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/NCT06024356</url>
    </required_header>
    <id_info>
      <org_study_id>BFH-TTNCRT</org_study_id>
      <nct_id>NCT06024356</nct_id>
    </id_info>
    <brief_title>Neoadjuvant Chemoradiotherapy Combined With PD-1 Inhibitor and Thymalfasin for Locally Advanced Mid-low Rectal Cancer</brief_title>
    <official_title>Efficacy and Safety of Neoadjuvant Chemoradiotherapy Combined With PD-1 Inhibitor and Thymalfasin for Locally Advanced Mid-low Rectal Cancer: a Single-center, Retrospective, Controlled Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Beijing Friendship Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Beijing Friendship Hospital</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>
        It is a single-center, retrospective, controlled study to investigate the efficacy and safety&#xD;
        of neoadjuvant chemoradiotherapy combined with PD-1 inhibitor and thymalfasin for locally&#xD;
        advanced mid-low rectal cancer.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Study Purpose&#xD;
  &#xD;
          1. To evaluate the efficacy and safety of neoadjuvant chemoradiotherapy combined with PD-1&#xD;
             inhibitor and thymalfasin for locally advanced mid-low rectal cancer.&#xD;
  &#xD;
          2. To explore the effects of neoadjuvant chemoradiotherapy combined with PD-1 inhibitor and&#xD;
             thymalfasin on the immune microenvironment of locally advanced mid-low rectal cancer.&#xD;
  &#xD;
        Study Design: A single-center, retrospective, controlled study Subjects were divided into two&#xD;
        groups according to whether or not they received thymalfasin: group 1 was treated with&#xD;
        neoadjuvant chemoradiotherapy combined with PD-1 inhibitor, and group 2 was treated with&#xD;
        neoadjuvant chemoradiotherapy combined with PD-1 inhibitor and thymalfasin.&#xD;
  &#xD;
        Subjects received long course radiotherapy (50 Gy/25f, 2 Gy/f, 5 days/week) for the first 5&#xD;
        weeks and three 21-day cycles capecitabine (1000 mg/m2, bid, po, day1-14) plus three 21-day&#xD;
        cycles tislelizumab (200 mg, iv.gtt, day 8) for the first 9 weeks. After that, patients&#xD;
        rested for two weeks (week 10-11)。6-8 weeks after the end of radiotherapy, patients underwent&#xD;
        TME surgery (12-14 weeks). Thymalfasin was started on the first day of neoadjuvant&#xD;
        chemoradiotherapy, 1.6 mg subcutaneously twice a week until the end of the last neoadjuvant&#xD;
        treatment.&#xD;
  &#xD;
        Enrollment: 26 participants, 13 in each group Study Population: locally advanced mid-low&#xD;
        rectal cancer Primary Endpoint: pathologic complete response（pCR） Exploratory endpoint:&#xD;
        Paraffin specimens were collected from biopsies before neoadjuvant therapy and after surgery&#xD;
        in patients meeting the inclusion criteria. The expression of CD86, CD163, CD4+T，CD8+T，PD-1&#xD;
        were detected.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 20, 2023</start_date>
    <completion_date type="Anticipated">March 30, 2024</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Case-Control</observational_model>
      <time_perspective>Retrospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>pathologic complete response</measure>
      <time_frame>1 year</time_frame>
      <description>All the enrolled patients will receive total mesorectal excision (TME) 7-9 weeks after the end of long course radiotherapy. The rectal specimens will be evaluated by the pathologists who are experienced on the rectal cancer diagnosis according to the 1997 Dworak grading system. The rectal cancer will be classified into 5 grades. Grade 0-3 will be considered as non-pCR while grade 4 represent pCR.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>neoadjuvant rectal (NAR) score</measure>
      <time_frame>1 year</time_frame>
      <description>The neoadjuvant rectal (NAR) score is a promising indicator of survival after preoperative chemoradiotherapy for rectal cancer. The NAR score was calculated according to the following formula: NAR score = [5pN - 3(cT - pT) + 12]2⁄9.61.&#xD;
  (clinical tumor (cT) stage, pathologic tumor (pT) stage, pathologic nodal (pN) stage)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>tumor regression grade（TRG）</measure>
      <time_frame>1 year</time_frame>
      <description>AJCC 8th TRG classification. TRG 0: No viable cancer cells left in the specimen; complete regression.&#xD;
  TRG 1: Minimal residual cancer cells present; extensive regression with a minimal number of tumor cells.&#xD;
  TRG 2: Moderate residual cancer cells present; substantial regression with a significant number of tumor cells.&#xD;
  TRG 3: Minimal or no regression; no significant tumor cell response to treatment; majority of tumor still present.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>objective response rate (ORR)</measure>
      <time_frame>1 year</time_frame>
      <description>ORR is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The ORR rate is the sum of complete response (CR) and partial response (PR)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>R0 resection rate</measure>
      <time_frame>1 year</time_frame>
      <description>During the surgical process, the surgeon will evaluate the level of cancer resection. It will be classified as R0, R1, R2 resection. Therefore, we can calculate R0 resection rate.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>anal preservation rate</measure>
      <time_frame>1 year</time_frame>
      <description>the surgeon will decide whether the anal can be preserved on the basis of the rectal cancer and intraoperative situation. anal preservation rate is the percentage of patients who achieve anal preservation.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>disease free survival (DFS)</measure>
      <time_frame>3 year</time_frame>
      <description>During the 3-year follow-up, the percentage of the patients who is disease free.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>local recurrence free survival</measure>
      <time_frame>3 year</time_frame>
      <description>During the 3-year follow-up, the percentage of local recurrence.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>overall survival (OS)</measure>
      <time_frame>3 year</time_frame>
      <description>During the 3-year follow-up, the percentage of the patients who is sill survival at the end of follow-up.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>The expression of CD86</measure>
      <time_frame>1 year</time_frame>
      <description>The density, H-score of each marker in paraffin-embedded tissue sections detected by mIHC</description>
    </other_outcome>
    <other_outcome>
      <measure>The expression of CD163</measure>
      <time_frame>1 year</time_frame>
      <description>The density, H-score of each marker in paraffin-embedded tissue sections detected by mIHC</description>
    </other_outcome>
    <other_outcome>
      <measure>The expression of CD4+</measure>
      <time_frame>1 year</time_frame>
      <description>The density, H-score of each marker in paraffin-embedded tissue sections detected by mIHC</description>
    </other_outcome>
    <other_outcome>
      <measure>The expression of CD8+</measure>
      <time_frame>1 year</time_frame>
      <description>The density, H-score of each marker in paraffin-embedded tissue sections detected by mIHC</description>
    </other_outcome>
    <other_outcome>
      <measure>The expression of PD-1</measure>
      <time_frame>1 year</time_frame>
      <description>The density, H-score of each marker in paraffin-embedded tissue sections detected by mIHC</description>
    </other_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">26</enrollment>
    <condition>Colorectal Neoplasms</condition>
    <arm_group>
      <arm_group_label>Experimental</arm_group_label>
      <description>long course radiotherapy (50 Gy/25f, 2 Gy/f, 5 days/week) for the first 5 weeks and three 21-day cycles capecitabine (1000 mg/m2, bid, po, day1-14) plus three 21-day cycles tislelizumab (200 mg, iv.gtt, day 8) for the first 9 weeks. After that, patients rested for two weeks (week 10-11)。6-8 weeks after the end of radiotherapy, patients underwent TME surgery (12-14 weeks). Thymalfasin was started on the first day of neoadjuvant chemoradiotherapy, 1.6 mg subcutaneously twice a week until the end of the last neoadjuvant treatment.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control</arm_group_label>
      <description>long course radiotherapy (50 Gy/25f, 2 Gy/f, 5 days/week) for the first 5 weeks and three 21-day cycles capecitabine (1000 mg/m2, bid, po, day1-14) plus three 21-day cycles tislelizumab (200 mg, iv.gtt, day 8) for the first 9 weeks. After that, patients rested for two weeks (week 10-11)。6-8 weeks after the end of radiotherapy, patients underwent TME surgery (12-14 weeks).</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Thymalfasin</intervention_name>
      <description>Thymalfasin (thymosin-alpha 1) is an immunomodulating agent able to enhance the Thl immune response. It has been evaluated for its immunomodulatory activities and related therapeutic potential in several diseases.</description>
      <arm_group_label>Experimental</arm_group_label>
    </intervention>
    <biospec_retention>Samples Without DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        Pathology Paraffin Sections （Pre-NCRT and Post-NCRT）&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          locally advanced mid-low rectal cancer&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients with rectal adenocarcinoma must satisfied all the following conditions:&#xD;
  &#xD;
                 1. Stage II/III LARC (cT1-4aN0-2M0);&#xD;
  &#xD;
                 2. Tumor distal location≤10 cm from anal verge (MRI diagnosed);&#xD;
  &#xD;
            -  Patients regardless of gender with aged≥18 years&#xD;
  &#xD;
            -  ECOG score of 0 or 1&#xD;
  &#xD;
            -  Physical and viscera function of patients can withstand major abdominal surgery&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Current or previous active malignancy other than rectal cancer；&#xD;
  &#xD;
            -  Patients underwent major surgery within 4 weeks prior to neoadjuvant therapy；&#xD;
  &#xD;
            -  Patients have any condition affects the absorption of capecitabine through&#xD;
               gastrointestinal tract；&#xD;
  &#xD;
            -  Patients have severe uncontrolled recurrent infections, or other severe uncontrolled&#xD;
               concomitant diseases;&#xD;
  &#xD;
            -  Patients with severe concomitant diseases with estimated survival≤5 years；&#xD;
  &#xD;
            -  Patients with present or previous moderate or severe liver and kidney damage；&#xD;
  &#xD;
            -  Patients preparing for or previously received organ or bone marrow transplant；&#xD;
  &#xD;
            -  Patients who have received immunosuppressive or systemic hormone therapy within 1&#xD;
               month prior to the start of neoadjuvant therapy；&#xD;
  &#xD;
            -  Patients with congenital or acquired immune deficiency (such as HIV infection)；&#xD;
  &#xD;
            -  Pregnant or lactating women.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>Beijing Friendship Hospital, Capital medical University</name>
        <address>
          <city>Beijing</city>
          <state>Xicheng Dis</state>
          <zip>100050</zip>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 8, 2023</study_first_submitted>
    <study_first_submitted_qc>September 5, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 6, 2023</study_first_posted>
    <last_update_submitted>September 5, 2023</last_update_submitted>
    <last_update_submitted_qc>September 5, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 6, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Beijing Friendship Hospital</investigator_affiliation>
      <investigator_full_name>Zhongtao Zhang</investigator_full_name>
      <investigator_title>professor</investigator_title>
    </responsible_party>
    <keyword>Colorectal Neoplasms</keyword>
    <keyword>Programmed Cell Death 1 Receptor</keyword>
    <keyword>Thymalfasin</keyword>
    <keyword>Neoadjuvant Therapy</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Colorectal Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Thymalfasin</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
      <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
      <ipd_info_type>Analytic Code</ipd_info_type>
      <ipd_time_frame>2025.5-</ipd_time_frame>
      <ipd_access_criteria>via reasonable email requests</ipd_access_criteria>
    </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/NCT06024356
  org study id: BFH-TTNCRT
  nct id: NCT06024356
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  It is a single-center, retrospective, controlled study to investigate the efficacy and safety
        of neoadjuvant chemoradiotherapy combined with PD-1 inhibitor and thymalfasin for locally
        advanced mid-low rectal cancer.
  Study Purpose
  
          1. To evaluate the efficacy and safety of neoadjuvant chemoradiotherapy combined with PD-1
             inhibitor and thymalfasin for locally advanced mid-low rectal cancer.
  
          2. To explore the effects of neoadjuvant chemoradiotherapy combined with PD-1 inhibitor and
             thymalfasin on the immune microenvironment of locally advanced mid-low rectal cancer.
  
        Study Design: A single-center, retrospective, controlled study Subjects were divided into two
        groups according to whether or not they received thymalfasin: group 1 was treated with
        neoadjuvant chemoradiotherapy combined with PD-1 inhibitor, and group 2 was treated with
        neoadjuvant chemoradiotherapy combined with PD-1 inhibitor and thymalfasin.
  
        Subjects received long course radiotherapy (50 Gy/25f, 2 Gy/f, 5 days/week) for the first 5
        weeks and three 21-day cycles capecitabine (1000 mg/m2, bid, po, day1-14) plus three 21-day
        cycles tislelizumab (200 mg, iv.gtt, day 8) for the first 9 weeks. After that, patients
        rested for two weeks (week 10-11)。6-8 weeks after the end of radiotherapy, patients underwent
        TME surgery (12-14 weeks). Thymalfasin was started on the first day of neoadjuvant
        chemoradiotherapy, 1.6 mg subcutaneously twice a week until the end of the last neoadjuvant
        treatment.
  
        Enrollment: 26 participants, 13 in each group Study Population: locally advanced mid-low
        rectal cancer Primary Endpoint: pathologic complete response（pCR） Exploratory endpoint:
        Paraffin specimens were collected from biopsies before neoadjuvant therapy and after surgery
        in patients meeting the inclusion criteria. The expression of CD86, CD163, CD4+T，CD8+T，PD-1
        were detected.
  observational model: Case-Control
  time perspective: Retrospective
  measure: pathologic complete response
  time frame: 1 year
  description: All the enrolled patients will receive total mesorectal excision (TME) 7-9 weeks after the end of long course radiotherapy. The rectal specimens will be evaluated by the pathologists who are experienced on the rectal cancer diagnosis according to the 1997 Dworak grading system. The rectal cancer will be classified into 5 grades. Grade 0-3 will be considered as non-pCR while grade 4 represent pCR.
  measure: neoadjuvant rectal (NAR) score
  time frame: 1 year
  description: The neoadjuvant rectal (NAR) score is a promising indicator of survival after preoperative chemoradiotherapy for rectal cancer. The NAR score was calculated according to the following formula: NAR score = [5pN - 3(cT - pT) + 12]2⁄9.61.
  (clinical tumor (cT) stage, pathologic tumor (pT) stage, pathologic nodal (pN) stage)
  measure: tumor regression grade（TRG）
  time frame: 1 year
  description: AJCC 8th TRG classification. TRG 0: No viable cancer cells left in the specimen; complete regression.
  TRG 1: Minimal residual cancer cells present; extensive regression with a minimal number of tumor cells.
  TRG 2: Moderate residual cancer cells present; substantial regression with a significant number of tumor cells.
  TRG 3: Minimal or no regression; no significant tumor cell response to treatment; majority of tumor still present.
  measure: objective response rate (ORR)
  time frame: 1 year
  description: ORR is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The ORR rate is the sum of complete response (CR) and partial response (PR)
  measure: R0 resection rate
  time frame: 1 year
  description: During the surgical process, the surgeon will evaluate the level of cancer resection. It will be classified as R0, R1, R2 resection. Therefore, we can calculate R0 resection rate.
  measure: anal preservation rate
  time frame: 1 year
  description: the surgeon will decide whether the anal can be preserved on the basis of the rectal cancer and intraoperative situation. anal preservation rate is the percentage of patients who achieve anal preservation.
  measure: disease free survival (DFS)
  time frame: 3 year
  description: During the 3-year follow-up, the percentage of the patients who is disease free.
  measure: local recurrence free survival
  time frame: 3 year
  description: During the 3-year follow-up, the percentage of local recurrence.
  measure: overall survival (OS)
  time frame: 3 year
  description: During the 3-year follow-up, the percentage of the patients who is sill survival at the end of follow-up.
  measure: The expression of CD86
  time frame: 1 year
  description: The density, H-score of each marker in paraffin-embedded tissue sections detected by mIHC
  measure: The expression of CD163
  time frame: 1 year
  description: The density, H-score of each marker in paraffin-embedded tissue sections detected by mIHC
  measure: The expression of CD4+
  time frame: 1 year
  description: The density, H-score of each marker in paraffin-embedded tissue sections detected by mIHC
  measure: The expression of CD8+
  time frame: 1 year
  description: The density, H-score of each marker in paraffin-embedded tissue sections detected by mIHC
  measure: The expression of PD-1
  time frame: 1 year
  description: The density, H-score of each marker in paraffin-embedded tissue sections detected by mIHC
  arm group label: Experimental
  description: long course radiotherapy (50 Gy/25f, 2 Gy/f, 5 days/week) for the first 5 weeks and three 21-day cycles capecitabine (1000 mg/m2, bid, po, day1-14) plus three 21-day cycles tislelizumab (200 mg, iv.gtt, day 8) for the first 9 weeks. After that, patients rested for two weeks (week 10-11)。6-8 weeks after the end of radiotherapy, patients underwent TME surgery (12-14 weeks). Thymalfasin was started on the first day of neoadjuvant chemoradiotherapy, 1.6 mg subcutaneously twice a week until the end of the last neoadjuvant treatment.
  arm group label: Control
  description: long course radiotherapy (50 Gy/25f, 2 Gy/f, 5 days/week) for the first 5 weeks and three 21-day cycles capecitabine (1000 mg/m2, bid, po, day1-14) plus three 21-day cycles tislelizumab (200 mg, iv.gtt, day 8) for the first 9 weeks. After that, patients rested for two weeks (week 10-11)。6-8 weeks after the end of radiotherapy, patients underwent TME surgery (12-14 weeks).
  intervention type: Drug
  intervention name: Thymalfasin
  description: Thymalfasin (thymosin-alpha 1) is an immunomodulating agent able to enhance the Thl immune response. It has been evaluated for its immunomodulatory activities and related therapeutic potential in several diseases.
  arm group label: Experimental
  Pathology Paraffin Sections （Pre-NCRT and Post-NCRT）
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  facility: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Beijing Friendship Hospital
  investigator full name: Zhongtao Zhang
  investigator title: professor
  mesh term: Colorectal Neoplasms
  mesh term: Thymalfasin
  sharing ipd: Yes
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd info type: Informed Consent Form (ICF)
  ipd info type: Clinical Study Report (CSR)
  ipd info type: Analytic Code
  ipd time frame: 2025.5-
  ipd access criteria: via reasonable email requests