xml: <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/NCT05965531</url>
    </required_header>
    <id_info>
      <org_study_id>2023-FXY-087</org_study_id>
      <nct_id>NCT05965531</nct_id>
    </id_info>
    <brief_title>Treating Locally Advanced Rectal Cancer With TAS-102 Chemotherapy Plus Neoadjuvant Radiotherapy</brief_title>
    <acronym>TASLARC</acronym>
    <official_title>A Single-arm, Phase II Clinical Trial to Treat Locally Advanced, pMMR Rectal Cancer With Single-agent Trifluridine/Tipiracil Chemotherapy Plus Neoadjuvant Intensity-modulated Radiotherapy</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Sun Yat-sen University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Sun Yat-sen University</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this Phase 2 trial is to evaluate a neoadjuvant treatment mode for locally&#xD;
        advanced rectal cancer (LARC), consisting of radiotherapy and concurrent&#xD;
        Trifluridine/Tipiracil (TAS-102). The main questions it aims to answer are: (i) whether&#xD;
        TAS-102 is effective in treating LARC, when combined with radiotherapy; (ii) whether TAS-102&#xD;
        is safe in combination with radiotherapy. Participants will receive one cycle of TAS-102&#xD;
        chemotherapy and neoadjuvant radiotherapy based on intensity-modulated technique. Then the&#xD;
        ones with a possibility of R0 resection will receive radical surgery followed by 6 cycles of&#xD;
        adjuvant XELOX (capecitabine plus oxaliplatin) chemotherapy.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The standard management recommended by the National Comprehensive Cancer Network for locally&#xD;
        advanced rectal cancer (LARC) is neoadjuvant chemo-radiotherapy followed by surgery plus&#xD;
        adjuvant chemotherapy or not. Currently, the regimens of neoadjuvant chemotherapy are based&#xD;
        on fluorouracil or capecitabine. The therapeutic effects of these regimens are satisfactory,&#xD;
        with a pathological complete response (pCR) and 3-year disease-free survival (DFS) rate of&#xD;
        14% and 68%. Addition of oxaliplatin has been proven to further improve the pCR and DFS&#xD;
        rates, by the CAO/ARO/AIO-04, FOWARC and ADORE trials. However, the acute toxicities of&#xD;
        fluorouracil and capecitabine remain as a concern. It was reported that the incidence of the&#xD;
        grade 3/4 symptomatic toxicities brought by these two agents was nearly 15%. When combined&#xD;
        with oxaliplatin, the incidence could rise to 25%. A special toxicity, hand-foot syndrome,&#xD;
        was seen in 43-71% of the patients receiving capecitabine. It included blister, ulceration,&#xD;
        numbness, pain and paresthesia, and seriously influenced the daily work and life of the&#xD;
        patients. Trifluridine/Tipiracil (TAS-102) is a new generation of cytotoxic agent whose&#xD;
        therapeutic effects in metastatic colorectal cancer have been confirmed by a series of&#xD;
        large-scale, multicenter, randomized controlled trials. And the latest TASCO1 trial reported&#xD;
        that TAS-102 exhibited a trend to improve overall survival, compared to capecitabine.&#xD;
        Moreover, it could be well tolerated, with an incidence of grade 3/4 symptomatic toxicities&#xD;
        of merely 1.5%. Until now, there was few study focusing on combination of TAS-102 and&#xD;
        radiotherapy. This phase 2 trial intended to evaluate the therapeutic and adverse effects of&#xD;
        TAS-102 concurrently with neoadjuvant radiotherapy, in a small patient cohort with LARC. The&#xD;
        results might provide an effective and low-toxic choice which improves patients' experience&#xD;
        of chemo-radiotherapy.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 1, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2028</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2028</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 study adopts the Simon's optimal two-stage design and uses the objective response rate (ORR) as the primary endpoint. The first stage will enroll 19 eligible patients. If the observed ORR &gt; 70%, the study will enter the second stage and continue to enroll 40 eligible patients. The final sample size is 65 when a drop-out rate of 10% is considered.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Objective response rate</measure>
      <time_frame>One week after surgery</time_frame>
      <description>The percentage of the patients complete R0 resection and attain a tumor regression grade of 1-4 (Mandard's 5-tier standard) in postsurgical pathologic examination</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Pathological complete response rate</measure>
      <time_frame>One week after surgery</time_frame>
      <description>The percentage of the patients complete R0 resection and attain a complete remission of both primary tumor and regional lymph nodes in postsurgical pathologic examination</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The incidence of grade 3/4 toxicities</measure>
      <time_frame>Once a week during the period of neoadjuvant treatment</time_frame>
      <description>The percentage of the patients undergo any grade 3/4 toxicity during neoadjuvant treatment, based on the Common Terminology Criteria for Adverse Events</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The incidence of grade 3/4 complications</measure>
      <time_frame>The period from the date of radical surgery to the 90th day after surgery</time_frame>
      <description>The percentage of the patients undergo any grade 3/4 surgery-related complication, based on the Clavien-Dindo classification.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease-free survival</measure>
      <time_frame>When all the patients are followed-up for 1, 2 and 5 years</time_frame>
      <description>The percentage of the patients survive without local recurrence or distant metastasis after a time period, from pathological diagnosis</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival</measure>
      <time_frame>When all the patients are followed-up for 1, 2 and 5 years</time_frame>
      <description>The percentage of the patients survive after a time period, from pathological diagnosis</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">65</enrollment>
    <condition>Rectal Cancer</condition>
    <arm_group>
      <arm_group_label>Neoadjuvant chemo-radiotherapy with TAS-102</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The patients in this group will all receive neoadjuvant treatment consisting of intensity-modulated radiotherapy and concurrent Trifluridine/Tipiracil (TAS-102). Then the ones evaluated to have a possibility of R0 resection will receive radical surgery, followed by 6 cycles of adjuvant XELOX (capecitabine plus oxaliplatin) chemotherapy.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Trifluridine/Tipiracil</intervention_name>
      <description>TAS-102 is given in a dose of 35 mg/m2, twice daily on the 1st to 5th and 8th to 12th days of the period of neoadjuvant radiotherapy.</description>
      <arm_group_label>Neoadjuvant chemo-radiotherapy with TAS-102</arm_group_label>
      <other_name>TAS-102</other_name>
    </intervention>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>intensity-modulated radiotherapy</intervention_name>
      <description>intensity-modulated radiotherapy</description>
      <arm_group_label>Neoadjuvant chemo-radiotherapy with TAS-102</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Pathologically diagnosed rectal adenocarcinoma via biopsy&#xD;
  &#xD;
            -  Pretreatment clinical TNM stage as T3-4N0M0 or T1-4N1-2M0 (UICC TNM staging&#xD;
               classification, version 8)&#xD;
  &#xD;
            -  Tumor with proficient DNA mismatch repair confirmed by immunohistochemical analysis&#xD;
  &#xD;
            -  Age between 18 and 70 years old&#xD;
  &#xD;
            -  Karnofsky performance score ≥ 70&#xD;
  &#xD;
            -  Distance from tumor lower margin to anal verge &lt; 12 cm&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Inguinal lymph node metastasis&#xD;
  &#xD;
            -  Multiple primary colorectal cancer&#xD;
  &#xD;
            -  Complete obstruction or perforation&#xD;
  &#xD;
            -  Uncontrolled tuberculosis, AIDS or mental diseases&#xD;
  &#xD;
            -  Severe cardiac, renal, hepatic or hematopoietic dysfunctions unsuitable for&#xD;
               chemotherapy or radiotherapy&#xD;
  &#xD;
            -  Prior history of other malignancies with 5 years, except cured cervical carcinoma in&#xD;
               situ and skin basal cell carcinoma&#xD;
  &#xD;
            -  Prior history of rectal surgery, pelvic radiotherapy or chemotherapy&#xD;
  &#xD;
            -  Pregnant or lactating women&#xD;
  &#xD;
            -  Other situations for which the investigators consider a patient inappropriate to&#xD;
               participate&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>70 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Hui Chang, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Sun Yat-sen University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Hui Chang, MD</last_name>
      <phone>+86-020-87343374</phone>
      <email>changhui@sysucc.org.cn</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Qiao-xuan Wang, MD</last_name>
      <phone>+86-020-87343374</phone>
      <email>wangqx@sysucc.org.cn</email>
    </overall_contact_backup>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 14, 2023</study_first_submitted>
    <study_first_submitted_qc>July 27, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 28, 2023</study_first_posted>
    <last_update_submitted>July 27, 2023</last_update_submitted>
    <last_update_submitted_qc>July 27, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">July 28, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
      <investigator_full_name>Hui Chang</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <keyword>rectal cancer</keyword>
    <keyword>Trifluridine/Tipiracil</keyword>
    <keyword>radiotherapy</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Rectal Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Trifluridine</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05965531
  org study id: 2023-FXY-087
  nct id: NCT05965531
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this Phase 2 trial is to evaluate a neoadjuvant treatment mode for locally
        advanced rectal cancer (LARC), consisting of radiotherapy and concurrent
        Trifluridine/Tipiracil (TAS-102). The main questions it aims to answer are: (i) whether
        TAS-102 is effective in treating LARC, when combined with radiotherapy; (ii) whether TAS-102
        is safe in combination with radiotherapy. Participants will receive one cycle of TAS-102
        chemotherapy and neoadjuvant radiotherapy based on intensity-modulated technique. Then the
        ones with a possibility of R0 resection will receive radical surgery followed by 6 cycles of
        adjuvant XELOX (capecitabine plus oxaliplatin) chemotherapy.
  The standard management recommended by the National Comprehensive Cancer Network for locally
        advanced rectal cancer (LARC) is neoadjuvant chemo-radiotherapy followed by surgery plus
        adjuvant chemotherapy or not. Currently, the regimens of neoadjuvant chemotherapy are based
        on fluorouracil or capecitabine. The therapeutic effects of these regimens are satisfactory,
        with a pathological complete response (pCR) and 3-year disease-free survival (DFS) rate of
        14% and 68%. Addition of oxaliplatin has been proven to further improve the pCR and DFS
        rates, by the CAO/ARO/AIO-04, FOWARC and ADORE trials. However, the acute toxicities of
        fluorouracil and capecitabine remain as a concern. It was reported that the incidence of the
        grade 3/4 symptomatic toxicities brought by these two agents was nearly 15%. When combined
        with oxaliplatin, the incidence could rise to 25%. A special toxicity, hand-foot syndrome,
        was seen in 43-71% of the patients receiving capecitabine. It included blister, ulceration,
        numbness, pain and paresthesia, and seriously influenced the daily work and life of the
        patients. Trifluridine/Tipiracil (TAS-102) is a new generation of cytotoxic agent whose
        therapeutic effects in metastatic colorectal cancer have been confirmed by a series of
        large-scale, multicenter, randomized controlled trials. And the latest TASCO1 trial reported
        that TAS-102 exhibited a trend to improve overall survival, compared to capecitabine.
        Moreover, it could be well tolerated, with an incidence of grade 3/4 symptomatic toxicities
        of merely 1.5%. Until now, there was few study focusing on combination of TAS-102 and
        radiotherapy. This phase 2 trial intended to evaluate the therapeutic and adverse effects of
        TAS-102 concurrently with neoadjuvant radiotherapy, in a small patient cohort with LARC. The
        results might provide an effective and low-toxic choice which improves patients' experience
        of chemo-radiotherapy.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: This study adopts the Simon's optimal two-stage design and uses the objective response rate (ORR) as the primary endpoint. The first stage will enroll 19 eligible patients. If the observed ORR > 70%, the study will enter the second stage and continue to enroll 40 eligible patients. The final sample size is 65 when a drop-out rate of 10% is considered.
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Objective response rate
  time frame: One week after surgery
  description: The percentage of the patients complete R0 resection and attain a tumor regression grade of 1-4 (Mandard's 5-tier standard) in postsurgical pathologic examination
  measure: Pathological complete response rate
  time frame: One week after surgery
  description: The percentage of the patients complete R0 resection and attain a complete remission of both primary tumor and regional lymph nodes in postsurgical pathologic examination
  measure: The incidence of grade 3/4 toxicities
  time frame: Once a week during the period of neoadjuvant treatment
  description: The percentage of the patients undergo any grade 3/4 toxicity during neoadjuvant treatment, based on the Common Terminology Criteria for Adverse Events
  measure: The incidence of grade 3/4 complications
  time frame: The period from the date of radical surgery to the 90th day after surgery
  description: The percentage of the patients undergo any grade 3/4 surgery-related complication, based on the Clavien-Dindo classification.
  measure: Disease-free survival
  time frame: When all the patients are followed-up for 1, 2 and 5 years
  description: The percentage of the patients survive without local recurrence or distant metastasis after a time period, from pathological diagnosis
  measure: Overall survival
  time frame: When all the patients are followed-up for 1, 2 and 5 years
  description: The percentage of the patients survive after a time period, from pathological diagnosis
  arm group label: Neoadjuvant chemo-radiotherapy with TAS-102
  arm group type: Experimental
  description: The patients in this group will all receive neoadjuvant treatment consisting of intensity-modulated radiotherapy and concurrent Trifluridine/Tipiracil (TAS-102). Then the ones evaluated to have a possibility of R0 resection will receive radical surgery, followed by 6 cycles of adjuvant XELOX (capecitabine plus oxaliplatin) chemotherapy.
  intervention type: Drug
  intervention name: Trifluridine/Tipiracil
  description: TAS-102 is given in a dose of 35 mg/m2, twice daily on the 1st to 5th and 8th to 12th days of the period of neoadjuvant radiotherapy.
  arm group label: Neoadjuvant chemo-radiotherapy with TAS-102
  other name: TAS-102
  intervention type: Radiation
  intervention name: intensity-modulated radiotherapy
  description: intensity-modulated radiotherapy
  arm group label: Neoadjuvant chemo-radiotherapy with TAS-102
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 70 Years
  healthy volunteers: No
  last name: Hui Chang, MD
  role: Principal Investigator
  affiliation: Sun Yat-sen University
  last name: Hui Chang, MD
  phone: +86-020-87343374
  email: changhui@sysucc.org.cn
  last name: Qiao-xuan Wang, MD
  phone: +86-020-87343374
  email: wangqx@sysucc.org.cn
  responsible party type: Principal Investigator
  investigator affiliation: Sun Yat-sen University
  investigator full name: Hui Chang
  investigator title: Professor
  mesh term: Rectal Neoplasms
  mesh term: Trifluridine