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/NCT05970900</url>
    </required_header>
    <id_info>
      <org_study_id>2023XHYG0025-01</org_study_id>
      <nct_id>NCT05970900</nct_id>
    </id_info>
    <brief_title>Preoperative Imatinib Mesylate Combined With Rectal-sparing Surgery in Patients With c-KIT Gene-mutant Rectal GIST</brief_title>
    <acronym>PIRKER</acronym>
    <official_title>Preoperative Imatinib Mesylate Combined With Rectal-sparing Surgery in Patients With c-KIT Gene-mutant Rectal GIST: an Open-label, Single-arm, Phase III Trial（PIRKER）</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Fujian Medical University Union Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Fujian Medical University Union Hospital</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>
        Prior to the implementation of preoperative imatinib mesylate therapy, a considerable&#xD;
        percentage (ranging from 34.5% to 67.5%) of individuals diagnosed with rectal&#xD;
        gastrointestinal stromal tumors (GIST) underwent abdominoperineal resection (APR), a surgical&#xD;
        procedure that involved the removal of the anus and necessitated a permanent colostomy.&#xD;
  &#xD;
        This study aims to investigate the safety and viability of an organ-preserving approach&#xD;
        involving preoperative imatinib mesylate treatment in conjunction with local resection for&#xD;
        rectal GIST, specifically targeting patients with c-KIT gene mutations.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Prior to the implementation of preoperative imatinib mesylate therapy, a considerable&#xD;
        percentage (ranging from 34.5% to 67.5%) of individuals diagnosed with rectal&#xD;
        gastrointestinal stromal tumors (GIST) underwent abdominoperineal resection (APR), a surgical&#xD;
        procedure that involved the removal of the anus and necessitated a permanent colostomy.&#xD;
  &#xD;
        Previous studies have established that preoperative administration of imatinib mesylate&#xD;
        effectively diminishes the size of rectal gastrointestinal stromal tumors (GIST) and enhances&#xD;
        the likelihood of sphincter preservation. After initiating preoperative imatinib mesylate&#xD;
        treatment, the sphincter preservation rate has notably escalated from 4.2% to 33.0%-94.9%.&#xD;
  &#xD;
        In theory, lymph node resection is not required for Gastrointestinal Stromal Tumors (GIST);&#xD;
        the local excision of rectal GIST enables sphincter preservation and yields satisfactory anal&#xD;
        function and quality of life (QoL). Various surgical techniques are utilized for local&#xD;
        excision, including traditional transanal (TA) and transanal minimally invasive surgery&#xD;
        (TAMIS) approaches.&#xD;
  &#xD;
        This study aims to explore the safety and feasibility of an organ-preservation strategy of&#xD;
        preoperative imatinib mesylate combined with local resection in rectal gastrointestinal&#xD;
        stromal tumor (GIST), specifically for patients with c-KIT gene mutations.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">October 1, 2029</completion_date>
    <primary_completion_date type="Anticipated">October 1, 2026</primary_completion_date>
    <phase>Phase 3</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>Organ preservation</measure>
      <time_frame>18 months</time_frame>
      <description>Rectum intact, owing to no total mesorectal excision (TME), no locoregional regrowth unless amenable to limited, curative (R0) salvage surgery by local excision (LE) and no permanent stoma (including a never reversed protective stoma, or a stoma owing to toxicities and/or poor functional outcomes)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>3-year disease-free survival</measure>
      <time_frame>36 months</time_frame>
      <description>The proportion of participants who remain disease-free at 3 years after surgery</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Local recurrence rate</measure>
      <time_frame>36 months</time_frame>
      <description>The local recurrence rate is defined as the incidence detection of a tumor involving the bowel wall only that occurs after LE or TME</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival</measure>
      <time_frame>36 months</time_frame>
      <description>The proportion of participants who remain survival at 3 years after surgery</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>R0 resection rate</measure>
      <time_frame>18 months</time_frame>
      <description>The R0 resection rate is defined as the rate of R0 resection</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Quality of life based on EORTC-QLQs-C30 and EORTC-QLQs-CR29</measure>
      <time_frame>Baseline, 3 months, 12 months, 24 months, and 36 months after surgery</time_frame>
      <description>Quality of life accessed by EORTC-QLQs-C30 and EORTC-QLQs-CR29 questionnaire</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Anorectal function</measure>
      <time_frame>Baseline, 3 months, 12 months, 24 months, and 36 months after surgery</time_frame>
      <description>Anorectal function based on LARS score</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">23</enrollment>
    <condition>Gastrointestinal Stromal Tumor of Rectum</condition>
    <arm_group>
      <arm_group_label>Preoperative Imatinib + local excision</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Following the attainment of the maximum treatment response through imatinib mesylate administration, typically occurring within 6-12 months, as evidenced by two consecutive imaging evaluations, the tumor exhibited no further reduction in size, thus necessitating the selection of surgical intervention.&#xD;
  According to the characteristics of the location of the tumor, the surgeon decides the surgical approach based on the existing literature and the availability of surgical equipment, including:&#xD;
  Local transanal resection (TA)&#xD;
  Local resection transsacralapproach&#xD;
  Local resection via perineal approach&#xD;
  Local resection transvaginal approach</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Imatinib Mesylate</intervention_name>
      <description>For patients with c-KIT exon 11 mutation, imatinib mesylate, 400mg, qd.&#xD;
  For patients with c-KIT exon 9 mutation, imatinib mesylate, 600mg or 800mg, qd.</description>
      <arm_group_label>Preoperative Imatinib + local excision</arm_group_label>
      <other_name>Gleevec</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Local resection</intervention_name>
      <description>According to the characteristics of the location of the tumor, the surgeon decides the surgical approach based on the existing literature and the availability of surgical equipment, including:&#xD;
  Local transanal resection (TA)&#xD;
  Local resection transsacralapproach&#xD;
  Local resection via perineal approach&#xD;
  Local resection transvaginal approach</description>
      <arm_group_label>Preoperative Imatinib + local excision</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Over the age of 18.&#xD;
  &#xD;
            2. Newly pathology-diagnosed rectal GIST&#xD;
  &#xD;
            3. Tumor &gt; 2cm; local resection of R0 is not possible in the initial evaluation.&#xD;
  &#xD;
            4. The lower margin of the tumor is ≤ 5cm from the anal verge.&#xD;
  &#xD;
            5. C-KIT gene mutation.&#xD;
  &#xD;
            6. Male or non-pregnant female.&#xD;
  &#xD;
            7. ECOG score 0-2.&#xD;
  &#xD;
            8. Did not receive targeted therapy before the start of the clinical trial.&#xD;
  &#xD;
            9. Sufficient organ functions are defined as follows:&#xD;
  &#xD;
               Total bilirubin &lt; 1.5×ULN (upper limit of normal, ULN), serum AST (SGOT) and ALT&#xD;
               (SGPT) &lt; 2. 5 × ULN, creatinine &lt; 1.5×ULN, neutrophil count &gt; 1. 5 ×109 / L, platelet&#xD;
               &gt; 100 × 109 / L.&#xD;
  &#xD;
           10. The patient's informed consent has been obtained.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Pathology is non-rectal GIST.&#xD;
  &#xD;
            2. Under the age of 18.&#xD;
  &#xD;
            3. Patients with distant metastasis.&#xD;
  &#xD;
            4. The patient is not permitted to have additional primary malignant tumors within five&#xD;
               years unless those tumors are currently deemed clinically insignificant and do not&#xD;
               necessitate active intervention, such as basal cell skin cancer or cervical cancer in&#xD;
               situ. The presence of any other malignant diseases is strictly prohibited.&#xD;
  &#xD;
            5. Individuals diagnosed with stage III or IV cardiac conditions, specifically congestive&#xD;
               heart failure and myocardial infarction occurring within six months prior to the&#xD;
               commencement of the study.&#xD;
  &#xD;
            6. The patient presents with severe and/or uncontrolled medical ailments, such as&#xD;
               unmanaged diabetes, advanced chronic kidney disease, or active uncontrolled infection.&#xD;
  &#xD;
            7. Co-administration of imatinib with warfarin or acetaminophen is contraindicated,&#xD;
               necessitating the substitution of alternative medications (e.g., low molecular weight&#xD;
               heparin in place of warfarin).&#xD;
  &#xD;
            8. Subjects undergoing radiotherapy, chemotherapy, and/or targeted therapy.&#xD;
  &#xD;
            9. Pregnant or lactating female patients.&#xD;
  &#xD;
           10. Cognitive or psychiatric disorders.&#xD;
  &#xD;
           11. Profound cardiac, hepatic, and renal dysfunction.&#xD;
  &#xD;
           12. Non-adherence by the patient or the researchers' assessment of the patient's inability&#xD;
               to complete the entire trial.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>80 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Weizhong Jiang, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Fujian Medical University Union Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Weizhong Jiang, MD</last_name>
      <phone>+8613763828825</phone>
      <email>Jiangwz362100@163.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Jiabin Zheng</last_name>
      <phone>+8613365910080</phone>
      <email>xhyykjk@163.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Weizhong Jiang</name>
        <address>
          <city>Fuzhou</city>
          <state>Fujian</state>
          <zip>350001</zip>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 23, 2023</study_first_submitted>
    <study_first_submitted_qc>July 23, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>July 23, 2023</last_update_submitted>
    <last_update_submitted_qc>July 23, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Fujian Medical University Union Hospital</investigator_affiliation>
      <investigator_full_name>蒋伟忠</investigator_full_name>
      <investigator_title>Associate professor</investigator_title>
    </responsible_party>
    <keyword>Gastrointestinal Stromal Tumor</keyword>
    <keyword>Rectum</keyword>
    <keyword>Imatinib mesylate</keyword>
    <keyword>c-KIT gene</keyword>
    <keyword>Local resection</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Gastrointestinal Stromal Tumors</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Imatinib Mesylate</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/NCT05970900
  org study id: 2023XHYG0025-01
  nct id: NCT05970900
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Prior to the implementation of preoperative imatinib mesylate therapy, a considerable
        percentage (ranging from 34.5% to 67.5%) of individuals diagnosed with rectal
        gastrointestinal stromal tumors (GIST) underwent abdominoperineal resection (APR), a surgical
        procedure that involved the removal of the anus and necessitated a permanent colostomy.
  
        This study aims to investigate the safety and viability of an organ-preserving approach
        involving preoperative imatinib mesylate treatment in conjunction with local resection for
        rectal GIST, specifically targeting patients with c-KIT gene mutations.
  Prior to the implementation of preoperative imatinib mesylate therapy, a considerable
        percentage (ranging from 34.5% to 67.5%) of individuals diagnosed with rectal
        gastrointestinal stromal tumors (GIST) underwent abdominoperineal resection (APR), a surgical
        procedure that involved the removal of the anus and necessitated a permanent colostomy.
  
        Previous studies have established that preoperative administration of imatinib mesylate
        effectively diminishes the size of rectal gastrointestinal stromal tumors (GIST) and enhances
        the likelihood of sphincter preservation. After initiating preoperative imatinib mesylate
        treatment, the sphincter preservation rate has notably escalated from 4.2% to 33.0%-94.9%.
  
        In theory, lymph node resection is not required for Gastrointestinal Stromal Tumors (GIST);
        the local excision of rectal GIST enables sphincter preservation and yields satisfactory anal
        function and quality of life (QoL). Various surgical techniques are utilized for local
        excision, including traditional transanal (TA) and transanal minimally invasive surgery
        (TAMIS) approaches.
  
        This study aims to explore the safety and feasibility of an organ-preservation strategy of
        preoperative imatinib mesylate combined with local resection in rectal gastrointestinal
        stromal tumor (GIST), specifically for patients with c-KIT gene mutations.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Organ preservation
  time frame: 18 months
  description: Rectum intact, owing to no total mesorectal excision (TME), no locoregional regrowth unless amenable to limited, curative (R0) salvage surgery by local excision (LE) and no permanent stoma (including a never reversed protective stoma, or a stoma owing to toxicities and/or poor functional outcomes)
  measure: 3-year disease-free survival
  time frame: 36 months
  description: The proportion of participants who remain disease-free at 3 years after surgery
  measure: Local recurrence rate
  time frame: 36 months
  description: The local recurrence rate is defined as the incidence detection of a tumor involving the bowel wall only that occurs after LE or TME
  measure: Overall survival
  time frame: 36 months
  description: The proportion of participants who remain survival at 3 years after surgery
  measure: R0 resection rate
  time frame: 18 months
  description: The R0 resection rate is defined as the rate of R0 resection
  measure: Quality of life based on EORTC-QLQs-C30 and EORTC-QLQs-CR29
  time frame: Baseline, 3 months, 12 months, 24 months, and 36 months after surgery
  description: Quality of life accessed by EORTC-QLQs-C30 and EORTC-QLQs-CR29 questionnaire
  measure: Anorectal function
  time frame: Baseline, 3 months, 12 months, 24 months, and 36 months after surgery
  description: Anorectal function based on LARS score
  arm group label: Preoperative Imatinib + local excision
  arm group type: Experimental
  description: Following the attainment of the maximum treatment response through imatinib mesylate administration, typically occurring within 6-12 months, as evidenced by two consecutive imaging evaluations, the tumor exhibited no further reduction in size, thus necessitating the selection of surgical intervention.
  According to the characteristics of the location of the tumor, the surgeon decides the surgical approach based on the existing literature and the availability of surgical equipment, including:
  Local transanal resection (TA)
  Local resection transsacralapproach
  Local resection via perineal approach
  Local resection transvaginal approach
  intervention type: Drug
  intervention name: Imatinib Mesylate
  description: For patients with c-KIT exon 11 mutation, imatinib mesylate, 400mg, qd.
  For patients with c-KIT exon 9 mutation, imatinib mesylate, 600mg or 800mg, qd.
  arm group label: Preoperative Imatinib + local excision
  other name: Gleevec
  intervention type: Procedure
  intervention name: Local resection
  description: According to the characteristics of the location of the tumor, the surgeon decides the surgical approach based on the existing literature and the availability of surgical equipment, including:
  Local transanal resection (TA)
  Local resection transsacralapproach
  Local resection via perineal approach
  Local resection transvaginal approach
  arm group label: Preoperative Imatinib + local excision
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 80 Years
  healthy volunteers: No
  last name: Weizhong Jiang, MD
  role: Principal Investigator
  affiliation: Fujian Medical University Union Hospital
  last name: Weizhong Jiang, MD
  phone: +8613763828825
  email: Jiangwz362100@163.com
  last name: Jiabin Zheng
  phone: +8613365910080
  email: xhyykjk@163.com
  facility: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Fujian Medical University Union Hospital
  investigator full name: 蒋伟忠
  investigator title: Associate professor
  mesh term: Gastrointestinal Stromal Tumors
  mesh term: Imatinib Mesylate
  sharing ipd: No