<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/NCT02978612</url>
  </required_header>
  <id_info>
    <org_study_id>2015/1252</org_study_id>
    <nct_id>NCT02978612</nct_id>
  </id_info>
  <brief_title>Adjuvant Chemotherapy In Elderly With Colon Cancer Stage III</brief_title>
  <acronym>ACE</acronym>
  <official_title>Adjuvant Chemotherapy In Elderly With Colon Cancer Stage III - Geriatric Assessment and Prognostic Gene Signatures</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Oslo University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Oslo University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase 2, randomized study where the aim of the study is to investigate the&#xD;
      tolerance of adjuvant chemotherapy, measured by functional decline, after surgery for colon&#xD;
      cancer stage III in elderly patients. Secondary aims are disease-free survival, toxicity,&#xD;
      late functional outcome, quality of life, to establish a geriatric assessment for selection&#xD;
      of patients, and to examine the prognostic value of gene signature tests / biomarkers for&#xD;
      stage III colon cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients ≥ 75 years who have undergone surgery for colon cancer stage III, are eligible for&#xD;
      inclusion in the study. Non-eligibility includes patients with obvious impaired cognitive or&#xD;
      physical function or patients living in nursing homes. After signing informed consent, the&#xD;
      patients first undergo geriatric assessment. Patients that are classified as having fit or&#xD;
      intermediate function, and with no significant cardiovascular disease, are randomized with a&#xD;
      2:1 randomization process to either chemotherapy (Arm A: Capecitabine 1000 mg/m2 bid day 1-14&#xD;
      q3 weeks, 8 cycles) or no chemotherapy (Arm B: observation).&#xD;
&#xD;
      The purpose of this study is to examine the tolerability of chemotherapy in elderly (&gt; 75&#xD;
      years) patients operated on for colon cancer stage III. There is little evidence of benefit&#xD;
      and tolerability of this therapy in the elderly; it is recommended individual consideration&#xD;
      in elderly. In the study, a comprehensive geriatric a comprehensive geriatric assessment is&#xD;
      performed first, to exclude frail patients or patients with serious comorbidities such as&#xD;
      cardiovascular disease. Fit or intermediate patients will then be randomized so that 2/3 will&#xD;
      receive chemotherapy with capecitabine tablets for 6 months, and 1/3 will not receive&#xD;
      chemotherapy. A new geriatric assessment is performed after 6 and 12 months. The main&#xD;
      objective of the study is to examine whether chemotherapy leads to significant loss of&#xD;
      function, but secondary aims include survival, quality of life, and prognostic effect of&#xD;
      biomarkers. The study may provide useful information on selection of patients who tolerate&#xD;
      and benefit from adjuvant chemotherapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>June 2016</start_date>
  <completion_date type="Anticipated">January 2032</completion_date>
  <primary_completion_date type="Actual">November 2022</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>Functional decline in instrumental activities of daily living (IADL) and/or activities of daily living (ADL)</measure>
    <time_frame>1 year after surgery</time_frame>
    <description>Tolerance of adjuvant chemotherapy in elderly patients, measured as functional decline or independency, by ADL and IADL questionnaires.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Relative dose intensity; i.e the percentage of planned chemotherapy dose the patient actually receives</measure>
    <time_frame>through study completion</time_frame>
    <description>Number of planned chemotherapy cycles given, total dose given</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity of chemotherapy</measure>
    <time_frame>During treatment and follow-up 1 year after surgery</time_frame>
    <description>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease-free survival</measure>
    <time_frame>3 years after surgery</time_frame>
    <description>Follow-up, 3-year disease-free survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life questionnaire 1</measure>
    <time_frame>Time of randomization, 6 months and 1 year after surgery</time_frame>
    <description>EQ-5D-5L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life questionnaire 2</measure>
    <time_frame>Time of randomization, 6 months and 1 year after surgery</time_frame>
    <description>EORTC QLQ-C30</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life questionnaire 3</measure>
    <time_frame>Time of randomization, 6 months and 1 year after surgery</time_frame>
    <description>QLQ-ELD14</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Validation of the performance of prognostic biomarkers in estimating disease-free survival</measure>
    <time_frame>3 years after surgery</time_frame>
    <description>Prognostic biomarkers validated for performance in estimating 3-year disease-free survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>5 years after surgery</time_frame>
    <description>Follow-up, 5-year disease-free survival</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">170</enrollment>
  <condition>Colon Cancer</condition>
  <arm_group>
    <arm_group_label>Arm Capecitabine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Capecitabine 1000 mg/m2 bid day 1-14 q3 weeks, 8 cycles</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm No treatment</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>no chemotherapy, observation</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine</intervention_name>
    <description>Capecitabine is a prodrug to 5-fluorouracil. It is used for adjuvant chemotherapy after surgery for colon cancer. The tablets are either 150 mg or 500 mg</description>
    <arm_group_label>Arm Capecitabine</arm_group_label>
    <other_name>Xeloda</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Radical surgery (R0/R1) for colon cancer&#xD;
&#xD;
          -  Histologically verified adenocarcinoma of the colon&#xD;
&#xD;
          -  Histologically verified lymph node metastases (Stage III)&#xD;
&#xD;
          -  Age ≥ 75 years&#xD;
&#xD;
          -  Able to undergo ambulatory treatment (adequate physical and mental function)&#xD;
&#xD;
          -  Signed informed consent and expected cooperation of the patients for the treatment and&#xD;
             follow up must be obtained and documented according to The International Conference on&#xD;
             Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human&#xD;
             Use (ICH GCP) and national regulations.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Distant metastases (stage IV)&#xD;
&#xD;
          -  Frail according to geriatric assessment&#xD;
&#xD;
          -  Significant cardiovascular disease (congestive heart failure, symptomatic coronary&#xD;
             artery disease and cardiac dysrhythmia) or myocardial infarction within the past 12&#xD;
             months&#xD;
&#xD;
          -  Previous treatment with chemotherapy for colorectal cancer&#xD;
&#xD;
          -  Metastatic disease from other cancer&#xD;
&#xD;
          -  Reduced cognitive function not enabling ability to give informed consent or compliance&#xD;
             with the study&#xD;
&#xD;
          -  History of prior or concurrent malignant neoplasm other than colorectal adenocarcinoma&#xD;
             within the past five years, except curatively treated non-melanoma skin cancer or in&#xD;
             situ carcinoma of the cervix&#xD;
&#xD;
          -  Adverse reactions or hypersensitivity to capecitabine or related drugs and/or its&#xD;
             excipients. Need to use medications contraindicated according to SmPC of the IMP(s),&#xD;
             such as sorivudine, brivudin or chemically related compounds. Any other&#xD;
             contraindication listed on the summary of product characteristics (SmPC) of the&#xD;
             investigational medicinal Product (IMP)&#xD;
&#xD;
          -  Use of methotrexate or other cytotoxic drugs as treatment of rheumatoid arthritis or&#xD;
             other inflammatory disease and where it is considered contraindicated to stop this&#xD;
             medication&#xD;
&#xD;
          -  Known dihydropyrimidine dehydrogenase (DPD) deficiency&#xD;
&#xD;
          -  Any reason why, in the opinion of the investigator, the patient should not participate&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>75 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marianne G Guren, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Oslo University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Oslo University Hospital</name>
      <address>
        <city>Oslo</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Norway</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>June 15, 2016</study_first_submitted>
  <study_first_submitted_qc>November 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 1, 2016</study_first_posted>
  <last_update_submitted>March 22, 2023</last_update_submitted>
  <last_update_submitted_qc>March 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Oslo University Hospital</investigator_affiliation>
    <investigator_full_name>Marianne Grønlie Guren</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Colorectal Neoplasms</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colonic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Capecitabine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02978612
org study id: 2015/1252
nct id: NCT02978612
lead sponsor: 
has dmc: No
This is a phase 2, randomized study where the aim of the study is to investigate the
      tolerance of adjuvant chemotherapy, measured by functional decline, after surgery for colon
      cancer stage III in elderly patients. Secondary aims are disease-free survival, toxicity,
      late functional outcome, quality of life, to establish a geriatric assessment for selection
      of patients, and to examine the prognostic value of gene signature tests / biomarkers for
      stage III colon cancer.
Patients ≥ 75 years who have undergone surgery for colon cancer stage III, are eligible for
      inclusion in the study. Non-eligibility includes patients with obvious impaired cognitive or
      physical function or patients living in nursing homes. After signing informed consent, the
      patients first undergo geriatric assessment. Patients that are classified as having fit or
      intermediate function, and with no significant cardiovascular disease, are randomized with a
      2:1 randomization process to either chemotherapy (Arm A: Capecitabine 1000 mg/m2 bid day 1-14
      q3 weeks, 8 cycles) or no chemotherapy (Arm B: observation).

      The purpose of this study is to examine the tolerability of chemotherapy in elderly (> 75
      years) patients operated on for colon cancer stage III. There is little evidence of benefit
      and tolerability of this therapy in the elderly; it is recommended individual consideration
      in elderly. In the study, a comprehensive geriatric a comprehensive geriatric assessment is
      performed first, to exclude frail patients or patients with serious comorbidities such as
      cardiovascular disease. Fit or intermediate patients will then be randomized so that 2/3 will
      receive chemotherapy with capecitabine tablets for 6 months, and 1/3 will not receive
      chemotherapy. A new geriatric assessment is performed after 6 and 12 months. The main
      objective of the study is to examine whether chemotherapy leads to significant loss of
      function, but secondary aims include survival, quality of life, and prognostic effect of
      biomarkers. The study may provide useful information on selection of patients who tolerate
      and benefit from adjuvant chemotherapy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Functional decline in instrumental activities of daily living (IADL) and/or activities of daily living (ADL)
time frame: 1 year after surgery
description: Tolerance of adjuvant chemotherapy in elderly patients, measured as functional decline or independency, by ADL and IADL questionnaires.
measure: Relative dose intensity; i.e the percentage of planned chemotherapy dose the patient actually receives
time frame: through study completion
description: Number of planned chemotherapy cycles given, total dose given
measure: Toxicity of chemotherapy
time frame: During treatment and follow-up 1 year after surgery
description: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
measure: Disease-free survival
time frame: 3 years after surgery
description: Follow-up, 3-year disease-free survival
measure: Quality of life questionnaire 1
time frame: Time of randomization, 6 months and 1 year after surgery
description: EQ-5D-5L
measure: Quality of life questionnaire 2
time frame: Time of randomization, 6 months and 1 year after surgery
description: EORTC QLQ-C30
measure: Quality of life questionnaire 3
time frame: Time of randomization, 6 months and 1 year after surgery
description: QLQ-ELD14
measure: Validation of the performance of prognostic biomarkers in estimating disease-free survival
time frame: 3 years after surgery
description: Prognostic biomarkers validated for performance in estimating 3-year disease-free survival
measure: Overall survival
time frame: 5 years after surgery
description: Follow-up, 5-year disease-free survival
arm group label: Arm Capecitabine
arm group type: Experimental
description: Capecitabine 1000 mg/m2 bid day 1-14 q3 weeks, 8 cycles
arm group label: Arm No treatment
arm group type: No Intervention
description: no chemotherapy, observation
intervention type: Drug
intervention name: Capecitabine
description: Capecitabine is a prodrug to 5-fluorouracil. It is used for adjuvant chemotherapy after surgery for colon cancer. The tablets are either 150 mg or 500 mg
arm group label: Arm Capecitabine
other name: Xeloda
criteria: 
gender: All
minimum age: 75 Years
maximum age: N/A
healthy volunteers: No
last name: Marianne G Guren, MD, PhD
role: Principal Investigator
affiliation: Oslo University Hospital
facility: 
country: Norway
responsible party type: Principal Investigator
investigator affiliation: Oslo University Hospital
investigator full name: Marianne Grønlie Guren
investigator title: MD, PhD
mesh term: Colonic Neoplasms
mesh term: Capecitabine
sharing ipd: Undecided