</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital LA TIMONE</name>
      <address>
        <city>Marseille</city>
        <zip>13365</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CRLC Val d'Aurelle-Paul Lamarque</name>
      <address>
        <city>Montpellier</city>
        <zip>34298</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>C.H.U. de REIMS</name>
      <address>
        <city>Reims</city>
        <zip>51092</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Charles Nicolle</name>
      <address>
        <city>Rouen</city>
        <zip>76038</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut de Cancérologie de l'Ouest - René Gauducheau</name>
      <address>
        <city>St. Herblain</city>
        <zip>44805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>March 2015</verification_date>
  <study_first_submitted>October 19, 2012</study_first_submitted>
  <study_first_submitted_qc>October 24, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 29, 2012</study_first_posted>
  <last_update_submitted>August 20, 2019</last_update_submitted>
  <last_update_submitted_qc>August 20, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 22, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Metastatic colorectal cancer patients</keyword>
  <keyword>KRAS mutation</keyword>
  <keyword>Sorafenib</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>Irinotecan</mesh_term>
    <mesh_term>Sorafenib</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/NCT01715441
org study id: NEXIRI2
secondary id: 2012-000644-94
nct id: NCT01715441
lead sponsor: 
has dmc: Yes
The aim of this multicenter randomized phase II trial is to determine the efficacy of
      sorafenib and irinotecan combination versus irinotecan monotherapy or versus sorafenib
      monotherapy in metastatic colorectal cancer patients with KRAS mutated tumors after failure
      of all active drugs known to be effective.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Non-progression rate
time frame: At 2 months
description: To evaluate the non-progression rate at 2 months according to RECIST criteria (Version 1.1)
measure: Disease control rate
time frame: At 2 months
description: According to RECIST criteria (Version 1.1)
measure: Treatment-related toxicity
time frame: At 6 months
description: According to NCI CTC V4.0
measure: Overall survival
time frame: At 6 months
description: Overall survival is defined as the time from the date of inclusion to the date of death from any cause.
measure: Quality of life questionnaire
time frame: 6 months
description: Using the EORTC QLQ-C30 questionnaire
measure: Progression Free Survival
time frame: At 6 months
description: Progression Free Survival is defined as the time from the date of inclusion to first documentation of objective tumor progression or to death due to progression.
measure: Response rate
time frame: At 2 months
description: According to RECIST criteria (Version 1.1)
measure: Cmax and Tmax of sorafenib and irinotecan
time frame: Up to 3 months
arm group label: Irinotecan monotherapy
arm group type: Active Comparator
description: Intravenous infusion irinotecan 180 mg/m2 over 90 minutes (D1=D15) with cross over to irinotecan and sorafenib combination at progression.
arm group label: Sorafenib monotherapy
arm group type: Active Comparator
description: Oral sorafenib 400 mg twice daily (total dose 800 mg/day) with cross over to irinotecan and sorafenib combination at progression
arm group label: Sorafenib and irinotecan combination
arm group type: Experimental
description: Intravenous infusion irinotecan 120 mg/m2 over 90 minutes (D1=D15) at Cycle 1, 150 mg/m² at C2 if no diarrhea > grade 1 and no other toxicity > grade 2, and 180 mg/m² at C3 in the same conditions
Oral sorafenib 400 mg twice daily (total dose 800 mg/day) from C1. 1 cycle = 15 days and 1 course = 4 weeks.
intervention type: Drug
intervention name: Sorafenib and irinotecan combination
arm group label: Sorafenib and irinotecan combination
intervention type: Drug
intervention name: Sorafenib monotherapy
arm group label: Sorafenib monotherapy
intervention type: Drug
intervention name: Irinotecan monotherapy
arm group label: Irinotecan monotherapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Emmanuelle SAMALIN, MD
role: Principal Investigator
affiliation: CRLC Val d'Aurelle-Paul Lamarque
last name: Marc YCHOU, MD,
role: Study Chair
affiliation: CRLC Val d'Aurelle
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Irinotecan
mesh term: Sorafenib