<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/NCT04486131</url>
  </required_header>
  <id_info>
    <org_study_id>A2021.0524.0001</org_study_id>
    <nct_id>NCT04486131</nct_id>
  </id_info>
  <brief_title>Lateral Nodal Recurrence in Rectal Cancer</brief_title>
  <acronym>LaNoReC</acronym>
  <official_title>Lateral Nodal Recurrence in Rectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Amsterdam UMC, location VUmc</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Amsterdam UMC, location VUmc</source>
  <oversight_info>
    <has_dmc>No</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>
      Local recurrence rates in rectal cancer have reduced dramatically since the introduction of&#xD;
      the total mesorectal excision (TME) technique and neoadjuvant (chemo)radiotherapy (C))RT) to&#xD;
      overall rates of 5-year local recurrence to 5-10%.&#xD;
&#xD;
      However, distal rectal cancers have a tendency to spread to lateral lymph nodes and it was&#xD;
      recently shown that patients with enlarged lateral lymph nodes of ≥7mm short-axis size have a&#xD;
      considerable chance of a local recurrence: 15-20%. This is regardless of CRT with TME in two&#xD;
      retrospective cohorts (Lateral Node Consortium and Snapshot Rectal Cancer 2016 study).&#xD;
      According to the Lateral Node Consortium study, this rate was significantly reduced to &lt;6%&#xD;
      when performing a lateral lymph node dissection (LLND) after (C)RT + TME.&#xD;
&#xD;
      A major drawback of these recent multi-center studies is their retrospective nature.&#xD;
      Therefore, in the Netherlands, radiologists, radiation oncologists, surgeons and pathologists&#xD;
      have recently been educated and trained to enhance knowledge and awareness of LLNs and to&#xD;
      implement nerve-sparing minimally invasive LLND.&#xD;
&#xD;
      The LaNoReC trial is a prospective registration study aimed at evaluating oncological&#xD;
      outcomes after multi-disciplinary training. The main question of this study is whether, after&#xD;
      dedicated training and the performance of LLNDs, the lateral local recurrence rate in rectal&#xD;
      cancers with enlarged nodes (≥7mm) can be reduced to below 6%.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Local recurrence rates in rectal cancer have reduced dramatically since the introduction of&#xD;
      the total mesorectal excision (TME) technique. These rates have been lowered further with the&#xD;
      use of neoadjuvant (chemo)radiotherapy ((C)RT) regimens in appropriate cases, decreasing&#xD;
      overall rates of 5-year local recurrence to 5-10%. However, in patients with enlarged lateral&#xD;
      lymph nodes (LLNs, ≥7mm short-axis size), recurrence rates have remained high, up to 20%.&#xD;
      Most likely, this is caused by lymphatic spread of low rectal cancer to the lateral&#xD;
      compartments. Western surgeons have always relied on (C)RT to sterilize the lateral&#xD;
      compartments, containing the internal iliac and obturator lymph nodes, alleviating fears of&#xD;
      operative morbidity and nerve function disorders associated with a lateral lymph node&#xD;
      dissection (LLND), mainly performed in the East. Furthermore, most Western clinicians&#xD;
      consider lateral nodal disease to represent metastatic disease, not amendable to cure.&#xD;
&#xD;
      The Lateral Node Consortium undertook a multi-centre study with 12 centres from seven&#xD;
      countries, collecting data over a 5-year period, including all consecutive patients operated&#xD;
      for a cT3 or T4 rectal cancer. In all patients, every series of MRIs was re-reviewed by a&#xD;
      standardized protocol, examining lateral pelvic nodes, defining these according to size and&#xD;
      the presence of malignant features and relating these to the development of locally recurrent&#xD;
      disease. In the first publication of the consortium with a total of 1216 patients, it was&#xD;
      shown that pre-treatment lateral lymph node (LLN) size of ≥7 mm, results in an unacceptably&#xD;
      high incidence of lateral local recurrence of 20%, despite (C)RT with TME. Within the&#xD;
      consortium, several centres performed LLND's after (C)RT, which resulted in a significantly&#xD;
      lower rate of lateral local recurrence of 6% in nodes ≥7 mm (p = 0.042). Furthermore, LLN&#xD;
      enlargement did not influence distant metastases rate, suggesting it is a local issue which&#xD;
      requires to be addressed through targeted treatment in the pelvis, rather simply representing&#xD;
      a marker of poor prognosis and distant disease.&#xD;
&#xD;
      Additionally, a second study, the Snapshot Rectal Cancer 2016 was conducted in 2020. This&#xD;
      national retrospective cohort study included 3057 patients operated for rectal cancer in 2016&#xD;
      with a 4-year follow-up period. Radiologists were trained for LLN classification and&#xD;
      measurements and re-reviewed MRIs of 882 patients with low (≤8cm from the anorectal&#xD;
      junction), cT3/4 rectal cancer who received neoadjuvant (chemo)radiotherapy with the help of&#xD;
      two atlases. This study found a 4-year LLR risk of 15% in presence of enlarged LLNs.&#xD;
&#xD;
      The major drawback of these multi-center studies are their retrospective nature. Radiological&#xD;
      reporting of LLNs was low for primary MRIs, which may have influenced treatment decisions.&#xD;
      Consequently, LLNs may have not been separately included in irradiation field. Moreover,&#xD;
      neither study was able to investigate the effect of LLND in a trained setting. In the&#xD;
      Netherlands, radiologists, radiation oncologists, surgeons and pathologists have recently&#xD;
      been educated and trained to enhance knowledge and awareness of LLNs and to implement&#xD;
      nerve-sparing minimally invasive LLND. The LaNoReC describes a prospective evaluation of&#xD;
      oncological outcomes after multi-disciplinary training, thereby aiming for a 50% reduction in&#xD;
      LLR rates.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 6, 2020</start_date>
  <completion_date type="Anticipated">October 2026</completion_date>
  <primary_completion_date type="Anticipated">October 2026</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Lateral local recurrence</measure>
    <time_frame>3 years</time_frame>
    <description>Lateral local recurrence diagnosed during the follow up</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease-free survival</measure>
    <time_frame>3 years</time_frame>
    <description>The measure of time after treatment during which no sign of cancer is found.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall patient survival</measure>
    <time_frame>3 years</time_frame>
    <description>The percentage of people who are alive 3 years after the surgery.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Morbidity and functional outcomes assessed by LARS questions</measure>
    <time_frame>3 years</time_frame>
    <description>Use of questionnaire LARS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life as assessed by the EORTC QLQ-CR29</measure>
    <time_frame>3 years</time_frame>
    <description>Quality of life as assessed by the EORTC QLQ-CR29</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life as assessed by the EQ-5D</measure>
    <time_frame>3 years</time_frame>
    <description>Quality of life as assessed by the EQ-5D</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life as assessed by the QLQ-C30</measure>
    <time_frame>3 years</time_frame>
    <description>Quality of life as assessed by the QLQ-C30</description>
  </secondary_outcome>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Rectal Cancer</condition>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with rectal cancer with one or more lateral nodes with a short-axis of ≥7mm or&#xD;
        ≥5mm with one or more malignant features (i.e. round shape, irregular margins,&#xD;
        heterogeneity, loss of fatty hilum).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        • All patients with rectal cancer with one or more lateral nodes with a short-axis of ≥7mm&#xD;
        or ≥5mm with one or more malignant features (i.e. round shape, irregular margins,&#xD;
        heterogeneity, loss of fatty hilum).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Younger than 18 years old&#xD;
&#xD;
          -  Pelvic irradiation in the medical history&#xD;
&#xD;
          -  Previous lateral lymph node dissection related to pelvic malignancy&#xD;
&#xD;
          -  Synchronous distant metastases&#xD;
&#xD;
          -  Familiar adenomatous polyposis&#xD;
&#xD;
          -  Synchronous colon cancer with a higher stage than rectal cancer&#xD;
&#xD;
          -  Absolute contraindication for general anaesthesia&#xD;
&#xD;
          -  Pregnancy&#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>Miranda Kusters, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>VUMedicalCentre</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Miranda Kusters, MD, PhD</last_name>
    <phone>0031204444444</phone>
    <email>m.kusters@amsterdamumc.nl</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Eline van Geffen, MD</last_name>
    <phone>0031204444444</phone>
    <email>lanorec@amsterdamumc.nl</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Amsterdam University Medical Centers</name>
      <address>
        <city>Amsterdam</city>
        <state>North-Holland</state>
        <zip>1081 HV</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Miranda Kusters, MD, PhD</last_name>
      <phone>003120-4444444</phone>
      <email>m.kusters@amsterdamumc.nl</email>
    </contact>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <results_reference>
    <citation>Ogura A, Konishi T, Cunningham C, Garcia-Aguilar J, Iversen H, Toda S, Lee IK, Lee HX, Uehara K, Lee P, Putter H, van de Velde CJH, Beets GL, Rutten HJT, Kusters M; Lateral Node Study Consortium. Neoadjuvant (Chemo)radiotherapy With Total Mesorectal Excision Only Is Not Sufficient to Prevent Lateral Local Recurrence in Enlarged Nodes: Results of the Multicenter Lateral Node Study of Patients With Low cT3/4 Rectal Cancer. J Clin Oncol. 2019 Jan 1;37(1):33-43. doi: 10.1200/JCO.18.00032. Epub 2018 Nov 7.</citation>
    <PMID>30403572</PMID>
  </results_reference>
  <results_reference>
    <citation>Ogura A, Konishi T, Beets GL, Cunningham C, Garcia-Aguilar J, Iversen H, Toda S, Lee IK, Lee HX, Uehara K, Lee P, Putter H, van de Velde CJH, Rutten HJT, Tuynman JB, Kusters M; Lateral Node Study Consortium. Lateral Nodal Features on Restaging Magnetic Resonance Imaging Associated With Lateral Local Recurrence in Low Rectal Cancer After Neoadjuvant Chemoradiotherapy or Radiotherapy. JAMA Surg. 2019 Sep 1;154(9):e192172. doi: 10.1001/jamasurg.2019.2172. Epub 2019 Sep 18.</citation>
    <PMID>31268504</PMID>
  </results_reference>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>June 30, 2020</study_first_submitted>
  <study_first_submitted_qc>July 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2020</study_first_posted>
  <last_update_submitted>January 16, 2023</last_update_submitted>
  <last_update_submitted_qc>January 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 19, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Amsterdam UMC, location VUmc</investigator_affiliation>
    <investigator_full_name>M. Kusters</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rectal Neoplasms</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>IPD data that underlie results in a publication can be made available upon reasonable request</ipd_description>
    <ipd_time_frame>Starting after initial publication of data</ipd_time_frame>
    <ipd_access_criteria>Requests will be assessed by the study team</ipd_access_criteria>
  </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/NCT04486131
org study id: A2021.0524.0001
nct id: NCT04486131
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Local recurrence rates in rectal cancer have reduced dramatically since the introduction of
      the total mesorectal excision (TME) technique and neoadjuvant (chemo)radiotherapy (C))RT) to
      overall rates of 5-year local recurrence to 5-10%.

      However, distal rectal cancers have a tendency to spread to lateral lymph nodes and it was
      recently shown that patients with enlarged lateral lymph nodes of ≥7mm short-axis size have a
      considerable chance of a local recurrence: 15-20%. This is regardless of CRT with TME in two
      retrospective cohorts (Lateral Node Consortium and Snapshot Rectal Cancer 2016 study).
      According to the Lateral Node Consortium study, this rate was significantly reduced to <6%
      when performing a lateral lymph node dissection (LLND) after (C)RT + TME.

      A major drawback of these recent multi-center studies is their retrospective nature.
      Therefore, in the Netherlands, radiologists, radiation oncologists, surgeons and pathologists
      have recently been educated and trained to enhance knowledge and awareness of LLNs and to
      implement nerve-sparing minimally invasive LLND.

      The LaNoReC trial is a prospective registration study aimed at evaluating oncological
      outcomes after multi-disciplinary training. The main question of this study is whether, after
      dedicated training and the performance of LLNDs, the lateral local recurrence rate in rectal
      cancers with enlarged nodes (≥7mm) can be reduced to below 6%.
Local recurrence rates in rectal cancer have reduced dramatically since the introduction of
      the total mesorectal excision (TME) technique. These rates have been lowered further with the
      use of neoadjuvant (chemo)radiotherapy ((C)RT) regimens in appropriate cases, decreasing
      overall rates of 5-year local recurrence to 5-10%. However, in patients with enlarged lateral
      lymph nodes (LLNs, ≥7mm short-axis size), recurrence rates have remained high, up to 20%.
      Most likely, this is caused by lymphatic spread of low rectal cancer to the lateral
      compartments. Western surgeons have always relied on (C)RT to sterilize the lateral
      compartments, containing the internal iliac and obturator lymph nodes, alleviating fears of
      operative morbidity and nerve function disorders associated with a lateral lymph node
      dissection (LLND), mainly performed in the East. Furthermore, most Western clinicians
      consider lateral nodal disease to represent metastatic disease, not amendable to cure.

      The Lateral Node Consortium undertook a multi-centre study with 12 centres from seven
      countries, collecting data over a 5-year period, including all consecutive patients operated
      for a cT3 or T4 rectal cancer. In all patients, every series of MRIs was re-reviewed by a
      standardized protocol, examining lateral pelvic nodes, defining these according to size and
      the presence of malignant features and relating these to the development of locally recurrent
      disease. In the first publication of the consortium with a total of 1216 patients, it was
      shown that pre-treatment lateral lymph node (LLN) size of ≥7 mm, results in an unacceptably
      high incidence of lateral local recurrence of 20%, despite (C)RT with TME. Within the
      consortium, several centres performed LLND's after (C)RT, which resulted in a significantly
      lower rate of lateral local recurrence of 6% in nodes ≥7 mm (p = 0.042). Furthermore, LLN
      enlargement did not influence distant metastases rate, suggesting it is a local issue which
      requires to be addressed through targeted treatment in the pelvis, rather simply representing
      a marker of poor prognosis and distant disease.

      Additionally, a second study, the Snapshot Rectal Cancer 2016 was conducted in 2020. This
      national retrospective cohort study included 3057 patients operated for rectal cancer in 2016
      with a 4-year follow-up period. Radiologists were trained for LLN classification and
      measurements and re-reviewed MRIs of 882 patients with low (≤8cm from the anorectal
      junction), cT3/4 rectal cancer who received neoadjuvant (chemo)radiotherapy with the help of
      two atlases. This study found a 4-year LLR risk of 15% in presence of enlarged LLNs.

      The major drawback of these multi-center studies are their retrospective nature. Radiological
      reporting of LLNs was low for primary MRIs, which may have influenced treatment decisions.
      Consequently, LLNs may have not been separately included in irradiation field. Moreover,
      neither study was able to investigate the effect of LLND in a trained setting. In the
      Netherlands, radiologists, radiation oncologists, surgeons and pathologists have recently
      been educated and trained to enhance knowledge and awareness of LLNs and to implement
      nerve-sparing minimally invasive LLND. The LaNoReC describes a prospective evaluation of
      oncological outcomes after multi-disciplinary training, thereby aiming for a 50% reduction in
      LLR rates.
observational model: Other
time perspective: Prospective
measure: Lateral local recurrence
time frame: 3 years
description: Lateral local recurrence diagnosed during the follow up
measure: Disease-free survival
time frame: 3 years
description: The measure of time after treatment during which no sign of cancer is found.
measure: Overall patient survival
time frame: 3 years
description: The percentage of people who are alive 3 years after the surgery.
measure: Morbidity and functional outcomes assessed by LARS questions
time frame: 3 years
description: Use of questionnaire LARS
measure: Quality of life as assessed by the EORTC QLQ-CR29
time frame: 3 years
description: Quality of life as assessed by the EORTC QLQ-CR29
measure: Quality of life as assessed by the EQ-5D
time frame: 3 years
description: Quality of life as assessed by the EQ-5D
measure: Quality of life as assessed by the QLQ-C30
time frame: 3 years
description: Quality of life as assessed by the QLQ-C30
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Miranda Kusters, MD, PhD
role: Principal Investigator
affiliation: VUMedicalCentre
last name: Miranda Kusters, MD, PhD
phone: 0031204444444
email: m.kusters@amsterdamumc.nl
last name: Eline van Geffen, MD
phone: 0031204444444
email: lanorec@amsterdamumc.nl
facility: 
status: Recruiting
contact: 
country: Netherlands
citation: Ogura A, Konishi T, Cunningham C, Garcia-Aguilar J, Iversen H, Toda S, Lee IK, Lee HX, Uehara K, Lee P, Putter H, van de Velde CJH, Beets GL, Rutten HJT, Kusters M; Lateral Node Study Consortium. Neoadjuvant (Chemo)radiotherapy With Total Mesorectal Excision Only Is Not Sufficient to Prevent Lateral Local Recurrence in Enlarged Nodes: Results of the Multicenter Lateral Node Study of Patients With Low cT3/4 Rectal Cancer. J Clin Oncol. 2019 Jan 1;37(1):33-43. doi: 10.1200/JCO.18.00032. Epub 2018 Nov 7.
PMID: 30403572
citation: Ogura A, Konishi T, Beets GL, Cunningham C, Garcia-Aguilar J, Iversen H, Toda S, Lee IK, Lee HX, Uehara K, Lee P, Putter H, van de Velde CJH, Rutten HJT, Tuynman JB, Kusters M; Lateral Node Study Consortium. Lateral Nodal Features on Restaging Magnetic Resonance Imaging Associated With Lateral Local Recurrence in Low Rectal Cancer After Neoadjuvant Chemoradiotherapy or Radiotherapy. JAMA Surg. 2019 Sep 1;154(9):e192172. doi: 10.1001/jamasurg.2019.2172. Epub 2019 Sep 18.
PMID: 31268504
responsible party type: Principal Investigator
investigator affiliation: Amsterdam UMC, location VUmc
investigator full name: M. Kusters
investigator title: Principal Investigator
mesh term: Rectal Neoplasms
mesh term: Recurrence
sharing ipd: Yes
ipd description: IPD data that underlie results in a publication can be made available upon reasonable request
ipd time frame: Starting after initial publication of data
ipd access criteria: Requests will be assessed by the study team