<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/NCT02992886</url>
  </required_header>
  <id_info>
    <org_study_id>CH-GI-098</org_study_id>
    <nct_id>NCT02992886</nct_id>
  </id_info>
  <brief_title>Preoperative Chemoradiotherapy With Raltitrexed for Intermediate or Locally Advanced Rectal Cancer in the Fit Elderly</brief_title>
  <official_title>Multicenter, Phase II Study of Preoperative Chemoradiotherapy With Raltitrexed for Intermediate or Locally Advanced Rectal Cancer in the Fit Elderly</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this multicenter phase II study is to evaluate the response rate, local control,&#xD;
      disease-free survival and treatment-related toxicity of preoperative chemoradiation for&#xD;
      intermediate or locally advanced rectal cancer in the fit elderly.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The concurrent chemoradiotherapy has become the standard treatment for patients with&#xD;
      intermediate or locally advanced rectal cancer. However, the data from prospective trial for&#xD;
      elderly patients is still lacking.&#xD;
&#xD;
      The aim of this multicenter phase II study is to evaluate the response rate, local control,&#xD;
      disease-free survival and treatment-related toxicity of preoperative chemoradiation with&#xD;
      Raltitrexed for intermediate or locally advanced rectal cancer in the fit elderly aged 70&#xD;
      years above.&#xD;
&#xD;
      And all the participants have to be evaluated by comprehensive geriatric assessment (CGA).&#xD;
      Clinical stage was evaluated by chest and abdominal computed tomography, endorectal&#xD;
      ultrasound, and/or pelvic magnetic resonance imaging.&#xD;
&#xD;
      5 weeks after the preCRT, the multi-disciplinary team decided the following treatment of&#xD;
      patients based on imaging evaluation. Surgical resection would be done with a minimum&#xD;
      interval of 6 weeks after the last radiation. Acute toxicity was evaluated during and within&#xD;
      2 weeks after CRT. Toxicities were assessed according to the National Cancer Institute Common&#xD;
      Terminology Criteria for Adverse Events, version 4.0.&#xD;
&#xD;
      Sample size consideration.It has been calculated that 68 patients will need to be included,&#xD;
      according to the following assumptions:&#xD;
&#xD;
      Recruitment period of 24 months. Minimum follow-up period of 24 months. We estimated that 51&#xD;
      patients were required to test the hypothesis that the 2-year DFS was equal to or greater&#xD;
      than 78% with 80% power and to reject the hypothesis that the 2-year DFS rate was less than&#xD;
      63% at a significance level of 5% (one sided).Taking into account that a 5% percentage of&#xD;
      losses, 20% of patients will refuse surgery, 68 patients are expected to be included in the&#xD;
      study.&#xD;
&#xD;
      The interim analysis design. An interim safety evaluation will be carried out when 39&#xD;
      patients have finished their preoperative CRT. As the tolerance of elderly patients for&#xD;
      nonhematological toxicities (such as diarrhoea) was often more poor than hematological&#xD;
      toxicities, we estimated that 39 patients were required to test the hypothesis that the&#xD;
      nonhematological G3 or higher acute toxicities rate was equal to or less than 21% ( safety&#xD;
      result of patients aged 70 years or older from ACCOR12/PRODIGE 2 phase III trial) with 80%&#xD;
      power and to reject the hypothesis that the rate was more than 36% at a significance level of&#xD;
      10% (one sided). If nonhematological G3 or higher acute toxicites is observed in12 or more&#xD;
      patients, the H0 hypothesis will be rejected, and the protocal should be re-evaluated.&#xD;
&#xD;
      Biospecimen Retention. Blood, plasma, feces and tissue (optional). Feces were collected&#xD;
      before any treatment. Peripheral blood samples of 10-20mL were collected from the patients&#xD;
      for CTCs analysis, exploration analysis for frailty and tumor marker before and after preCRT,&#xD;
      before and after surgery, and then on each follow up visit, according to our study protocal.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2016</start_date>
  <completion_date type="Actual">August 2021</completion_date>
  <primary_completion_date type="Actual">May 2021</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>2-year disease-free survival probability (%)</measure>
    <time_frame>2 year</time_frame>
    <description>The probability of staying free from recurrence at 2 year after surgery or clinical complete response of tumor validated on imaging or pathological examination.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>5-year overall survival probability</measure>
    <time_frame>5 year</time_frame>
    <description>The probability of staying alive at 5 year after surgery or end of CRT (for those who did not receive surgery).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>5-year cancer-specific survival probability</measure>
    <time_frame>5 year</time_frame>
    <description>The probability of staying free from death caused by cancer at 5 year after surgery or end of CRT (for those who did not receive surgery).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The ratio of patients occured pCR</measure>
    <time_frame>2 weeks after surgery</time_frame>
    <description>The ratio of patients occured pathological complete response of tumor.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The ratio of patients occured Grade 3 or higher adverse events.</measure>
    <time_frame>During chemoradiotherapy and within 180 days after surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>QOL</measure>
    <time_frame>Before and after chemoradiotherapy and surgery, and then follow up for 3 years</time_frame>
    <description>The quality of life assessment score by EORTC QLQ-C30 and EORTC QLQ-CR29.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Exploratory endpoints</measure>
    <time_frame>5 years</time_frame>
    <description>To investigate the biomarker from blood or feces (such as circulating tumor cells, circulating tumor DNA) for treatment response and prognosis predicting. To investigate the CGA elements, and willingness evaluation to surgery for predicting the adherence, tolerence and prognosis of patients.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">68</enrollment>
  <condition>Rectal Neoplasms Malignant</condition>
  <arm_group>
    <arm_group_label>preCRT+surgery</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment including preoperative chemoradiotherapy (preoperative radiation with concurrent chemotherapy) with Raltitrexed followed by surgery. Radiotherapy will be delivered to a planning target volume with a dose of 45-50.4Gy (1.8-2.0Gy daily) using with Intensity-Modulated Radiotherapy or Volumetric-Modulated Arc Therapy technique. During the radiation treatment, concurrent chemotherapy will be delivered (Raltitrexed, intravenous infusion, 3 mg/m2, on d1 and d22). Pelvic surgery is planned 6 weeks after completion of CRT based on the decision of MDT.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Preoperative radiation</intervention_name>
    <description>Radiation treatment before surgery</description>
    <arm_group_label>preCRT+surgery</arm_group_label>
    <other_name>Preoperative radiotherapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Raltitrexed</intervention_name>
    <description>concurrent chemotherapy</description>
    <arm_group_label>preCRT+surgery</arm_group_label>
    <other_name>Raltitrexed Injection</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Pelvic surgery</intervention_name>
    <arm_group_label>preCRT+surgery</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  Inclusion Criteria:&#xD;
&#xD;
               -  Rectal adenocarcinoma, clinical stage II/III(T3-4 or N+, AJCC 7th), and fulfils&#xD;
                  the intermediate or locally advanced risk category standard of ESMO recal cancer&#xD;
                  clinical practice guidelines 2013.&#xD;
&#xD;
               -  KPS status no less than 70; Charlson comorbidity no more than 2; Fit status&#xD;
                  evaluated by CGA.&#xD;
&#xD;
               -  Life expectancy more than 6 months.&#xD;
&#xD;
               -  Hemoglobin &gt;= 100g/L, white blood cell &gt;= 3.5*10E9/L, neutrophil &gt;= 1.5*10E9/L,&#xD;
                  platelet &gt;= 100*10E9/L.&#xD;
&#xD;
               -  Creatin normal, Total bilirubin normal, AST and AST normal, AKP normal.&#xD;
&#xD;
               -  Do not receive surgery ( except palliative colostomy) or chemotherapy or other&#xD;
                  anti-cancer treatment.&#xD;
&#xD;
               -  No previously pelvic irradiation history.&#xD;
&#xD;
               -  Through MDT discussion, the patient is considered to be candidate for&#xD;
                  preoperative CRT followed by surgery.&#xD;
&#xD;
               -  Informed consent signed.&#xD;
&#xD;
          -  Exclusion Criteria:&#xD;
&#xD;
               -  Other cancer history, except curable non-melanoma skin cancer or cervix in-situ&#xD;
                  carcinoma.&#xD;
&#xD;
               -  Allergy history to analog of quinazoline folate.&#xD;
&#xD;
               -  Active infection existed.&#xD;
&#xD;
               -  Severe complication, such as acute myocardial infarction in 6 months,&#xD;
                  uncontrolled diabetes ( Plasma glucose concentrations in any time of a&#xD;
                  day≥11.1mmol/L）, severe cardiac arrhythmia, etc.&#xD;
&#xD;
               -  Anticipate other clinical trials in four weeks before enrollment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>71 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jing Jin, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences &amp; Peking Union Medical College</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100021</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Papamichael D, Audisio RA, Glimelius B, de Gramont A, Glynne-Jones R, Haller D, Kohne CH, Rostoft S, Lemmens V, Mitry E, Rutten H, Sargent D, Sastre J, Seymour M, Starling N, Van Cutsem E, Aapro M. Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013. Ann Oncol. 2015 Mar;26(3):463-76. doi: 10.1093/annonc/mdu253. Epub 2014 Jul 11.</citation>
    <PMID>25015334</PMID>
  </reference>
  <reference>
    <citation>Li M, Gu J. Changing patterns of colorectal cancer in China over a period of 20 years. World J Gastroenterol. 2005 Aug 14;11(30):4685-8. doi: 10.3748/wjg.v11.i30.4685.</citation>
    <PMID>16094710</PMID>
  </reference>
  <reference>
    <citation>Fiorica F, Cartei F, Licata A, Enea M, Ursino S, Colosimo C, Camma C. Can chemotherapy concomitantly delivered with radiotherapy improve survival of patients with resectable rectal cancer? A meta-analysis of literature data. Cancer Treat Rev. 2010 Nov;36(7):539-49. doi: 10.1016/j.ctrv.2010.03.002. Epub 2010 Mar 23.</citation>
    <PMID>20334979</PMID>
  </reference>
  <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>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>Teoh S, Muirhead R. Rectal Radiotherapy--Intensity-modulated Radiotherapy Delivery, Delineation and Doses. Clin Oncol (R Coll Radiol). 2016 Feb;28(2):93-102. doi: 10.1016/j.clon.2015.10.012. Epub 2015 Nov 28. Erratum In: Clin Oncol (R Coll Radiol). 2016 Mar;28(3):230.</citation>
    <PMID>26643092</PMID>
  </reference>
  <reference>
    <citation>Tang Y, Liu WY, Jin J, Zhang HZ, Yang L, Ren H, Fang H, Wang WH, Song YW, Liu YP, Wang SL, Li YX. Preoperative chemoradiation with capecitabine for rectal cancer in elderly patients: a phase I trial. Int J Colorectal Dis. 2016 Aug;31(8):1547-9. doi: 10.1007/s00384-016-2577-7. Epub 2016 Apr 8. No abstract available.</citation>
    <PMID>27059037</PMID>
  </reference>
  <reference>
    <citation>Thomas RJ, Williams M, Garcia-Vargas J. Lessons learned from raltitrexed--quality assurance, patient education and intensive supportive drugs to optimise tolerability. Clin Oncol (R Coll Radiol). 2003 Aug;15(5):227-32. doi: 10.1016/s0936-6555(03)00092-x.</citation>
    <PMID>12924450</PMID>
  </reference>
  <reference>
    <citation>Cunningham D, Zalcberg J, Maroun J, James R, Clarke S, Maughan TS, Vincent M, Schulz J, Gonzalez Baron M, Facchini T. Efficacy, tolerability and management of raltitrexed (Tomudex) monotherapy in patients with advanced colorectal cancer. a review of phase II/III trials. Eur J Cancer. 2002 Mar;38(4):478-86. doi: 10.1016/s0959-8049(01)00413-0.</citation>
    <PMID>11872339</PMID>
  </reference>
  <reference>
    <citation>Feliu J, Mel JR, Camps C, Escudero P, Aparicio J, Menendez D, Garcia Giron C, Rodriguez MR, Sanchez JJ, Gonzalez Baron M; Oncopaz Cooperative Group Associated Hospitals. Raltitrexed in the treatment of elderly patients with advanced colorectal cancer: an active and low toxicity regimen. Eur J Cancer. 2002 Jun;38(9):1204-11. doi: 10.1016/s0959-8049(02)00005-9.</citation>
    <PMID>12044507</PMID>
  </reference>
  <reference>
    <citation>Valentini V, Doglietto GB, Morganti AG, Turriziani A, Smaniotto D, De Santis M, Ratto C, Sofo L, Cellini N. Preoperative chemoradiation with raltitrexed ('Tomudex') for T2/N+ and T3/N+ rectal cancers: a phase I study. Eur J Cancer. 2001 Nov;37(16):2050-5. doi: 10.1016/s0959-8049(01)00247-7.</citation>
    <PMID>11597383</PMID>
  </reference>
  <reference>
    <citation>Valentini V, Coco C, Minsky BD, Gambacorta MA, Cosimelli M, Bellavita R, Morganti AG, La Torre G, Trodella L, Genovesi D, Portaluri M, Maurizi-Enrici R, Barbera F, Maranzano E, Lupattelli M. Randomized, multicenter, phase IIb study of preoperative chemoradiotherapy in T3 mid-distal rectal cancer: raltitrexed + oxaliplatin + radiotherapy versus cisplatin + 5-fluorouracil + radiotherapy. Int J Radiat Oncol Biol Phys. 2008 Feb 1;70(2):403-12. doi: 10.1016/j.ijrobp.2007.06.025. Epub 2007 Oct 4.</citation>
    <PMID>17919844</PMID>
  </reference>
  <reference>
    <citation>Francois E, Azria D, Gourgou-Bourgade S, Jarlier M, Martel-Laffay I, Hennequin C, Etienne PL, Vendrely V, Seitz JF, Conroy T, Juzyna B, Gerard JP. Results in the elderly with locally advanced rectal cancer from the ACCOR12/PRODIGE 2 phase III trial: tolerance and efficacy. Radiother Oncol. 2014 Jan;110(1):144-9. doi: 10.1016/j.radonc.2013.10.019. Epub 2014 Jan 10.</citation>
    <PMID>24418359</PMID>
  </reference>
  <reference>
    <citation>Glimelius B, Tiret E, Cervantes A, Arnold D; ESMO Guidelines Working Group. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013 Oct;24 Suppl 6:vi81-8. doi: 10.1093/annonc/mdt240. No abstract available.</citation>
    <PMID>24078665</PMID>
  </reference>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>November 30, 2016</study_first_submitted>
  <study_first_submitted_qc>December 13, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 14, 2016</study_first_posted>
  <last_update_submitted>September 1, 2021</last_update_submitted>
  <last_update_submitted_qc>September 1, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</investigator_affiliation>
    <investigator_full_name>Jing Jin, M.D.</investigator_full_name>
    <investigator_title>Vice Chair of Radiation Oncology</investigator_title>
  </responsible_party>
  <keyword>elderly patients</keyword>
  <keyword>rectal cancer</keyword>
  <keyword>preoperative chemoradiotherapy</keyword>
  <keyword>comprehensive geriatric assessment</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rectal Neoplasms</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Raltitrexed</mesh_term>
  </intervention_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/NCT02992886
org study id: CH-GI-098
nct id: NCT02992886
lead sponsor: 
has dmc: Yes
The aim of this multicenter phase II study is to evaluate the response rate, local control,
      disease-free survival and treatment-related toxicity of preoperative chemoradiation for
      intermediate or locally advanced rectal cancer in the fit elderly.
The concurrent chemoradiotherapy has become the standard treatment for patients with
      intermediate or locally advanced rectal cancer. However, the data from prospective trial for
      elderly patients is still lacking.

      The aim of this multicenter phase II study is to evaluate the response rate, local control,
      disease-free survival and treatment-related toxicity of preoperative chemoradiation with
      Raltitrexed for intermediate or locally advanced rectal cancer in the fit elderly aged 70
      years above.

      And all the participants have to be evaluated by comprehensive geriatric assessment (CGA).
      Clinical stage was evaluated by chest and abdominal computed tomography, endorectal
      ultrasound, and/or pelvic magnetic resonance imaging.

      5 weeks after the preCRT, the multi-disciplinary team decided the following treatment of
      patients based on imaging evaluation. Surgical resection would be done with a minimum
      interval of 6 weeks after the last radiation. Acute toxicity was evaluated during and within
      2 weeks after CRT. Toxicities were assessed according to the National Cancer Institute Common
      Terminology Criteria for Adverse Events, version 4.0.

      Sample size consideration.It has been calculated that 68 patients will need to be included,
      according to the following assumptions:

      Recruitment period of 24 months. Minimum follow-up period of 24 months. We estimated that 51
      patients were required to test the hypothesis that the 2-year DFS was equal to or greater
      than 78% with 80% power and to reject the hypothesis that the 2-year DFS rate was less than
      63% at a significance level of 5% (one sided).Taking into account that a 5% percentage of
      losses, 20% of patients will refuse surgery, 68 patients are expected to be included in the
      study.

      The interim analysis design. An interim safety evaluation will be carried out when 39
      patients have finished their preoperative CRT. As the tolerance of elderly patients for
      nonhematological toxicities (such as diarrhoea) was often more poor than hematological
      toxicities, we estimated that 39 patients were required to test the hypothesis that the
      nonhematological G3 or higher acute toxicities rate was equal to or less than 21% ( safety
      result of patients aged 70 years or older from ACCOR12/PRODIGE 2 phase III trial) with 80%
      power and to reject the hypothesis that the rate was more than 36% at a significance level of
      10% (one sided). If nonhematological G3 or higher acute toxicites is observed in12 or more
      patients, the H0 hypothesis will be rejected, and the protocal should be re-evaluated.

      Biospecimen Retention. Blood, plasma, feces and tissue (optional). Feces were collected
      before any treatment. Peripheral blood samples of 10-20mL were collected from the patients
      for CTCs analysis, exploration analysis for frailty and tumor marker before and after preCRT,
      before and after surgery, and then on each follow up visit, according to our study protocal.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: 2-year disease-free survival probability (%)
time frame: 2 year
description: The probability of staying free from recurrence at 2 year after surgery or clinical complete response of tumor validated on imaging or pathological examination.
measure: 5-year overall survival probability
time frame: 5 year
description: The probability of staying alive at 5 year after surgery or end of CRT (for those who did not receive surgery).
measure: 5-year cancer-specific survival probability
time frame: 5 year
description: The probability of staying free from death caused by cancer at 5 year after surgery or end of CRT (for those who did not receive surgery).
measure: The ratio of patients occured pCR
time frame: 2 weeks after surgery
description: The ratio of patients occured pathological complete response of tumor.
measure: The ratio of patients occured Grade 3 or higher adverse events.
time frame: During chemoradiotherapy and within 180 days after surgery
measure: QOL
time frame: Before and after chemoradiotherapy and surgery, and then follow up for 3 years
description: The quality of life assessment score by EORTC QLQ-C30 and EORTC QLQ-CR29.
measure: Exploratory endpoints
time frame: 5 years
description: To investigate the biomarker from blood or feces (such as circulating tumor cells, circulating tumor DNA) for treatment response and prognosis predicting. To investigate the CGA elements, and willingness evaluation to surgery for predicting the adherence, tolerence and prognosis of patients.
arm group label: preCRT+surgery
arm group type: Experimental
description: Treatment including preoperative chemoradiotherapy (preoperative radiation with concurrent chemotherapy) with Raltitrexed followed by surgery. Radiotherapy will be delivered to a planning target volume with a dose of 45-50.4Gy (1.8-2.0Gy daily) using with Intensity-Modulated Radiotherapy or Volumetric-Modulated Arc Therapy technique. During the radiation treatment, concurrent chemotherapy will be delivered (Raltitrexed, intravenous infusion, 3 mg/m2, on d1 and d22). Pelvic surgery is planned 6 weeks after completion of CRT based on the decision of MDT.
intervention type: Radiation
intervention name: Preoperative radiation
description: Radiation treatment before surgery
arm group label: preCRT+surgery
other name: Preoperative radiotherapy
intervention type: Drug
intervention name: Raltitrexed
description: concurrent chemotherapy
arm group label: preCRT+surgery
other name: Raltitrexed Injection
intervention type: Procedure
intervention name: Pelvic surgery
arm group label: preCRT+surgery
criteria: 
gender: All
minimum age: 71 Years
maximum age: N/A
healthy volunteers: No
last name: Jing Jin, MD
role: Principal Investigator
affiliation: National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
facility: 
country: China
citation: Papamichael D, Audisio RA, Glimelius B, de Gramont A, Glynne-Jones R, Haller D, Kohne CH, Rostoft S, Lemmens V, Mitry E, Rutten H, Sargent D, Sastre J, Seymour M, Starling N, Van Cutsem E, Aapro M. Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013. Ann Oncol. 2015 Mar;26(3):463-76. doi: 10.1093/annonc/mdu253. Epub 2014 Jul 11.
PMID: 25015334
citation: Li M, Gu J. Changing patterns of colorectal cancer in China over a period of 20 years. World J Gastroenterol. 2005 Aug 14;11(30):4685-8. doi: 10.3748/wjg.v11.i30.4685.
PMID: 16094710
citation: Fiorica F, Cartei F, Licata A, Enea M, Ursino S, Colosimo C, Camma C. Can chemotherapy concomitantly delivered with radiotherapy improve survival of patients with resectable rectal cancer? A meta-analysis of literature data. Cancer Treat Rev. 2010 Nov;36(7):539-49. doi: 10.1016/j.ctrv.2010.03.002. Epub 2010 Mar 23.
PMID: 20334979
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responsible party type: Principal Investigator
investigator affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
investigator full name: Jing Jin, M.D.
investigator title: Vice Chair of Radiation Oncology
mesh term: Rectal Neoplasms
mesh term: Neoplasms
mesh term: Raltitrexed
sharing ipd: No