<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/NCT03280407</url>
  </required_header>
  <id_info>
    <org_study_id>S-20160158</org_study_id>
    <nct_id>NCT03280407</nct_id>
  </id_info>
  <brief_title>NEOadjuvant Chemotherapy Only Compared With Standard Treatment for Locally Advanced Rectal Cancer</brief_title>
  <acronym>NEOLAR</acronym>
  <official_title>NEOadjuvant Chemotherapy Only Compared With Standard Treatment for Locally Advanced Rectal Cancer: a Randomized Phase II Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zealand University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Zealand University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main clinical hypothesis is that compared to radio-chemotherapy for low and mid rectal&#xD;
      tumors or surgery for high rectal tumors neoadjuvant chemotherapy reduces the rate of distant&#xD;
      relapse without increasing the rate of local relapse.&#xD;
&#xD;
      The aim of the present study is to compare long term and short term outcomes in rectal cancer&#xD;
      patients undergoing standard treatment (radio-chemotherapy/surgery) or experimental&#xD;
      neoadjuvant chemotherapy/surgery Furthermore, early surgical and medical complications, the&#xD;
      functional outcome, toxicity and quality of life (QoL) may be improved if radiotherapy can be&#xD;
      avoided.&#xD;
&#xD;
      Exploratory analyses are planned in order to find potential predictive markers for selecting&#xD;
      patients to either radio-chemotherapy/surgery or neoadjuvant combination&#xD;
      chemotherapy/surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The standard treatment of locally advanced but resectable cancer in the middle or lower&#xD;
      rectum is preoperative radio-chemotherapy and in the upper part initial surgery. The clinical&#xD;
      benefit from radio-chemotherapy is primarily through a reduction in local relapse but the&#xD;
      treatment is associated with acute toxicity and long term functional dysfunction.&#xD;
      Subsequently, it is important to select patients with high risk of local relapse. Intense&#xD;
      systemic combination chemotherapy reduces the risk of distant relapse and increases survival&#xD;
      in the postoperative setting. The biological rationale is eradication of micrometastases and&#xD;
      hence it may be anticipated that earlier, i.e. neoadjuvant, combination therapy may improve&#xD;
      systemic control.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 1, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2018</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>
    <intervention_model_description>This is an open label, randomized phase II screening trial allocating eligible patients to either standard treatment for rectal cancer or experimental preoperative combination chemotherapy.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Disease free survival</measure>
    <time_frame>5 years</time_frame>
    <description>All patients will be evaluated with CT and MRI scans and clinically every 6 months for 2 years and annually until the number of events is reached and the trial is stopped (max 5 years)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>5 years</time_frame>
    <description>All patients will be evaluated with CT and MRI scans and clinically every 6 months for 2 years and annually for maximum 5 years</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Local relapse</measure>
    <time_frame>5 years</time_frame>
    <description>Defined to be within the pelvis. Any relapse should be verified by biopsy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Distant relapse</measure>
    <time_frame>5 years</time_frame>
    <description>Defined to be outside the pelvis. Any relapse should be verified by biopsy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Early toxicity</measure>
    <time_frame>5 years</time_frame>
    <description>Evaluated using CTCEA (Common Terminology Criteria for Adverse Events) version 4.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Late toxicity</measure>
    <time_frame>5 years</time_frame>
    <description>Evaluated using CTCEA version 4.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional outcome</measure>
    <time_frame>5 years</time_frame>
    <description>Measured with LARS questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life (QoL)</measure>
    <time_frame>5 years</time_frame>
    <description>Measured with EORTC QoL questionnaire</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">124</enrollment>
  <condition>Colorectal Neoplasm</condition>
  <condition>Colorectal Cancer</condition>
  <condition>Rectal Neoplasms</condition>
  <condition>Chemotherapy Effect</condition>
  <condition>Intestinal Disease</condition>
  <condition>Intestinal Neoplasms</condition>
  <condition>Rectal Cancer</condition>
  <arm_group>
    <arm_group_label>A, capecitabine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Radiochemotherapy with 50.4 Gy in 28 fractions concomitantly with chemotherapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B, FOLFOX or CAPOX</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Neoadjuvant chemotherapy with CAPOX (oxaliplatin/capecitabine) or FOLFOX regimen (oxaliplatin/leucovorin/5FU), according to institutional practice</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine</intervention_name>
    <description>Radio-chemotherapy with 50.4 Gy in 28 fractions to tumor and regional lymph nodes concomitantly with capecitabine 825 mg/m2 b.i.d</description>
    <arm_group_label>A, capecitabine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FOLFOX regimen (oxaliplatin/leucovorin/5FU)</intervention_name>
    <description>Six cycles: Oxaliplatin 85 mg/m2 day 1, leucovorin 400 mg/m2 day 1, 5FU 400 mg/m2 bolus day 1 and 5FU 2400 mg/ m2 over 46-48 hours day 1-3, repeated every two weeks.</description>
    <arm_group_label>B, FOLFOX or CAPOX</arm_group_label>
    <other_name>FOLFOX (oxaliplatin/leucovorin/5FU)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CAPOX (oxaliplatin/capecitabine)</intervention_name>
    <description>Four cycles: Oxaliplatin 130 mg/m2 day 1 and capecitabine 1000 mg/m2 b.i.d. days 1-14, repeated every 3 weeks.</description>
    <arm_group_label>B, FOLFOX or CAPOX</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adenocarcinoma of the rectum with the lower boarder within 15 cm from the anal verge&#xD;
&#xD;
          -  Locally advanced tumor based on imaging&#xD;
&#xD;
          -  T3 tumors within 10 cm from the anal verge fulfilling the criteria for preoperative&#xD;
             radio-chemotherapy according to Danish Colorectal Cancer Group (DCCG) guidelines&#xD;
&#xD;
          -  T3c or T4 tumors 10-15 cm from the anal verge&#xD;
&#xD;
          -  Deemed resectable at the multidisciplinary team (MDT) conference&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2&#xD;
&#xD;
          -  Age at least 18 years&#xD;
&#xD;
          -  Adequate bone marrow, liver and renal function allowing systemic chemotherapy&#xD;
&#xD;
          -  Absolute neutrophil count ≥1.5x109/l and thrombocytes ≥ 100x109/l.&#xD;
&#xD;
          -  Bilirubin ≤ 1.5 x upper normal value and alanine aminotransferase ≤ 3 x upper normal&#xD;
             value&#xD;
&#xD;
          -  Calculated or measured renal glomerular filtration rate at least 30 mL/min&#xD;
&#xD;
          -  Anticonception for fertile women and for male patients with a fertile partner.&#xD;
             Intrauterine device, vasectomy of a female subject's male partner or hormonal&#xD;
             contraceptive are acceptable&#xD;
&#xD;
          -  Written and orally informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Distant metastasis&#xD;
&#xD;
          -  Invasive ingrowth into other organs&#xD;
&#xD;
          -  Incapacity, frailty, disability and comorbidity to a degree that according to the&#xD;
             investigator is not compatible with combination chemotherapy&#xD;
&#xD;
          -  Previous radiotherapy to the pelvis&#xD;
&#xD;
          -  Previous treatment with 5FU or oxaliplatin&#xD;
&#xD;
          -  Surgery within two weeks&#xD;
&#xD;
          -  Neuropathy NCI grade &gt; 1&#xD;
&#xD;
          -  Other malignant tumor within 5 years except non-melanoma skin cancer or carcinoma in&#xD;
             situ cervicis uteri&#xD;
&#xD;
          -  Pregnant (positive pregnancy test) or breast feeding women&#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>Ismail Gögenur, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Department of Surgery, ZUH</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Lars Henrik Jensen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vejle Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ismail Gögenur, MD</last_name>
    <phone>+45 26336426</phone>
    <email>igo@regionsjaelland.dk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Lars Henrik Jensen, MD</last_name>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Vejle Hospital</name>
      <address>
        <city>Vejle</city>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lars Henrik Jensen, MD PhD</last_name>
      <email>lars.henrik.jensen@rsyd.dk</email>
    </contact>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 7, 2017</study_first_submitted>
  <study_first_submitted_qc>September 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <last_update_submitted>September 26, 2017</last_update_submitted>
  <last_update_submitted_qc>September 26, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Zealand University Hospital</investigator_affiliation>
    <investigator_full_name>Ismail Gögenur</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Neoadjuvant chemotherapy,</keyword>
  <keyword>locally advanced rectal cancer,</keyword>
  <keyword>chemotherapy</keyword>
  <keyword>CAPOX (oxaliplatin/capecitabine)</keyword>
  <keyword>FOLFOX (oxaliplatin/leucovorin/5FU)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Colorectal Neoplasms</mesh_term>
    <mesh_term>Rectal Neoplasms</mesh_term>
    <mesh_term>Intestinal Neoplasms</mesh_term>
    <mesh_term>Intestinal Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leucovorin</mesh_term>
    <mesh_term>Capecitabine</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
    <mesh_term>Levoleucovorin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Undecided</ipd_description>
  </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/NCT03280407
org study id: S-20160158
nct id: NCT03280407
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The main clinical hypothesis is that compared to radio-chemotherapy for low and mid rectal
      tumors or surgery for high rectal tumors neoadjuvant chemotherapy reduces the rate of distant
      relapse without increasing the rate of local relapse.

      The aim of the present study is to compare long term and short term outcomes in rectal cancer
      patients undergoing standard treatment (radio-chemotherapy/surgery) or experimental
      neoadjuvant chemotherapy/surgery Furthermore, early surgical and medical complications, the
      functional outcome, toxicity and quality of life (QoL) may be improved if radiotherapy can be
      avoided.

      Exploratory analyses are planned in order to find potential predictive markers for selecting
      patients to either radio-chemotherapy/surgery or neoadjuvant combination
      chemotherapy/surgery.
The standard treatment of locally advanced but resectable cancer in the middle or lower
      rectum is preoperative radio-chemotherapy and in the upper part initial surgery. The clinical
      benefit from radio-chemotherapy is primarily through a reduction in local relapse but the
      treatment is associated with acute toxicity and long term functional dysfunction.
      Subsequently, it is important to select patients with high risk of local relapse. Intense
      systemic combination chemotherapy reduces the risk of distant relapse and increases survival
      in the postoperative setting. The biological rationale is eradication of micrometastases and
      hence it may be anticipated that earlier, i.e. neoadjuvant, combination therapy may improve
      systemic control.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is an open label, randomized phase II screening trial allocating eligible patients to either standard treatment for rectal cancer or experimental preoperative combination chemotherapy.
primary purpose: Treatment
masking: None (Open Label)
measure: Disease free survival
time frame: 5 years
description: All patients will be evaluated with CT and MRI scans and clinically every 6 months for 2 years and annually until the number of events is reached and the trial is stopped (max 5 years)
measure: Overall survival
time frame: 5 years
description: All patients will be evaluated with CT and MRI scans and clinically every 6 months for 2 years and annually for maximum 5 years
measure: Local relapse
time frame: 5 years
description: Defined to be within the pelvis. Any relapse should be verified by biopsy
measure: Distant relapse
time frame: 5 years
description: Defined to be outside the pelvis. Any relapse should be verified by biopsy
measure: Early toxicity
time frame: 5 years
description: Evaluated using CTCEA (Common Terminology Criteria for Adverse Events) version 4.
measure: Late toxicity
time frame: 5 years
description: Evaluated using CTCEA version 4.
measure: Functional outcome
time frame: 5 years
description: Measured with LARS questionnaire
measure: Quality of life (QoL)
time frame: 5 years
description: Measured with EORTC QoL questionnaire
arm group label: A, capecitabine
arm group type: Active Comparator
description: Radiochemotherapy with 50.4 Gy in 28 fractions concomitantly with chemotherapy
arm group label: B, FOLFOX or CAPOX
arm group type: Experimental
description: Neoadjuvant chemotherapy with CAPOX (oxaliplatin/capecitabine) or FOLFOX regimen (oxaliplatin/leucovorin/5FU), according to institutional practice
intervention type: Drug
intervention name: Capecitabine
description: Radio-chemotherapy with 50.4 Gy in 28 fractions to tumor and regional lymph nodes concomitantly with capecitabine 825 mg/m2 b.i.d
arm group label: A, capecitabine
intervention type: Drug
intervention name: FOLFOX regimen (oxaliplatin/leucovorin/5FU)
description: Six cycles: Oxaliplatin 85 mg/m2 day 1, leucovorin 400 mg/m2 day 1, 5FU 400 mg/m2 bolus day 1 and 5FU 2400 mg/ m2 over 46-48 hours day 1-3, repeated every two weeks.
arm group label: B, FOLFOX or CAPOX
other name: FOLFOX (oxaliplatin/leucovorin/5FU)
intervention type: Drug
intervention name: CAPOX (oxaliplatin/capecitabine)
description: Four cycles: Oxaliplatin 130 mg/m2 day 1 and capecitabine 1000 mg/m2 b.i.d. days 1-14, repeated every 3 weeks.
arm group label: B, FOLFOX or CAPOX
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ismail Gögenur, MD
role: Study Chair
affiliation: Department of Surgery, ZUH
last name: Lars Henrik Jensen, MD
role: Principal Investigator
affiliation: Vejle Hospital
last name: Ismail Gögenur, MD
phone: +45 26336426
email: igo@regionsjaelland.dk
last name: Lars Henrik Jensen, MD
facility: 
status: Recruiting
contact: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: Zealand University Hospital
investigator full name: Ismail Gögenur
investigator title: Professor
mesh term: Neoplasms
mesh term: Colorectal Neoplasms
mesh term: Rectal Neoplasms
mesh term: Intestinal Neoplasms
mesh term: Intestinal Diseases
mesh term: Leucovorin
mesh term: Capecitabine
mesh term: Oxaliplatin
mesh term: Levoleucovorin
sharing ipd: Undecided
ipd description: Undecided