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/NCT05970302</url>
    </required_header>
    <id_info>
      <org_study_id>NCC-009591</org_study_id>
      <nct_id>NCT05970302</nct_id>
    </id_info>
    <brief_title>XELOX +Bev +Tislelizumab for First-line Treatment of MSS/pMMR RAS-mutated mCRC</brief_title>
    <official_title>XELOX and Bevacizumab in Combination With Tislelizumab for First-Line Treatment of Patients With MSS/pMMR RAS-mutated Metastatic Colorectal Cancer (mCRC): A Single-arm, Phase II Study.</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>
      <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 clinical trial is to compare XELOX +Bev +Tislelizumab with standard&#xD;
        chemotherapy，in MSS/pMMR-type RAS-mutated metastatic colorectal adenocarcinoma. The main&#xD;
        questions it aims to answer are efficacy and safety of the regimen of XELOX +Bev&#xD;
        +Tislelizumab. The investigators want to transform ras-mutated colorectal cancer into a &quot;hot&#xD;
        tumor&quot; through the combination of anti-vascular therapy and chemotherapy, and then achieve&#xD;
        better therapeutic effect through the combination with immunotherapy. Participants will&#xD;
        receive the regimen of XELOX +Bev +Tislelizumab.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 7, 2023</start_date>
    <completion_date type="Anticipated">July 2026</completion_date>
    <primary_completion_date type="Anticipated">July 2025</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>Objective Response Rate (ORR)</measure>
      <time_frame>2 years</time_frame>
      <description>ORR of regimen of XELOX +Bev +Tislelizumab</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Duration of Response (DoR)</measure>
      <time_frame>2 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease Control Rate (DCR);</measure>
      <time_frame>2 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Median Progression-Free Survival (mPFS)</measure>
      <time_frame>2 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>12-month PFS rate</measure>
      <time_frame>12 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Median Overall Survival (mOS)</measure>
      <time_frame>5 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]</measure>
      <time_frame>2 years</time_frame>
      <description>Adverse Events (AEs) Incidence, Serious Adverse Events (SAE) Incidence</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">52</enrollment>
    <condition>Tislelizumab</condition>
    <condition>Bevacizumab</condition>
    <condition>Oxaliplatin</condition>
    <condition>Capecitabine</condition>
    <condition>MSS/pMMR</condition>
    <condition>Metastatic Colorectal Cancer (mCRC)</condition>
    <condition>RAS-mutated</condition>
    <condition>First-Line</condition>
    <arm_group>
      <arm_group_label>XELOX +Bev +Tislelizumab</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Every 3 weeks as a cycle:&#xD;
  Tislelizumab: 200mg, iv, d1;&#xD;
  Bevacizumab: 7.5mg/kg, iv, d1;&#xD;
  Oxaliplatin: 130mg/m2, iv, d1;&#xD;
  Capecitabine: 1000mg/m2, bid, po, d1-d14; Re-evaluate patients every two cycles. If the patient has been treated for more than 8 cycles, they will enter maintenance therapy, and the regimen is capecitabine + BEV combined with tislelizumab.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Tislelizumab+Bevacizumab+Oxaliplatin+Capecitabine</intervention_name>
      <description>Use the above medications on a regular basis.</description>
      <arm_group_label>XELOX +Bev +Tislelizumab</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Histologically confirmed initially unresectable MSS/pMMR-type RAS-mutant metastatic&#xD;
               colorectal adenocarcinoma;&#xD;
  &#xD;
            2. ECOG score of 0 or 1;&#xD;
  &#xD;
            3. Ability to swallow oral medications;&#xD;
  &#xD;
            4. Have at least one measurable lesion (according to RECIST v1.1 standard);&#xD;
  &#xD;
            5. No anti-tumor treatment has been received after recurrence and metastasis;&#xD;
  &#xD;
            6. Neoadjuvant or adjuvant chemotherapy containing fluorouracil drugs is allowed before&#xD;
               or after radical resection of colorectal cancer, but the treatment needs to be&#xD;
               completed for ≥ 6 months; if oxaliplatin is used in neoadjuvant or adjuvant&#xD;
               chemotherapy, it includes The oxaliplatin regimen needs to be completed for ≥12&#xD;
               months;&#xD;
  &#xD;
            7. Adequate organ function: On the premise of no component blood transfusion within 14&#xD;
               days: white blood cells ≥ 3.5*10^9/L and neutrophils ≥ 1.5*10^9/L, hemoglobin ≥ 90g/L,&#xD;
               platelets ≥ 100* 10^9/L; serum bilirubin ≤ 1.5 times the normal value, alanine&#xD;
               aminotransferase (ALT) ≤ 2.5 times the normal value, aspartate aminotransferase (AST)&#xD;
               ≤ 2.5 times the normal value; Urinary protein &lt;2+. Or urine protein 2+ but 24-hour&#xD;
               urine protein quantity ≤ 1 g; serum creatinine ≤ 1.5 times of normal value, creatinine&#xD;
               clearance rate ≥ 60ml/min; Doppler ultrasound evaluation: left ventricular ejection&#xD;
               fraction (LVEF) ≥ lower limit of normal value (50%);&#xD;
  &#xD;
            8. Expected survival period ≥ 3 months;&#xD;
  &#xD;
            9. Patients fully understand this research, voluntarily participate in this clinical&#xD;
               trial and sign an informed consent;&#xD;
  &#xD;
           10. Women with reproductive potential (&lt; 2 years after the last menstrual period) and men&#xD;
               use effective contraceptive methods until half a year after the last treatment.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Previously received bevacizumab or anti-CTLA4, anti-PD-1/PD-L1 therapeutic antibodies&#xD;
               or pathway-targeted drugs;&#xD;
  &#xD;
            2. Received radiotherapy within 4 weeks before the evaluation;&#xD;
  &#xD;
            3. Symptomatic peripheral neuropathy &gt; grade 2 (CTCAE5.0 standard);&#xD;
  &#xD;
            4. Received live vaccine or systemic immune stimulant (including but not limited to&#xD;
               interferon or interleukin 2) within 1 month;&#xD;
  &#xD;
            5. HIV-positive and other immunodeficiency diseases;&#xD;
  &#xD;
            6. Active hepatitis B or hepatitis C (except for those who have been infected or cured&#xD;
               before, that is, HBsAg negative and hepatitis B core antigen anti-HBc antibody&#xD;
               positive; except for hepatitis C patients whose HCV RNA is negative by PCR);&#xD;
  &#xD;
            7. Existing autoimmune diseases or other diseases that require immunosuppressant&#xD;
               treatment, except for type 1 diabetes; except for hypothyroidism that only requires&#xD;
               hormone replacement therapy; skin diseases that do not require systemic treatment&#xD;
               (such as vitiligo, psoriasis, alopecia areata); inhaled or topical steroids or&#xD;
               equivalent steroids in excess of 10 mg prednisone per day, except for inactive&#xD;
               autoimmune disease on adrenal replacement therapy;&#xD;
  &#xD;
            8. Received systemic hormone therapy or treatment with a daily dose of more than 10 mg&#xD;
               prednisone equivalent dose or other forms of immunosuppressive treatment within 7&#xD;
               days, but inhaled or topical steroids or daily application of more than 10 mg&#xD;
               prednisone, etc. Except for inactive autoimmune diseases treated with adrenal&#xD;
               replacement therapy with potent steroids;&#xD;
  &#xD;
            9. Have a history of organ transplantation;&#xD;
  &#xD;
           10. Uncontrolled central nervous system (CNC) metastasis (symptomatic or metastatic sites&#xD;
               are midbrain, pons, medulla or spinal cord) or other central nervous system diseases;&#xD;
  &#xD;
           11. Those who have undergone major surgery, open biopsy or obvious traumatic trauma within&#xD;
               1 month, or who may need major surgery during the study period; those who have&#xD;
               undergone open biopsy or obvious traumatic trauma, or may need major surgery during&#xD;
               the study period;&#xD;
  &#xD;
           12. Combined with other malignant tumors other than intestinal cancer (except cured basal&#xD;
               cell carcinoma or squamous cell carcinoma of the skin and carcinoma in situ of the&#xD;
               cervix; the treatment of other malignant tumors has been completed for more than 1&#xD;
               year, and there is no clinical and imaging evidence of recurrence or progression&#xD;
               except);&#xD;
  &#xD;
           13. Combined active and refractory infection;&#xD;
  &#xD;
           14. Cardiovascular diseases with clinical significance, such as cardiovascular accident&#xD;
               (CVA) (≤ 6 months before treatment), myocardial infarction (≤ 6 months before&#xD;
               treatment), unstable angina, chronic heart failure of NYHA ≥ 2 (CHF), uncontrolled&#xD;
               arrhythmia; uncontrolled hypertension; thromboembolic or bleeding events within 6&#xD;
               months before treatment;&#xD;
  &#xD;
           15. Evidence of causing coagulation disease;&#xD;
  &#xD;
           16. With dysphagia, active peptic ulcer, complete or incomplete intestinal obstruction,&#xD;
               active gastrointestinal bleeding, perforation, malabsorption syndrome or&#xD;
               uncontrollable gastrointestinal inflammatory disease (such as Crohn's disease or&#xD;
               ulcerative colon inflammation);&#xD;
  &#xD;
           17. Severe unhealed wounds/ulcers or severe fractures;&#xD;
  &#xD;
           18. Any serious acute or chronic medical condition that may affect the patient's&#xD;
               participation in the study or interfere with the interpretation of the study results;&#xD;
  &#xD;
           19. There are mental illnesses, serious social and psychological illnesses, or researchers&#xD;
               believe that there are factors that may affect research compliance;&#xD;
  &#xD;
           20. Pregnant or lactating women;&#xD;
  &#xD;
           21. No therapeutic anticoagulant or antiplatelet drugs or NSAIDs (aspirin ≤ 325 mg/day&#xD;
               allowed);&#xD;
  &#xD;
           22. Severe allergic reaction to the test drug;&#xD;
  &#xD;
           23. Reluctance to use alternative therapies such as (but not limited to) bisphosphonates&#xD;
               if receiving RANKL inhibitors (eg, denosumab).&#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>Lin Yang</name>
        <address>
          <city>Beijing</city>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>lin yang</last_name>
        <phone>13611267380</phone>
        <email>linyangcicams@126.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 6, 2023</study_first_submitted>
    <study_first_submitted_qc>July 21, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>July 21, 2023</last_update_submitted>
    <last_update_submitted_qc>July 21, 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>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</investigator_affiliation>
      <investigator_full_name>LIN YANG</investigator_full_name>
      <investigator_title>chief physician</investigator_title>
    </responsible_party>
    <keyword>Single-arm</keyword>
    <keyword>Phase II</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>Bevacizumab</mesh_term>
      <mesh_term>Tislelizumab</mesh_term>
      <mesh_term>Capecitabine</mesh_term>
      <mesh_term>Oxaliplatin</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Undecided</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/NCT05970302
  org study id: NCC-009591
  nct id: NCT05970302
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this clinical trial is to compare XELOX +Bev +Tislelizumab with standard
        chemotherapy，in MSS/pMMR-type RAS-mutated metastatic colorectal adenocarcinoma. The main
        questions it aims to answer are efficacy and safety of the regimen of XELOX +Bev
        +Tislelizumab. The investigators want to transform ras-mutated colorectal cancer into a "hot
        tumor" through the combination of anti-vascular therapy and chemotherapy, and then achieve
        better therapeutic effect through the combination with immunotherapy. Participants will
        receive the regimen of XELOX +Bev +Tislelizumab.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Objective Response Rate (ORR)
  time frame: 2 years
  description: ORR of regimen of XELOX +Bev +Tislelizumab
  measure: Duration of Response (DoR)
  time frame: 2 years
  measure: Disease Control Rate (DCR);
  time frame: 2 years
  measure: Median Progression-Free Survival (mPFS)
  time frame: 2 years
  measure: 12-month PFS rate
  time frame: 12 months
  measure: Median Overall Survival (mOS)
  time frame: 5 years
  measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
  time frame: 2 years
  description: Adverse Events (AEs) Incidence, Serious Adverse Events (SAE) Incidence
  arm group label: XELOX +Bev +Tislelizumab
  arm group type: Experimental
  description: Every 3 weeks as a cycle:
  Tislelizumab: 200mg, iv, d1;
  Bevacizumab: 7.5mg/kg, iv, d1;
  Oxaliplatin: 130mg/m2, iv, d1;
  Capecitabine: 1000mg/m2, bid, po, d1-d14; Re-evaluate patients every two cycles. If the patient has been treated for more than 8 cycles, they will enter maintenance therapy, and the regimen is capecitabine + BEV combined with tislelizumab.
  intervention type: Drug
  intervention name: Tislelizumab+Bevacizumab+Oxaliplatin+Capecitabine
  description: Use the above medications on a regular basis.
  arm group label: XELOX +Bev +Tislelizumab
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
  investigator full name: LIN YANG
  investigator title: chief physician
  mesh term: Colorectal Neoplasms
  mesh term: Bevacizumab
  mesh term: Tislelizumab
  mesh term: Capecitabine
  mesh term: Oxaliplatin
  sharing ipd: Undecided