<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/NCT03001362</url>
  </required_header>
  <id_info>
    <org_study_id>14-407 GEN</org_study_id>
    <nct_id>NCT03001362</nct_id>
  </id_info>
  <brief_title>Patients With Rectal Cancer: a &quot;Wait-and-see&quot; Approach</brief_title>
  <official_title>Radical External Beam Chemoradiation in Patients With Rectal Cancer: a &quot;Wait-and-see&quot; Approach</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>McGill University Health Centre/Research Institute of the McGill University Health Centre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>McGill University Health Centre/Research Institute of the McGill University Health Centre</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with histologically proven adenocarcinoma of the rectum will receive pelvic&#xD;
      radiotherapy to a dose of 45Gy in 25 fractions with a tumor boost to a dose of 9Gy in 5&#xD;
      fractions (thus total of 54Gy/30Fx to the primary tumor), combined with radio sensitizing&#xD;
      chemotherapy. Patients will then be closely monitored, through endoscopy and imaging, for&#xD;
      response to treatment and relapse. Salvage oncologic surgery to be offered if there is&#xD;
      failure to achieve complete clinical response or in the event of a loco regional relapse.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The combination of preoperative (chemo)radiotherapy and total mesorectal excision (TME) has&#xD;
      been shown to reduce the risk of local recurrence in patients with resectable adenocarcinoma&#xD;
      of the rectum. The improved local control rates come at the price of an increased risk of&#xD;
      surgical complications, including a postoperative death rate of 2-8 percent which may reach&#xD;
      30 per cent at 6 months in those aged over 85 years, as well as long-term impact on&#xD;
      anorectal, urinary and sexual function. Patients with cancers in the low rectum in close&#xD;
      proximity to the sphincter muscles, may require a permanent stoma, which can be associated&#xD;
      with high psychological morbidity.&#xD;
&#xD;
      Preoperative chemoradiotherapy followed by a delay to resection can produce pathological&#xD;
      complete responses. One review of phase II and III studies identified an overall pCR rate of&#xD;
      13.5%, but even higher rates of pCR have been observed with doses of radiotherapy exceeding&#xD;
      45 Gy . Certainly patients who proceed to radical surgery after achieving a pCR with chemo&#xD;
      radiation do have favorable long-term outcomes. But do patients whose tumor has already been&#xD;
      sterilized by chemo radiotherapy need to proceed with radical surgery?&#xD;
&#xD;
      A number of studies have now emerged highlighting the rationale of a 'wait and see' policy&#xD;
      for patients who achieve a complete clinical response (cCR) after chemo radiotherapy. The&#xD;
      majority of the clinical data supporting this approach have come from Brazil. The Brazilian&#xD;
      data suggests that observation of such patients yields survival rates similar to those of&#xD;
      patients who undergo radical surgery with confirmation of pCR. More recent studies from the&#xD;
      United Kingdom and the Netherlands appear to support the feasibility of this approach. To&#xD;
      date there is no published prospectively collected data of a wait-and-see policy from a North&#xD;
      American Centre.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date>March 2015</start_date>
  <completion_date type="Anticipated">September 2025</completion_date>
  <primary_completion_date type="Anticipated">March 2023</primary_completion_date>
  <phase>N/A</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Feasibility of a &quot;wait and see&quot; approach</measure>
    <time_frame>One year</time_frame>
    <description>Rate of failure to achieve CR or the rate of recurrence after achieving CR</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">48</enrollment>
  <condition>Colorectal Carcinoma</condition>
  <arm_group>
    <arm_group_label>Radical External Beam RT for Colorectal Ca</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single arm consisting of: Radical external beam RT dose of 54 Gy in 30fx with radiosensitizing chemotherapy as per institutional standard</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radical external beam radiotherapy</intervention_name>
    <description>pelvic radiotherapy to a dose of 45 Gy in 25 fractions with a tumor boost to a dose of 9 Gy in 5 fractions (thus total of 54 Gy/30 fractions to the primary tumor), combined with radio sensitizing chemotherapy.</description>
    <arm_group_label>Radical External Beam RT for Colorectal Ca</arm_group_label>
    <other_name>Radiosensitizing chemotherapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pelvic MRI defined disease (at least one of the following):&#xD;
&#xD;
               -  mesorectum involved or breached - includes involvement of adjacent organ (s)&#xD;
                  (T3-T4)&#xD;
&#xD;
               -  involvement of muscularis propria (T2)&#xD;
&#xD;
               -  extra-mural vascular invasion&#xD;
&#xD;
               -  tumour deposit within the mesorectum&#xD;
&#xD;
               -  one or more involved mesorectal lymph node&#xD;
&#xD;
          -  Patients are considered medically fit for oncologic resection&#xD;
&#xD;
          -  ECOG performance status 0 or 1&#xD;
&#xD;
          -  No evidence of established metastatic disease (CT chest and abdomen)&#xD;
&#xD;
          -  Absolute neutrophil count &gt;1.5x109/L; platelets &gt;100x109/L,&#xD;
&#xD;
          -  Serum transaminase &lt;3 x ULN;&#xD;
&#xD;
          -  Adequate renal function (Cockroft Gault estimation &gt;50 mL/min)&#xD;
&#xD;
          -  Bilirubin &lt;1.5 x ULN&#xD;
&#xD;
          -  Ability to comply with oral medication&#xD;
&#xD;
          -  Willingness and ability to give informed consent and comply with treatment and follow&#xD;
             up schedule&#xD;
&#xD;
          -  Age 18 or over&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous radiotherapy to the pelvis (including brachytherapy)&#xD;
&#xD;
          -  Enlarged extramesorectal nodes&#xD;
&#xD;
          -  Uncontrolled cardiorespiratory comorbidity (includes patients with inadequately&#xD;
             controlled angina or myocardial infarction within 6 months of randomisation)&#xD;
&#xD;
          -  T1N0 disease without extra-mural venous invasion&#xD;
&#xD;
          -  Unequivocal evidence of metastatic disease (includes resectable metastases)&#xD;
&#xD;
          -  Major impairment of bowel function without defunctioning stoma/ileostomy (baseline&#xD;
             grade 3 diarrhoea or clinically significant faecal incontinence)&#xD;
&#xD;
          -  History of another malignancy within the last 5 years except successfully treated&#xD;
             basal cell cancer of skin or carcinoma in situ of uterine cervix.&#xD;
&#xD;
          -  Known dihydropyrimidine dehydrogenase deficiency&#xD;
&#xD;
          -  Known Gilberts disease (hyperbilirubinaemia)&#xD;
&#xD;
          -  Taking warfarin or phenytoin or sorivudine&#xD;
&#xD;
          -  Gastrointestinal disorder which would interfere with oral therapy and its&#xD;
             bioavailability&#xD;
&#xD;
          -  Pregnant, lactating, or pre-menopausal women not using adequate contraception&#xD;
&#xD;
          -  Unfit to receive any study treatment or subsequent surgical resection&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Neil Kopek, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Radiation Oncologist</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Neil Kopek, M.D.</last_name>
    <phone>514-934-4440</phone>
    <email>neil.kopek@muhc.mcgill.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Marianna Perna, CCRP,CCRC</last_name>
    <phone>514-934-1934</phone>
    <phone_ext>43191</phone_ext>
    <email>marianna.perna@muhc.mcgill.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>McGill University Health Centre- Cedars Cancer Centre</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H4A 3J1</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Neil Kopek, M.D.</last_name>
      <phone>514-934-4440</phone>
      <email>neil.kopek@muhc.mcgill.ca</email>
    </contact>
    <contact_backup>
      <last_name>Marianna Perna, CCRP, CCRC</last_name>
      <phone>514-934-1934</phone>
      <phone_ext>43191</phone_ext>
      <email>marianna.perna@muhc.mcgill.ca</email>
    </contact_backup>
    <investigator>
      <last_name>Neil Kopek, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>McGill University Health Center-Cedars Cancer Centre</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H4A 3J1</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marianna Perna, CCRP,CCRC</last_name>
      <phone>514-934-1934</phone>
      <phone_ext>43191</phone_ext>
      <email>marianna.perna@muhc.mcgill.ca</email>
    </contact>
    <contact_backup>
      <last_name>Tatiana Carvalho, CCRP</last_name>
      <phone>514-934-1934</phone>
      <phone_ext>43698</phone_ext>
      <email>tatiana.carvalho@muhc.mcgill.ca</email>
    </contact_backup>
    <investigator>
      <last_name>Sergio Faria, M.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Tarek Hijal, M.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Caroline Reinhart, M.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Giovanni Artho, M.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jamil Asselah, M.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ragu Rajan, M.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Marie Van-Huyse, M.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Sender Lieberman, M.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Patrick Charlebois, M.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Ollier JC; EORTC Radiotherapy Group Trial 22921. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006 Sep 14;355(11):1114-23. doi: 10.1056/NEJMoa060829. Erratum In: N Engl J Med. 2007 Aug 16;357(7):728.</citation>
    <PMID>16971718</PMID>
  </reference>
  <reference>
    <citation>Gerard JP, Conroy T, Bonnetain F, Bouche O, Chapet O, Closon-Dejardin MT, Untereiner M, Leduc B, Francois E, Maurel J, Seitz JF, Buecher B, Mackiewicz R, Ducreux M, Bedenne L. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006 Oct 1;24(28):4620-5. doi: 10.1200/JCO.2006.06.7629.</citation>
    <PMID>17008704</PMID>
  </reference>
  <reference>
    <citation>Peeters KC, Marijnen CA, Nagtegaal ID, Kranenbarg EK, Putter H, Wiggers T, Rutten H, Pahlman L, Glimelius B, Leer JW, van de Velde CJ; Dutch Colorectal Cancer Group. The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma. Ann Surg. 2007 Nov;246(5):693-701. doi: 10.1097/01.sla.0000257358.56863.ce.</citation>
    <PMID>17968156</PMID>
  </reference>
  <reference>
    <citation>Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R; German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004 Oct 21;351(17):1731-40. doi: 10.1056/NEJMoa040694.</citation>
    <PMID>15496622</PMID>
  </reference>
  <reference>
    <citation>Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, Quirke P, Couture J, de Metz C, Myint AS, Bessell E, Griffiths G, Thompson LC, Parmar M. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009 Mar 7;373(9666):811-20. doi: 10.1016/S0140-6736(09)60484-0.</citation>
    <PMID>19269519</PMID>
  </reference>
  <reference>
    <citation>van Gijn W, Marijnen CA, Nagtegaal ID, Kranenbarg EM, Putter H, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van de Velde CJ; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol. 2011 Jun;12(6):575-82. doi: 10.1016/S1470-2045(11)70097-3. Epub 2011 May 17.</citation>
    <PMID>21596621</PMID>
  </reference>
  <reference>
    <citation>Borowski DW, Bradburn DM, Mills SJ, Bharathan B, Wilson RG, Ratcliffe AA, Kelly SB; Northern Region Colorectal Cancer Audit Group (NORCCAG). Volume-outcome analysis of colorectal cancer-related outcomes. Br J Surg. 2010 Sep;97(9):1416-30. doi: 10.1002/bjs.7111.</citation>
    <PMID>20632311</PMID>
  </reference>
  <reference>
    <citation>Paun BC, Cassie S, MacLean AR, Dixon E, Buie WD. Postoperative complications following surgery for rectal cancer. Ann Surg. 2010 May;251(5):807-18. doi: 10.1097/SLA.0b013e3181dae4ed.</citation>
    <PMID>20395841</PMID>
  </reference>
  <reference>
    <citation>Rutten HJ, den Dulk M, Lemmens VE, van de Velde CJ, Marijnen CA. Controversies of total mesorectal excision for rectal cancer in elderly patients. Lancet Oncol. 2008 May;9(5):494-501. doi: 10.1016/S1470-2045(08)70129-3.</citation>
    <PMID>18452860</PMID>
  </reference>
  <reference>
    <citation>Bujko K, Nowacki MP, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Kryj M. Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg. 2006 Oct;93(10):1215-23. doi: 10.1002/bjs.5506.</citation>
    <PMID>16983741</PMID>
  </reference>
  <reference>
    <citation>Gervaz PA, Wexner SD, Pemberton JH. Pelvic radiation and anorectal function: introducing the concept of sphincter-preserving radiation therapy. J Am Coll Surg. 2002 Sep;195(3):387-94. doi: 10.1016/s1072-7515(02)01308-x. No abstract available.</citation>
    <PMID>12229948</PMID>
  </reference>
  <reference>
    <citation>Hartley A, Ho KF, McConkey C, Geh JI. Pathological complete response following pre-operative chemoradiotherapy in rectal cancer: analysis of phase II/III trials. Br J Radiol. 2005 Oct;78(934):934-8. doi: 10.1259/bjr/86650067.</citation>
    <PMID>16177017</PMID>
  </reference>
  <reference>
    <citation>Maas M, Nelemans PJ, Valentini V, Das P, Rodel C, Kuo LJ, Calvo FA, Garcia-Aguilar J, Glynne-Jones R, Haustermans K, Mohiuddin M, Pucciarelli S, Small W Jr, Suarez J, Theodoropoulos G, Biondo S, Beets-Tan RG, Beets GL. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010 Sep;11(9):835-44. doi: 10.1016/S1470-2045(10)70172-8. Epub 2010 Aug 6.</citation>
    <PMID>20692872</PMID>
  </reference>
  <reference>
    <citation>Habr-Gama A, Perez RO, Proscurshim I, Campos FG, Nadalin W, Kiss D, Gama-Rodrigues J. Patterns of failure and survival for nonoperative treatment of stage c0 distal rectal cancer following neoadjuvant chemoradiation therapy. J Gastrointest Surg. 2006 Dec;10(10):1319-28; discussion 1328-9. doi: 10.1016/j.gassur.2006.09.005.</citation>
    <PMID>17175450</PMID>
  </reference>
  <reference>
    <citation>Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro U Jr, Silva e Sousa AH Jr, Campos FG, Kiss DR, Gama-Rodrigues J. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg. 2004 Oct;240(4):711-7; discussion 717-8. doi: 10.1097/01.sla.0000141194.27992.32.</citation>
    <PMID>15383798</PMID>
  </reference>
  <reference>
    <citation>Habr-Gama A, Perez RO, Nadalin W, Nahas SC, Ribeiro U Jr, Silva E Sousa AH Jr, Campos FG, Kiss DR, Gama-Rodrigues J. Long-term results of preoperative chemoradiation for distal rectal cancer correlation between final stage and survival. J Gastrointest Surg. 2005 Jan;9(1):90-9; discussion 99-101. doi: 10.1016/j.gassur.2004.10.010.</citation>
    <PMID>15623449</PMID>
  </reference>
  <reference>
    <citation>Habr-Gama A, Gama-Rodrigues J, Sao Juliao GP, Proscurshim I, Sabbagh C, Lynn PB, Perez RO. Local recurrence after complete clinical response and watch and wait in rectal cancer after neoadjuvant chemoradiation: impact of salvage therapy on local disease control. Int J Radiat Oncol Biol Phys. 2014 Mar 15;88(4):822-8. doi: 10.1016/j.ijrobp.2013.12.012. Epub 2014 Feb 1.</citation>
    <PMID>24495589</PMID>
  </reference>
  <reference>
    <citation>Habr-Gama A, de Souza PM, Ribeiro U Jr, Nadalin W, Gansl R, Sousa AH Jr, Campos FG, Gama-Rodrigues J. Low rectal cancer: impact of radiation and chemotherapy on surgical treatment. Dis Colon Rectum. 1998 Sep;41(9):1087-96. doi: 10.1007/BF02239429.</citation>
    <PMID>9749491</PMID>
  </reference>
  <reference>
    <citation>Habr-Gama A. Assessment and management of the complete clinical response of rectal cancer to chemoradiotherapy. Colorectal Dis. 2006 Sep;8 Suppl 3:21-4. doi: 10.1111/j.1463-1318.2006.01066.x.</citation>
    <PMID>16813588</PMID>
  </reference>
  <reference>
    <citation>Dalton RS, Velineni R, Osborne ME, Thomas R, Harries S, Gee AS, Daniels IR. A single-centre experience of chemoradiotherapy for rectal cancer: is there potential for nonoperative management? Colorectal Dis. 2012 May;14(5):567-71. doi: 10.1111/j.1463-1318.2011.02752.x.</citation>
    <PMID>21831177</PMID>
  </reference>
  <reference>
    <citation>Maas M, Beets-Tan RG, Lambregts DM, Lammering G, Nelemans PJ, Engelen SM, van Dam RM, Jansen RL, Sosef M, Leijtens JW, Hulsewe KW, Buijsen J, Beets GL. Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol. 2011 Dec 10;29(35):4633-40. doi: 10.1200/JCO.2011.37.7176. Epub 2011 Nov 7.</citation>
    <PMID>22067400</PMID>
  </reference>
  <reference>
    <citation>Glynne-Jones R, Hughes R. Critical appraisal of the 'wait and see' approach in rectal cancer for clinical complete responders after chemoradiation. Br J Surg. 2012 Jul;99(7):897-909. doi: 10.1002/bjs.8732. Epub 2012 Apr 27.</citation>
    <PMID>22539154</PMID>
  </reference>
  <reference>
    <citation>Jorge JM, Wexner SD. Etiology and management of fecal incontinence. Dis Colon Rectum. 1993 Jan;36(1):77-97. doi: 10.1007/BF02050307.</citation>
    <PMID>8416784</PMID>
  </reference>
  <reference>
    <citation>Temple LK, Bacik J, Savatta SG, Gottesman L, Paty PB, Weiser MR, Guillem JG, Minsky BD, Kalman M, Thaler HT, Schrag D, Wong WD. The development of a validated instrument to evaluate bowel function after sphincter-preserving surgery for rectal cancer. Dis Colon Rectum. 2005 Jul;48(7):1353-65. doi: 10.1007/s10350-004-0942-z.</citation>
    <PMID>15868235</PMID>
  </reference>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>December 14, 2016</study_first_submitted>
  <study_first_submitted_qc>December 20, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 23, 2016</study_first_posted>
  <last_update_submitted>September 8, 2022</last_update_submitted>
  <last_update_submitted_qc>September 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 10, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>McGill University Health Centre/Research Institute of the McGill University Health Centre</investigator_affiliation>
    <investigator_full_name>Neil Kopek</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>Colorectal 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/NCT03001362
org study id: 14-407 GEN
nct id: NCT03001362
lead sponsor: 
has dmc: No
Patients with histologically proven adenocarcinoma of the rectum will receive pelvic
      radiotherapy to a dose of 45Gy in 25 fractions with a tumor boost to a dose of 9Gy in 5
      fractions (thus total of 54Gy/30Fx to the primary tumor), combined with radio sensitizing
      chemotherapy. Patients will then be closely monitored, through endoscopy and imaging, for
      response to treatment and relapse. Salvage oncologic surgery to be offered if there is
      failure to achieve complete clinical response or in the event of a loco regional relapse.
The combination of preoperative (chemo)radiotherapy and total mesorectal excision (TME) has
      been shown to reduce the risk of local recurrence in patients with resectable adenocarcinoma
      of the rectum. The improved local control rates come at the price of an increased risk of
      surgical complications, including a postoperative death rate of 2-8 percent which may reach
      30 per cent at 6 months in those aged over 85 years, as well as long-term impact on
      anorectal, urinary and sexual function. Patients with cancers in the low rectum in close
      proximity to the sphincter muscles, may require a permanent stoma, which can be associated
      with high psychological morbidity.

      Preoperative chemoradiotherapy followed by a delay to resection can produce pathological
      complete responses. One review of phase II and III studies identified an overall pCR rate of
      13.5%, but even higher rates of pCR have been observed with doses of radiotherapy exceeding
      45 Gy . Certainly patients who proceed to radical surgery after achieving a pCR with chemo
      radiation do have favorable long-term outcomes. But do patients whose tumor has already been
      sterilized by chemo radiotherapy need to proceed with radical surgery?

      A number of studies have now emerged highlighting the rationale of a 'wait and see' policy
      for patients who achieve a complete clinical response (cCR) after chemo radiotherapy. The
      majority of the clinical data supporting this approach have come from Brazil. The Brazilian
      data suggests that observation of such patients yields survival rates similar to those of
      patients who undergo radical surgery with confirmation of pCR. More recent studies from the
      United Kingdom and the Netherlands appear to support the feasibility of this approach. To
      date there is no published prospectively collected data of a wait-and-see policy from a North
      American Centre.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Feasibility of a "wait and see" approach
time frame: One year
description: Rate of failure to achieve CR or the rate of recurrence after achieving CR
arm group label: Radical External Beam RT for Colorectal Ca
arm group type: Experimental
description: A single arm consisting of: Radical external beam RT dose of 54 Gy in 30fx with radiosensitizing chemotherapy as per institutional standard
intervention type: Radiation
intervention name: Radical external beam radiotherapy
description: pelvic radiotherapy to a dose of 45 Gy in 25 fractions with a tumor boost to a dose of 9 Gy in 5 fractions (thus total of 54 Gy/30 fractions to the primary tumor), combined with radio sensitizing chemotherapy.
arm group label: Radical External Beam RT for Colorectal Ca
other name: Radiosensitizing chemotherapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: Neil Kopek, M.D.
role: Principal Investigator
affiliation: Radiation Oncologist
last name: Neil Kopek, M.D.
phone: 514-934-4440
email: neil.kopek@muhc.mcgill.ca
last name: Marianna Perna, CCRP,CCRC
phone: 514-934-1934
phone ext: 43191
email: marianna.perna@muhc.mcgill.ca
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Canada
citation: Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Ollier JC; EORTC Radiotherapy Group Trial 22921. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006 Sep 14;355(11):1114-23. doi: 10.1056/NEJMoa060829. Erratum In: N Engl J Med. 2007 Aug 16;357(7):728.
PMID: 16971718
citation: Gerard JP, Conroy T, Bonnetain F, Bouche O, Chapet O, Closon-Dejardin MT, Untereiner M, Leduc B, Francois E, Maurel J, Seitz JF, Buecher B, Mackiewicz R, Ducreux M, Bedenne L. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006 Oct 1;24(28):4620-5. doi: 10.1200/JCO.2006.06.7629.
PMID: 17008704
citation: Peeters KC, Marijnen CA, Nagtegaal ID, Kranenbarg EK, Putter H, Wiggers T, Rutten H, Pahlman L, Glimelius B, Leer JW, van de Velde CJ; Dutch Colorectal Cancer Group. The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma. Ann Surg. 2007 Nov;246(5):693-701. doi: 10.1097/01.sla.0000257358.56863.ce.
PMID: 17968156
citation: Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R; German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004 Oct 21;351(17):1731-40. doi: 10.1056/NEJMoa040694.
PMID: 15496622
citation: Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, Quirke P, Couture J, de Metz C, Myint AS, Bessell E, Griffiths G, Thompson LC, Parmar M. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009 Mar 7;373(9666):811-20. doi: 10.1016/S0140-6736(09)60484-0.
PMID: 19269519
citation: van Gijn W, Marijnen CA, Nagtegaal ID, Kranenbarg EM, Putter H, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van de Velde CJ; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol. 2011 Jun;12(6):575-82. doi: 10.1016/S1470-2045(11)70097-3. Epub 2011 May 17.
PMID: 21596621
citation: Borowski DW, Bradburn DM, Mills SJ, Bharathan B, Wilson RG, Ratcliffe AA, Kelly SB; Northern Region Colorectal Cancer Audit Group (NORCCAG). Volume-outcome analysis of colorectal cancer-related outcomes. Br J Surg. 2010 Sep;97(9):1416-30. doi: 10.1002/bjs.7111.
PMID: 20632311
citation: Paun BC, Cassie S, MacLean AR, Dixon E, Buie WD. Postoperative complications following surgery for rectal cancer. Ann Surg. 2010 May;251(5):807-18. doi: 10.1097/SLA.0b013e3181dae4ed.
PMID: 20395841
citation: Rutten HJ, den Dulk M, Lemmens VE, van de Velde CJ, Marijnen CA. Controversies of total mesorectal excision for rectal cancer in elderly patients. Lancet Oncol. 2008 May;9(5):494-501. doi: 10.1016/S1470-2045(08)70129-3.
PMID: 18452860
citation: Bujko K, Nowacki MP, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Kryj M. Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg. 2006 Oct;93(10):1215-23. doi: 10.1002/bjs.5506.
PMID: 16983741
citation: Gervaz PA, Wexner SD, Pemberton JH. Pelvic radiation and anorectal function: introducing the concept of sphincter-preserving radiation therapy. J Am Coll Surg. 2002 Sep;195(3):387-94. doi: 10.1016/s1072-7515(02)01308-x. No abstract available.
PMID: 12229948
citation: Hartley A, Ho KF, McConkey C, Geh JI. Pathological complete response following pre-operative chemoradiotherapy in rectal cancer: analysis of phase II/III trials. Br J Radiol. 2005 Oct;78(934):934-8. doi: 10.1259/bjr/86650067.
PMID: 16177017
citation: Maas M, Nelemans PJ, Valentini V, Das P, Rodel C, Kuo LJ, Calvo FA, Garcia-Aguilar J, Glynne-Jones R, Haustermans K, Mohiuddin M, Pucciarelli S, Small W Jr, Suarez J, Theodoropoulos G, Biondo S, Beets-Tan RG, Beets GL. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010 Sep;11(9):835-44. doi: 10.1016/S1470-2045(10)70172-8. Epub 2010 Aug 6.
PMID: 20692872
citation: Habr-Gama A, Perez RO, Proscurshim I, Campos FG, Nadalin W, Kiss D, Gama-Rodrigues J. Patterns of failure and survival for nonoperative treatment of stage c0 distal rectal cancer following neoadjuvant chemoradiation therapy. J Gastrointest Surg. 2006 Dec;10(10):1319-28; discussion 1328-9. doi: 10.1016/j.gassur.2006.09.005.
PMID: 17175450
citation: Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro U Jr, Silva e Sousa AH Jr, Campos FG, Kiss DR, Gama-Rodrigues J. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg. 2004 Oct;240(4):711-7; discussion 717-8. doi: 10.1097/01.sla.0000141194.27992.32.
PMID: 15383798
citation: Habr-Gama A, Perez RO, Nadalin W, Nahas SC, Ribeiro U Jr, Silva E Sousa AH Jr, Campos FG, Kiss DR, Gama-Rodrigues J. Long-term results of preoperative chemoradiation for distal rectal cancer correlation between final stage and survival. J Gastrointest Surg. 2005 Jan;9(1):90-9; discussion 99-101. doi: 10.1016/j.gassur.2004.10.010.
PMID: 15623449
citation: Habr-Gama A, Gama-Rodrigues J, Sao Juliao GP, Proscurshim I, Sabbagh C, Lynn PB, Perez RO. Local recurrence after complete clinical response and watch and wait in rectal cancer after neoadjuvant chemoradiation: impact of salvage therapy on local disease control. Int J Radiat Oncol Biol Phys. 2014 Mar 15;88(4):822-8. doi: 10.1016/j.ijrobp.2013.12.012. Epub 2014 Feb 1.
PMID: 24495589
citation: Habr-Gama A, de Souza PM, Ribeiro U Jr, Nadalin W, Gansl R, Sousa AH Jr, Campos FG, Gama-Rodrigues J. Low rectal cancer: impact of radiation and chemotherapy on surgical treatment. Dis Colon Rectum. 1998 Sep;41(9):1087-96. doi: 10.1007/BF02239429.
PMID: 9749491
citation: Habr-Gama A. Assessment and management of the complete clinical response of rectal cancer to chemoradiotherapy. Colorectal Dis. 2006 Sep;8 Suppl 3:21-4. doi: 10.1111/j.1463-1318.2006.01066.x.
PMID: 16813588
citation: Dalton RS, Velineni R, Osborne ME, Thomas R, Harries S, Gee AS, Daniels IR. A single-centre experience of chemoradiotherapy for rectal cancer: is there potential for nonoperative management? Colorectal Dis. 2012 May;14(5):567-71. doi: 10.1111/j.1463-1318.2011.02752.x.
PMID: 21831177
citation: Maas M, Beets-Tan RG, Lambregts DM, Lammering G, Nelemans PJ, Engelen SM, van Dam RM, Jansen RL, Sosef M, Leijtens JW, Hulsewe KW, Buijsen J, Beets GL. Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol. 2011 Dec 10;29(35):4633-40. doi: 10.1200/JCO.2011.37.7176. Epub 2011 Nov 7.
PMID: 22067400
citation: Glynne-Jones R, Hughes R. Critical appraisal of the 'wait and see' approach in rectal cancer for clinical complete responders after chemoradiation. Br J Surg. 2012 Jul;99(7):897-909. doi: 10.1002/bjs.8732. Epub 2012 Apr 27.
PMID: 22539154
citation: Jorge JM, Wexner SD. Etiology and management of fecal incontinence. Dis Colon Rectum. 1993 Jan;36(1):77-97. doi: 10.1007/BF02050307.
PMID: 8416784
citation: Temple LK, Bacik J, Savatta SG, Gottesman L, Paty PB, Weiser MR, Guillem JG, Minsky BD, Kalman M, Thaler HT, Schrag D, Wong WD. The development of a validated instrument to evaluate bowel function after sphincter-preserving surgery for rectal cancer. Dis Colon Rectum. 2005 Jul;48(7):1353-65. doi: 10.1007/s10350-004-0942-z.
PMID: 15868235
responsible party type: Principal Investigator
investigator affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
investigator full name: Neil Kopek
investigator title: Principal Investigator
mesh term: Colorectal Neoplasms
sharing ipd: No