<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/NCT01718808</url>
  </required_header>
  <id_info>
    <org_study_id>SAKK 41/10</org_study_id>
    <nct_id>NCT01718808</nct_id>
  </id_info>
  <brief_title>Cetuximab for Elderly Patients With mCRC</brief_title>
  <official_title>Cetuximab Monotherapy and Cetuximab Plus Capecitabine as First-line Treatment in Elderly Patients With KRAS- and BRAF Wild-type Metastatic Colorectal Cancer. A Multicenter Phase II Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Swiss Group for Clinical Cancer Research</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Swiss Group for Clinical Cancer Research</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      OBJECTIVE: The objective of the trial is to judge on the benefit obtained by an upfront&#xD;
      cetuximab treatment delivered as monotherapy or as part of a combination treatment with&#xD;
      capecitabine in vulnerable elderly patients selected for V-Ki-ras2 Kirsten rat sarcoma viral&#xD;
      oncogene homolog (KRAS) wild-type and B-type Raf kinase (BRAF) wild-type metastatic&#xD;
      colorectal cancer (mCRC).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary endpoint: If in a treatment arm the number of patients alive and without progression&#xD;
      at 12 weeks is 17 or more, this arm will be considered promising, otherwise not promising.&#xD;
      Additionally, a two-sided 95% confidence interval for the difference in Progression free&#xD;
      survival (PFS) rates between the two arms will be calculated.&#xD;
&#xD;
      Secondary endpoints and patient characteristics:&#xD;
&#xD;
        -  Laboratory values may be expressed as the absolute values (continuous variables) or/and&#xD;
           as grading (ordinal categorical variables).&#xD;
&#xD;
        -  Generally for each categorical variable the results will be summarized by frequencies&#xD;
           and percentages. For response rates 95% Clopper-Pearson confidence intervals will be&#xD;
           calculated.&#xD;
&#xD;
        -  For each adverse event, the results will be summarized by frequencies and percentages of&#xD;
           different grades among all cycles as well as by frequencies and percentages of the&#xD;
           within-patient worst grades&#xD;
&#xD;
        -  For each continuous variable the results will be summarized by descriptive statistics.&#xD;
&#xD;
        -  Time-to-event variables will be presented by Kaplan-Meier curves and summarized by&#xD;
           medians and 95% confidence intervals.&#xD;
&#xD;
        -  All analysis will be done by treatment arm.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    FU for 3 years from randomization as initially planned is stopped as we do not expect any&#xD;
    changes to the endpoints in the future after one year of FU.&#xD;
  </why_stopped>
  <start_date type="Actual">November 2012</start_date>
  <completion_date type="Actual">January 2017</completion_date>
  <primary_completion_date type="Actual">December 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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression free survival in week 12</measure>
    <time_frame>in week 12</time_frame>
    <description>A progression event is defined as (whichever occurs first):&#xD;
Progressive disease (PD) assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1&#xD;
Death of any cause&#xD;
Starting of second line treatment&#xD;
No tumor assessment 85 days (+/- 7 days) after registration which shows stabilisation or response Patients without tumor assessment at week 12 but with a later assessment showing absence of progression without subsequent treatment will be counted as a progression free at week 12</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Quality of life (QL)</measure>
    <time_frame>Baseline, in week 7, 13 and 19</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events (CTCAE v 4.0)</measure>
    <time_frame>Adverse events are assessed by Common terminology criteria for adverse events (CTCAE) v4.0. From randomization until 30 days after end of treatment (estimated up to 2 years).</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response (OR)</measure>
    <time_frame>Before start of treatment. In week 13 and every 12 weeks up to 2 years.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>PFS will be calculated sustained from randomization until documented PD or death, whichever occurs first (estimated up to 2 years).</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Overall survival will be calculated from randomization until death (estimated up to 2 years).</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall treatment utility (OTU) (predefined composite endpoint including clinical benefit, tolerability and acceptability of the treatment)</measure>
    <time_frame>Until week 19.</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Metastatic Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>Arm A: Cetuximab</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cetuximab 500 mg/m2 every 2 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B: Cetuximab and Capecitabine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cetuximab 500 mg/m2 every 2 weeks plus Capecitabine 1000 mg/m2 (*) bid d1-14 every 3 weeks&#xD;
* 750 mg/m2 if creatinine-clearance 30-50 ml/min</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cetuximab</intervention_name>
    <description>Cetuximab 500 mg/m2 every second week (days 1, 15, 29, etc.) until progression or unacceptable toxicity</description>
    <arm_group_label>Arm A: Cetuximab</arm_group_label>
    <arm_group_label>Arm B: Cetuximab and Capecitabine</arm_group_label>
    <other_name>Erbitux</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine</intervention_name>
    <description>Capecitabine 1000 mg/m2 bid p.o. (750 mg/m2 if creatinine clearance 30-50 ml/min according to Cockroft-Gault formula, on days 1-14 every 3 weeks, restart on day 22</description>
    <arm_group_label>Arm B: Cetuximab and Capecitabine</arm_group_label>
    <other_name>Xeloda</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient has given written informed consent before any trial specific treatment&#xD;
&#xD;
          -  Histological proven diagnosis of colorectal cancer, metastatic or inoperable advanced,&#xD;
             not amenable to curative therapy&#xD;
&#xD;
          -  Measurable disease, defined as at least one lesion (outside of irradiated areas) that&#xD;
             can be measured in at least one dimension as ≥ 10 mm (≥ 15 mm in case of lymph nodes)&#xD;
             according to RECIST v1.1&#xD;
&#xD;
          -  Tumour with wild-type KRAS and wild-type BRAF gene&#xD;
&#xD;
          -  No previous systemic chemotherapy for metastatic disease (previous adjuvant&#xD;
             chemotherapy is allowed if completed &gt;6 months before randomization, previous rectal&#xD;
             radio-chemo therapy if completed &gt;1 month before randomization)&#xD;
&#xD;
          -  WHO performance status 0 or 1&#xD;
&#xD;
          -  Age &gt;75 years; or: age ≥ 70 years with at least one of the following factors:&#xD;
&#xD;
          -  Any functional dependence as measured by Instrumental Activities of Daily Life (IADL).&#xD;
             Significant comorbidity according to the Cumulative Illness Rating Scale for geriatric&#xD;
             patients (CIRS-G; any severe comorbidity &gt; grade 3 or a total score &gt; 5 qualifies)&#xD;
&#xD;
          -  Neutrophils ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L&#xD;
&#xD;
          -  Bilirubin ≤ 2.0 x Upper Limit of Normal (ULN) (unless known Gilbert-Meulengracht&#xD;
             syndrome), aspartate aminotransferase (AST)&lt;2.5xULN&#xD;
&#xD;
          -  Calculated creatinine clearance ≥ 30 ml/min. (according to the formula of&#xD;
             Cockcroft-Gault)&#xD;
&#xD;
          -  Patient is able to swallow oral medication&#xD;
&#xD;
          -  Baseline Quality of Life forms have been completed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Documented or suspected cerebral and/or leptomeningeal metastases (no cerebral&#xD;
             baseline imaging required in asymptomatic patients)&#xD;
&#xD;
          -  Risk of rapid deterioration due to tumor symptoms or tumor complications&#xD;
&#xD;
          -  Synchronous or prior malignancy other than adequately treated non-melanomatous skin&#xD;
             cancer or in situ carcinoma of the cervix, other malignancies unless disease free &gt; 2&#xD;
             years&#xD;
&#xD;
          -  Prior anti-EGFR (Epidermal Growth Factor Receptor) antibody therapy&#xD;
&#xD;
          -  Severe or uncontrolled cardiovascular disease (e.g. acute coronary syndromes, cardiac&#xD;
             failure NYHA (New York Heart Association) III or IV, clinically relevant myopathy,&#xD;
             history of myocardial infarction within the last 12 months, significant arrhythmias)&#xD;
&#xD;
          -  Concurrent severe uncontrolled medical illness (judged by the investigator) which&#xD;
             could impair the ability of the patient to participate in the trial (e.g. uncontrolled&#xD;
             infection, uncontrolled diabetes mellitus, active autoimmune disease)&#xD;
&#xD;
          -  Known dihydropyrimidine dehydrogenase (DPD) deficiency&#xD;
&#xD;
          -  Known hypersensitivity to trial drugs or hypersensitivity to any other component of&#xD;
             the trial drug&#xD;
&#xD;
          -  Definite contraindications for the use of corticosteroids or antihistamines as&#xD;
             premedication&#xD;
&#xD;
          -  Lack of physical integrity of the upper gastrointestinal tract or malabsorption&#xD;
             syndrome or history of inflammatory intestinal disease, or other disease which could&#xD;
             alter drug absorption&#xD;
&#xD;
          -  Psychiatric disorder precluding understanding of information on trial related topics,&#xD;
             giving informed consent, filling out QL forms, or interfering with compliance with&#xD;
             oral drug intake&#xD;
&#xD;
          -  Any concomitant drugs contraindicated for use with the trial drugs according to the&#xD;
             Swissmedic approved product information&#xD;
&#xD;
          -  Concurrent treatment with other experimental drugs or other anti-cancer therapy and/or&#xD;
             treatment in a clinical trial within 30 days prior to randomization&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>70 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dirk Kienle, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Kantonsspital Graubünden</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Roger von Moos, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Kantonsspital Graubünden</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ralph Winterhalder, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Luzerner Kantonsspital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Dieter Köberle, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Cantonal Hospital of St. Gallen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Universitaetsspital-Basel</name>
      <address>
        <city>Basel</city>
        <zip>CH-4031</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inselspital, Bern</name>
      <address>
        <city>Bern</city>
        <zip>CH-3010</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spitalzentrum Biel</name>
      <address>
        <city>Biel</city>
        <zip>CH-2501</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Fribourgeois</name>
      <address>
        <city>Fribourg</city>
        <zip>1708</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Cantonal Universitaire de Geneve</name>
      <address>
        <city>Geneva</city>
        <zip>CH-1211</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire Vaudois</name>
      <address>
        <city>Lausanne</city>
        <zip>CH-1011</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kantonsspital Luzern</name>
      <address>
        <city>Luzern</city>
        <zip>6000</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kantonsspital Muensterlingen</name>
      <address>
        <city>Muensterlingen</city>
        <zip>8596</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kantonsspital - St. Gallen</name>
      <address>
        <city>St. Gallen</city>
        <zip>CH-9007</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SpitalSTS AG Simmental-Thun-Saanenland</name>
      <address>
        <city>Thun</city>
        <zip>3600</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kantonsspital Winterthur</name>
      <address>
        <city>Winterthur</city>
        <zip>CH-8400</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinik Hirslanden</name>
      <address>
        <city>Zurich</city>
        <zip>CH-8032</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UniversitaetsSpital Zuerich</name>
      <address>
        <city>Zurich</city>
        <zip>CH-8091</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stadtspital Triemli</name>
      <address>
        <city>Zürich</city>
        <zip>8063</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>October 22, 2012</study_first_submitted>
  <study_first_submitted_qc>October 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 31, 2012</study_first_posted>
  <last_update_submitted>January 23, 2017</last_update_submitted>
  <last_update_submitted_qc>January 23, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 24, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Metastatic Colorectal Cancer</keyword>
  <keyword>KRAS</keyword>
  <keyword>BRAF</keyword>
  <keyword>Wild-type Metastatic</keyword>
  <keyword>Cetuximab</keyword>
  <keyword>Capecitabine</keyword>
  <keyword>Phase II Trial</keyword>
  <keyword>Elderly Patients</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>Capecitabine</mesh_term>
    <mesh_term>Cetuximab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT01718808
org study id: SAKK 41/10
nct id: NCT01718808
lead sponsor: 
has dmc: No
OBJECTIVE: The objective of the trial is to judge on the benefit obtained by an upfront
      cetuximab treatment delivered as monotherapy or as part of a combination treatment with
      capecitabine in vulnerable elderly patients selected for V-Ki-ras2 Kirsten rat sarcoma viral
      oncogene homolog (KRAS) wild-type and B-type Raf kinase (BRAF) wild-type metastatic
      colorectal cancer (mCRC).
Primary endpoint: If in a treatment arm the number of patients alive and without progression
      at 12 weeks is 17 or more, this arm will be considered promising, otherwise not promising.
      Additionally, a two-sided 95% confidence interval for the difference in Progression free
      survival (PFS) rates between the two arms will be calculated.

      Secondary endpoints and patient characteristics:

        -  Laboratory values may be expressed as the absolute values (continuous variables) or/and
           as grading (ordinal categorical variables).

        -  Generally for each categorical variable the results will be summarized by frequencies
           and percentages. For response rates 95% Clopper-Pearson confidence intervals will be
           calculated.

        -  For each adverse event, the results will be summarized by frequencies and percentages of
           different grades among all cycles as well as by frequencies and percentages of the
           within-patient worst grades

        -  For each continuous variable the results will be summarized by descriptive statistics.

        -  Time-to-event variables will be presented by Kaplan-Meier curves and summarized by
           medians and 95% confidence intervals.

        -  All analysis will be done by treatment arm.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression free survival in week 12
time frame: in week 12
description: A progression event is defined as (whichever occurs first):
Progressive disease (PD) assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Death of any cause
Starting of second line treatment
No tumor assessment 85 days (+/- 7 days) after registration which shows stabilisation or response Patients without tumor assessment at week 12 but with a later assessment showing absence of progression without subsequent treatment will be counted as a progression free at week 12
measure: Quality of life (QL)
time frame: Baseline, in week 7, 13 and 19
measure: Adverse events (CTCAE v 4.0)
time frame: Adverse events are assessed by Common terminology criteria for adverse events (CTCAE) v4.0. From randomization until 30 days after end of treatment (estimated up to 2 years).
measure: Overall Response (OR)
time frame: Before start of treatment. In week 13 and every 12 weeks up to 2 years.
measure: Progression free survival (PFS)
time frame: PFS will be calculated sustained from randomization until documented PD or death, whichever occurs first (estimated up to 2 years).
measure: Overall Survival (OS)
time frame: Overall survival will be calculated from randomization until death (estimated up to 2 years).
measure: Overall treatment utility (OTU) (predefined composite endpoint including clinical benefit, tolerability and acceptability of the treatment)
time frame: Until week 19.
arm group label: Arm A: Cetuximab
arm group type: Active Comparator
description: Cetuximab 500 mg/m2 every 2 weeks
arm group label: Arm B: Cetuximab and Capecitabine
arm group type: Active Comparator
description: Cetuximab 500 mg/m2 every 2 weeks plus Capecitabine 1000 mg/m2 (*) bid d1-14 every 3 weeks
* 750 mg/m2 if creatinine-clearance 30-50 ml/min
intervention type: Drug
intervention name: Cetuximab
description: Cetuximab 500 mg/m2 every second week (days 1, 15, 29, etc.) until progression or unacceptable toxicity
arm group label: Arm A: Cetuximab
arm group label: Arm B: Cetuximab and Capecitabine
other name: Erbitux
intervention type: Drug
intervention name: Capecitabine
description: Capecitabine 1000 mg/m2 bid p.o. (750 mg/m2 if creatinine clearance 30-50 ml/min according to Cockroft-Gault formula, on days 1-14 every 3 weeks, restart on day 22
arm group label: Arm B: Cetuximab and Capecitabine
other name: Xeloda
criteria: 
gender: All
minimum age: 70 Years
maximum age: N/A
healthy volunteers: No
last name: Dirk Kienle, MD
role: Study Chair
affiliation: Kantonsspital Graubünden
last name: Roger von Moos, MD
role: Study Chair
affiliation: Kantonsspital Graubünden
last name: Ralph Winterhalder, MD
role: Study Chair
affiliation: Luzerner Kantonsspital
last name: Dieter Köberle, MD
role: Study Chair
affiliation: Cantonal Hospital of St. Gallen
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Switzerland
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Capecitabine
mesh term: Cetuximab
sharing ipd: No