<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/NCT03259035</url>
  </required_header>
  <id_info>
    <org_study_id>CO28</org_study_id>
    <nct_id>NCT03259035</nct_id>
  </id_info>
  <brief_title>NEO: Neoadjuvant Chemotherapy, Excision and Observation for Early Rectal Cancer</brief_title>
  <official_title>NEO: Neoadjuvant Chemotherapy, Excision and Observation for Early Rectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Canadian Cancer Trials Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Canadian Cancer Trials Group</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to find out the effects of chemotherapy followed by less&#xD;
      invasive surgery on patients and their early rectal cancer. The approach of this trial will&#xD;
      be considered a success if at least 65% of participants are able to keep the rectum.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 29, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</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>
    <intervention_model_description>This is a two staged, single arm phase II trial of chemotherapy (FOLFOX or CAPOX) followed by tumour excision in patients with early stage rectal cancer</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Measurement of organ preservation rate</measure>
    <time_frame>3 years</time_frame>
    <description>The primary endpoint of this study is the protocol specified organ preservation rate, defined as the proportion of patients with tumour downstaging to ypT0/T1good N0 and who avoid radical surgery. The 95% confidence interval for the organ preservation rate will be calculated</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Locoregional Relapse Rate (LRR)</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Distant Relapse Rate (DRR) estimated based on Kaplan-Meier method</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Free Survival (DFS) estimated based on Kaplan-Meier method</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of post-operative complications</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number and severity of adverse events using CTCAE V5</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life using QLQ-C30</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cost effectiveness using the EQ-5D-5L questionnaire</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">58</enrollment>
  <condition>Rectal Cancer</condition>
  <arm_group>
    <arm_group_label>chemotherapy (FOLFOX or CAPOX) followed by tumour excision</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Folfox Protocol</intervention_name>
    <description>6 cycles of q2weekly FOLFOX, or</description>
    <arm_group_label>chemotherapy (FOLFOX or CAPOX) followed by tumour excision</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capox</intervention_name>
    <description>4 cycles of q3weekly CAPOX</description>
    <arm_group_label>chemotherapy (FOLFOX or CAPOX) followed by tumour excision</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed invasive well-moderately differentiated rectal adenocarcinoma&#xD;
             diagnosed within 90 days prior to enrollment.&#xD;
&#xD;
          -  Tumour stage cT1-T3abN0 based on pelvic MRI&#xD;
&#xD;
               -  cT1N0- tumour invasion into submucosa, no radiographic evidence of mesorectal&#xD;
                  nodal metastasis, tumour deposits or vascular invasion.&#xD;
&#xD;
               -  cT2N0 - tumour invasion into muscularis propria, no radiographic evidence of&#xD;
                  mesorectal nodal metastasis, tumour deposits or vascular invasion.&#xD;
&#xD;
               -  cT3a,bN0- tumour invasion through the muscularis propria no more than 5 mm into&#xD;
                  the subserosa/perirectal tissue and clear of the circumferential radial margin&#xD;
                  (CRM). Absence of radiographic evidence of mesorectal nodal metastasis, tumour&#xD;
                  deposits or lymphovascular invasion.&#xD;
&#xD;
        Note: If the tumour is not visualized in the MRI but there is histological confirmation of&#xD;
        rectal adenocarcinoma the patient is eligible.&#xD;
&#xD;
          -  cN0 stage based on pelvic MRI. Any nodes ≥ 10 mm in longest dimension are considered&#xD;
             malignant, regardless of nodal morphology. For pelvic nodes &lt; 10 mm in longest&#xD;
             dimension, if nodes are seen and are deemed to be morphologically benign in the&#xD;
             opinion of the radiologist and surgeon, the patient is eligible. Patients with visible&#xD;
             pelvic sidewall nodes are excluded&#xD;
&#xD;
          -  M0 stage based on no evidence of metastatic disease by CT imaging.&#xD;
&#xD;
          -  Mid to low-lying tumour eligible for local tumour excision in the opinion of the&#xD;
             treating surgeon.&#xD;
&#xD;
          -  Age of at least 18 years.&#xD;
&#xD;
          -  Medically fit to undergo radical surgery as per treating surgeon's discretion&#xD;
&#xD;
          -  No contraindications to protocol chemotherapy.&#xD;
&#xD;
          -  Adequate normal organ and marrow function as defined below (must be done within 30&#xD;
             days prior to enrolment):&#xD;
&#xD;
               -  ANC ≥ 1.5 x 109/L&#xD;
&#xD;
               -  platelet count ≥100 x 109/L&#xD;
&#xD;
               -  bilirubin &lt; 1.5 ULN, excluding Gilbert's syndrome&#xD;
&#xD;
               -  Calculated creatinine clearance of ≥ 50 ml/min.&#xD;
&#xD;
               -  Clearance to be calculated using Cockcroft formula: Males: 1.23 x (140 - age) x&#xD;
                  weight (kg) - serum creatinine (μmol/l) ; Females: 1.05 x (140 - age) x weight&#xD;
                  (kg) - serum creatinine (μmol/l)&#xD;
&#xD;
          -  The patient must have an ECOG performance status of 0, 1.&#xD;
&#xD;
          -  Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life&#xD;
             and health utility questionnaires.&#xD;
&#xD;
          -  Patient consent must be appropriately obtained in accordance with applicable local and&#xD;
             regulatory requirements. Each patient must sign a consent form prior to enrollment in&#xD;
             the trial to document their willingness to participate.&#xD;
&#xD;
          -  Must be accessible for treatment and follow up. Patients registered on this trial must&#xD;
             be treated with chemotherapy and followed at the enrolling centre.&#xD;
&#xD;
          -  Protocol treatment is to begin within 5 working days of patient enrollment.&#xD;
&#xD;
          -  Women/men of childbearing potential must have agreed to use a highly effective&#xD;
             contraceptive method during and for 6 months after completion of chemotherapy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient has pathologic high risk factors on either the initial biopsy specimen report&#xD;
             or follow-up biopsy (if done): high histologic grade, mucinous histology, lymphatic or&#xD;
             vascular invasion.&#xD;
&#xD;
          -  History of other malignancies, except: adequately treated non-melanoma skin cancer,&#xD;
             curatively treated in-situ cancer of the cervix, or other solid tumours curatively&#xD;
             treated with no evidence of disease for ≥ 5 years.&#xD;
&#xD;
          -  Synchronous cancer.&#xD;
&#xD;
          -  Prior treatment for rectal cancer.&#xD;
&#xD;
          -  Previous pelvic radiation for any reason.&#xD;
&#xD;
          -  Patients with known dihydropyrimidine dehydrogenase deficiency&#xD;
&#xD;
          -  Treatment with other investigational drugs or anti-cancer therapy within 28 days prior&#xD;
             to enrolment.&#xD;
&#xD;
          -  Clinically significant (i.e. active) cardiovascular disease for example cerebro&#xD;
             vascular accidents (&lt; 6 months prior to enrolment), myocardial infarction (&lt; 6 months&#xD;
             prior to enrolment), unstable angina, New York Heart Association (NYHA) grade II or&#xD;
             higher, congestive heart failure, serious cardiac arrhythmia requiring medication.&#xD;
&#xD;
          -  Any contra-indications to undergo MRI imaging.&#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>Hagen Kennecke</last_name>
    <role>Study Chair</role>
    <affiliation>Virginia Mason Medical Centre, WA USA</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Carl Brown</last_name>
    <role>Study Chair</role>
    <affiliation>St. Paul's Hospital, Vancouver BC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UC Irvine Medical Center</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Mason Medical Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>97101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>BCCA - Vancouver Cancer Centre</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V5Z 4E6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Paul's Hospital</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V6Z 1Y6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CancerCare Manitoba</name>
      <address>
        <city>Winnipeg</city>
        <state>Manitoba</state>
        <zip>R3E 0V9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>QEII Health Sciences Centre</name>
      <address>
        <city>Halifax</city>
        <state>Nova Scotia</state>
        <zip>B3H 1V7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kingston Health Sciences Centre</name>
      <address>
        <city>Kingston</city>
        <state>Ontario</state>
        <zip>K7L 2V7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ottawa Hospital Research Institute</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1H 8L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Health Sciences North</name>
      <address>
        <city>Sudbury</city>
        <state>Ontario</state>
        <zip>P3E 5J1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Research Institute of the McGill University</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H4A 3J1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Kennecke HF, O'Callaghan CJ, Loree JM, Moloo H, Auer R, Jonker DJ, Raval M, Musselman R, Ma G, Caycedo-Marulanda A, Simianu VV, Patel S, Pitre LD, Helewa R, Gordon VL, Neumann K, Nimeiri H, Sherry M, Tu D, Brown CJ. Neoadjuvant Chemotherapy, Excision, and Observation for Early Rectal Cancer: The Phase II NEO Trial (CCTG CO.28) Primary End Point Results. J Clin Oncol. 2023 Jan 10;41(2):233-242. doi: 10.1200/JCO.22.00184. Epub 2022 Aug 18.</citation>
    <PMID>35981270</PMID>
  </results_reference>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>August 21, 2017</study_first_submitted>
  <study_first_submitted_qc>August 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 23, 2017</study_first_posted>
  <last_update_submitted>August 3, 2023</last_update_submitted>
  <last_update_submitted_qc>August 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 4, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rectal Neoplasms</mesh_term>
  </condition_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/NCT03259035
org study id: CO28
nct id: NCT03259035
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this study is to find out the effects of chemotherapy followed by less
      invasive surgery on patients and their early rectal cancer. The approach of this trial will
      be considered a success if at least 65% of participants are able to keep the rectum.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: This is a two staged, single arm phase II trial of chemotherapy (FOLFOX or CAPOX) followed by tumour excision in patients with early stage rectal cancer
primary purpose: Treatment
masking: None (Open Label)
measure: Measurement of organ preservation rate
time frame: 3 years
description: The primary endpoint of this study is the protocol specified organ preservation rate, defined as the proportion of patients with tumour downstaging to ypT0/T1good N0 and who avoid radical surgery. The 95% confidence interval for the organ preservation rate will be calculated
measure: Locoregional Relapse Rate (LRR)
time frame: 3 years
measure: Distant Relapse Rate (DRR) estimated based on Kaplan-Meier method
time frame: 3 years
measure: Disease Free Survival (DFS) estimated based on Kaplan-Meier method
time frame: 3 years
measure: Rate of post-operative complications
time frame: 3 years
measure: Number and severity of adverse events using CTCAE V5
time frame: 3 years
measure: Quality of Life using QLQ-C30
time frame: 3 years
measure: Cost effectiveness using the EQ-5D-5L questionnaire
time frame: 3 years
arm group label: chemotherapy (FOLFOX or CAPOX) followed by tumour excision
arm group type: Experimental
intervention type: Drug
intervention name: Folfox Protocol
description: 6 cycles of q2weekly FOLFOX, or
arm group label: chemotherapy (FOLFOX or CAPOX) followed by tumour excision
intervention type: Drug
intervention name: Capox
description: 4 cycles of q3weekly CAPOX
arm group label: chemotherapy (FOLFOX or CAPOX) followed by tumour excision
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Hagen Kennecke
role: Study Chair
affiliation: Virginia Mason Medical Centre, WA USA
last name: Carl Brown
role: Study Chair
affiliation: St. Paul's Hospital, Vancouver BC
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: United States
citation: Kennecke HF, O'Callaghan CJ, Loree JM, Moloo H, Auer R, Jonker DJ, Raval M, Musselman R, Ma G, Caycedo-Marulanda A, Simianu VV, Patel S, Pitre LD, Helewa R, Gordon VL, Neumann K, Nimeiri H, Sherry M, Tu D, Brown CJ. Neoadjuvant Chemotherapy, Excision, and Observation for Early Rectal Cancer: The Phase II NEO Trial (CCTG CO.28) Primary End Point Results. J Clin Oncol. 2023 Jan 10;41(2):233-242. doi: 10.1200/JCO.22.00184. Epub 2022 Aug 18.
PMID: 35981270
responsible party type: Sponsor
mesh term: Rectal Neoplasms
sharing ipd: No