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/NCT06017583</url>
    </required_header>
    <id_info>
      <org_study_id>2023-S845-01</org_study_id>
      <nct_id>NCT06017583</nct_id>
    </id_info>
    <brief_title>Neoadjuvant Chemotherapy With PD-1 Inhibitors Combined With SIB-IMRT in the Treatment of Locally Advanced Rectal Cancer</brief_title>
    <official_title>Neoadjuvant Chemotherapy With PD-1 Inhibitors Combined With Simultaneous Integrated Boost Intensity-modulated Radiotherapy in the Treatment of Locally Advanced Rectal Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Yong Zhang,MD</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>First Affiliated Hospital of Guangxi Medical University</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>
        This study aims to evaluate the efficacy and safety of tislelizumab combined with&#xD;
        simultaneous integrated boost intensity-modulated radiotherapy in treating locally advanced&#xD;
        rectal cancer. To explore a new PD-1 inhibitor adjuvant chemotherapy model combined with&#xD;
        radiotherapy to treat locally advanced rectal cancer.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a randomized controlled trial (RCT). Patients with T3-4 in the 8th AJCC stage or&#xD;
        positive regional lymph nodes and no distant metastases will be enrolled. Forty-eight&#xD;
        patients will be enrolled by inclusion and exclusion criteria. The enrolled patients will be&#xD;
        randomly divided into experimental and control groups (twenty-four patients for each group)&#xD;
        to receive preoperative neoadjuvant therapy. The experimental group will receive concurrent&#xD;
        simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) and concurrent&#xD;
        capecitabine chemotherapy, and complete 2 ~ 4 cycles of XELOX chemotherapy, while receiving&#xD;
        complete tislelizumab treatment for at least 4 cycles (21 days per cycle). The control group&#xD;
        received intensity-modulated radiotherapy (IMRT) without tirellizumab, and the other&#xD;
        treatment regiments were consistent with the experimental group. The tumor size will be&#xD;
        measured in MRI or CT images, and side effects will be recorded. The primary outcome was CR&#xD;
        rate (pathological complete response rate and clinical complete response rate), and secondary&#xD;
        outcomes were side effects and 3-year OS and DFS.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">August 31, 2026</completion_date>
    <primary_completion_date type="Anticipated">August 31, 2024</primary_completion_date>
    <phase>Phase 3</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>The random number table method.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Complete response rate</measure>
      <time_frame>12 weeks~18 weeks</time_frame>
      <description>Include in pathological complete response rate and clinical complete response rate. MRI/CT will be used for evaluating the carcinoma status. Pathological complete response rate will be evaluated by surgery.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Side effects</measure>
      <time_frame>6monthes, 3years</time_frame>
      <description>Myelosuppression, radiation enteritis, radiothermitis</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival</measure>
      <time_frame>3 years</time_frame>
      <description>OS was calculated from the date of entry into the study to the date of death or the last follow-up visit.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease free survival</measure>
      <time_frame>3 years</time_frame>
      <description>DFS was calculated from the date of entry into the study to the date of the time from the beginning of randomization to the disease recurrence or progression or death from any cause.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">48</enrollment>
    <condition>Rectal Neoplasms</condition>
    <arm_group>
      <arm_group_label>Experimental arm</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The experimental group will receive concurrent simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) and concurrent capecitabine chemotherapy, and complete 2 ~ 4 cycles of XELOX chemotherapy, while receiving full tislelizumab treatment for at least 4 cycles (21 days per cycle).</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control arm</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>The control group received intensity-modulated radiotherapy (IMRT) without tirellizumab, and the other treatment regiments were consistent with the experimental group.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Tislelizumab</intervention_name>
      <description>Tirellizumab was administered intravenously at 200mg/d1, 21 days per cycle, with at least 4 cycles completed.</description>
      <arm_group_label>Experimental arm</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Capecitabine</intervention_name>
      <description>Oral capecitabine 825mg/m2 bid, radiotherapy day concurrent chemotherapy. Chemotherapy regimen after radiotherapy: XELOX regimen: oxaliplatin intravenous infusion of 130mg/m2/d1+ oral capecitabine 1000mg/m2 bid/ d1-14, 21 days per cycle, at least 2 cycles completed.</description>
      <arm_group_label>Control arm</arm_group_label>
      <arm_group_label>Experimental arm</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Oxaliplatin</intervention_name>
      <description>Chemotherapy regimen after radiotherapy: XELOX regimen: oxaliplatin intravenous infusion of 130mg/m2/d1+ oral capecitabine 1000mg/m2 bid/ d1-14, 21 days per cycle, at least 2 cycles completed.</description>
      <arm_group_label>Control arm</arm_group_label>
      <arm_group_label>Experimental arm</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>SIB-IMRT</intervention_name>
      <description>The tumor and the related mesenteric region 1cm above and below were simultaneously integrated boost to 5600cGy with the intensity-modulated radiotherapy. The other dose for clinical target volume is 5000 cGy.</description>
      <arm_group_label>Experimental arm</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>IMRT</intervention_name>
      <description>The whole dose of the clinical target volume is 5000 cGy with intensity-modulated radiotherapy.</description>
      <arm_group_label>Control arm</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Aged 18 to 70 years.&#xD;
  &#xD;
            2. The pathological type of rectal cancer diagnosed by histopathology is adenocarcinoma.&#xD;
  &#xD;
            3. Patients with T3-4 in the eighth AJCC stage or positive regional lymph node and no&#xD;
               distant metastasis.&#xD;
  &#xD;
            4. Having at least one measurable lesion according to RECIST 1.1.&#xD;
  &#xD;
            5. ECOG score 0-1.&#xD;
  &#xD;
            6. Expected survival time ≥6 months.&#xD;
  &#xD;
            7. Major organ function is normal, that is, meeting the following criteria: blood&#xD;
               routine: HB≥90g/L, ANC≥1.5×109/L, PLT≥80×109/L; Biochemical examination of ALB≥30g/L,&#xD;
               TBIL≤1.5 ULN, ALT and AST≤2.5 ULN, plasma Cr≤1.5 ULN or creatinine clearance ≥60&#xD;
               ml/min.&#xD;
  &#xD;
            8. Subjects volunteered to join the study, signed the informed consent, had good&#xD;
               compliance, and cooperated with follow-up.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Patients have had or currently have other malignant tumors within 5 years.&#xD;
  &#xD;
            2. Patients allergic or sensitive to any drug in the study protocol.&#xD;
  &#xD;
            3. Patients innate or acquired immune deficiency (e.g. HIV infection).&#xD;
  &#xD;
            4. The presence of any active, known or suspected autoimmune disease (such as, but not&#xD;
               limited to, interstitial pneumonia, uveitis, enteritis, hepatitis, arthritis,&#xD;
               nephritis, hypophysitis, hyperthyroidism, hypothyroidism, etc.); The subject had&#xD;
               vitiligo. Subjects with asthma require bronchodilators for medical intervention.&#xD;
  &#xD;
            5. The presence of active infections requiring systemic treatment.&#xD;
  &#xD;
            6. The subject has previously received other PD-1 or PD-L1, or CTLA-4 antibody therapy,&#xD;
               or other drug therapy targeting immunoregulatory receptor preparations.&#xD;
  &#xD;
            7. Unrelieved toxic effects above CTCAE grade 1 due to any previous treatment, excluding&#xD;
               alopecia.&#xD;
  &#xD;
            8. Patients with a history of myocardial infarction or stroke, unstable angina pectoris,&#xD;
               decompensated heart failure or deep vein thrombosis.&#xD;
  &#xD;
            9. Patients with long-term untreated wounds or fractures, major surgical operations or&#xD;
               severe traumatic injuries, fractures or ulcers within 4 weeks.&#xD;
  &#xD;
           10. Pregnant or lactating women.&#xD;
  &#xD;
           11. Patients with liver and kidney dysfunction.&#xD;
  &#xD;
           12. Patients with a history of abuse of psychotropic drugs and unable to abstain or&#xD;
               patients with mental disorders.&#xD;
  &#xD;
           13. Patients who have participated in clinical trials of other drugs within 4 weeks.&#xD;
  &#xD;
           14. Patients with concomitant diseases that, in the judgment of the investigator,&#xD;
               seriously endanger the patient's safety or affect the patient's completion of the&#xD;
               study.&#xD;
  &#xD;
           15. The investigator judged that participation in this study was not conducive to the&#xD;
               maximum benefit of the subjects.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>70 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>First Affiliated Hospital of Guangxi Medical University</name>
        <address>
          <city>Nanning</city>
          <state>Guangxi</state>
          <zip>530021</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Yong Zhang, PhD</last_name>
        <phone>13607884001</phone>
        <email>zhangyonggx@163.com</email>
      </contact>
      <contact_backup>
        <last_name>Shanshan Ma, PhD</last_name>
        <phone>13557994302</phone>
        <email>mashanshan@gxmu.edu.cn</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 18, 2023</study_first_submitted>
    <study_first_submitted_qc>August 27, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 30, 2023</study_first_posted>
    <last_update_submitted>August 27, 2023</last_update_submitted>
    <last_update_submitted_qc>August 27, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 30, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>First Affiliated Hospital of Guangxi Medical University</investigator_affiliation>
      <investigator_full_name>Yong Zhang,MD</investigator_full_name>
      <investigator_title>First Affiliated Hospital of Guangxi Medical University</investigator_title>
    </responsible_party>
    <keyword>Rectal cancer</keyword>
    <keyword>Tislelizumab</keyword>
    <keyword>SIB IMRT</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>Capecitabine</mesh_term>
      <mesh_term>Oxaliplatin</mesh_term>
      <mesh_term>Tislelizumab</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- 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/NCT06017583
  org study id: 2023-S845-01
  nct id: NCT06017583
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This study aims to evaluate the efficacy and safety of tislelizumab combined with
        simultaneous integrated boost intensity-modulated radiotherapy in treating locally advanced
        rectal cancer. To explore a new PD-1 inhibitor adjuvant chemotherapy model combined with
        radiotherapy to treat locally advanced rectal cancer.
  This is a randomized controlled trial (RCT). Patients with T3-4 in the 8th AJCC stage or
        positive regional lymph nodes and no distant metastases will be enrolled. Forty-eight
        patients will be enrolled by inclusion and exclusion criteria. The enrolled patients will be
        randomly divided into experimental and control groups (twenty-four patients for each group)
        to receive preoperative neoadjuvant therapy. The experimental group will receive concurrent
        simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) and concurrent
        capecitabine chemotherapy, and complete 2 ~ 4 cycles of XELOX chemotherapy, while receiving
        complete tislelizumab treatment for at least 4 cycles (21 days per cycle). The control group
        received intensity-modulated radiotherapy (IMRT) without tirellizumab, and the other
        treatment regiments were consistent with the experimental group. The tumor size will be
        measured in MRI or CT images, and side effects will be recorded. The primary outcome was CR
        rate (pathological complete response rate and clinical complete response rate), and secondary
        outcomes were side effects and 3-year OS and DFS.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: The random number table method.
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Complete response rate
  time frame: 12 weeks~18 weeks
  description: Include in pathological complete response rate and clinical complete response rate. MRI/CT will be used for evaluating the carcinoma status. Pathological complete response rate will be evaluated by surgery.
  measure: Side effects
  time frame: 6monthes, 3years
  description: Myelosuppression, radiation enteritis, radiothermitis
  measure: Overall survival
  time frame: 3 years
  description: OS was calculated from the date of entry into the study to the date of death or the last follow-up visit.
  measure: Disease free survival
  time frame: 3 years
  description: DFS was calculated from the date of entry into the study to the date of the time from the beginning of randomization to the disease recurrence or progression or death from any cause.
  arm group label: Experimental arm
  arm group type: Experimental
  description: The experimental group will receive concurrent simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) and concurrent capecitabine chemotherapy, and complete 2 ~ 4 cycles of XELOX chemotherapy, while receiving full tislelizumab treatment for at least 4 cycles (21 days per cycle).
  arm group label: Control arm
  arm group type: Placebo Comparator
  description: The control group received intensity-modulated radiotherapy (IMRT) without tirellizumab, and the other treatment regiments were consistent with the experimental group.
  intervention type: Drug
  intervention name: Tislelizumab
  description: Tirellizumab was administered intravenously at 200mg/d1, 21 days per cycle, with at least 4 cycles completed.
  arm group label: Experimental arm
  intervention type: Drug
  intervention name: Capecitabine
  description: Oral capecitabine 825mg/m2 bid, radiotherapy day concurrent chemotherapy. Chemotherapy regimen after radiotherapy: XELOX regimen: oxaliplatin intravenous infusion of 130mg/m2/d1+ oral capecitabine 1000mg/m2 bid/ d1-14, 21 days per cycle, at least 2 cycles completed.
  arm group label: Control arm
  arm group label: Experimental arm
  intervention type: Drug
  intervention name: Oxaliplatin
  description: Chemotherapy regimen after radiotherapy: XELOX regimen: oxaliplatin intravenous infusion of 130mg/m2/d1+ oral capecitabine 1000mg/m2 bid/ d1-14, 21 days per cycle, at least 2 cycles completed.
  arm group label: Control arm
  arm group label: Experimental arm
  intervention type: Radiation
  intervention name: SIB-IMRT
  description: The tumor and the related mesenteric region 1cm above and below were simultaneously integrated boost to 5600cGy with the intensity-modulated radiotherapy. The other dose for clinical target volume is 5000 cGy.
  arm group label: Experimental arm
  intervention type: Radiation
  intervention name: IMRT
  description: The whole dose of the clinical target volume is 5000 cGy with intensity-modulated radiotherapy.
  arm group label: Control arm
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 70 Years
  healthy volunteers: No
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  country: China
  responsible party type: Sponsor-Investigator
  investigator affiliation: First Affiliated Hospital of Guangxi Medical University
  investigator full name: Yong Zhang,MD
  investigator title: First Affiliated Hospital of Guangxi Medical University
  mesh term: Rectal Neoplasms
  mesh term: Capecitabine
  mesh term: Oxaliplatin
  mesh term: Tislelizumab
  sharing ipd: No