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/NCT06039891</url>
    </required_header>
    <id_info>
      <org_study_id>K4391</org_study_id>
      <nct_id>NCT06039891</nct_id>
    </id_info>
    <brief_title>Nimotuzumab Plus Tislelizumab for Recurrent and Metastatic Cervical Cancer</brief_title>
    <official_title>A Single-arm, Single-center, Prospective, Phase II Study of Nimotuzumab, Tislelizumab Plus Radiotherapy for Recurrent and Metastatic Cervical Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Peking Union Medical College Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Peking Union Medical College 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>
        Patients with recurrent or metastatic cervical cancer have very poor prognosis. For eligible&#xD;
        patients, radiotherapy remains the choice, which has the most effective impact on the&#xD;
        survival periods. Epidermal growth factor receptor (EGFR) is overexpressed in cervical cancer&#xD;
        cells, anti-EGFR therapy maybe an ideal target for the treatment of cervical cancer. This&#xD;
        study aims to discover the progression-free survival of combination therapy with nimotuzumab&#xD;
        (an anti-epidermal growth factor receptor [EGFR] IgG1 humanized monoclonal antibody)&#xD;
        、Tislelizumab and radiotherapy in recurrent or metastatic uterine cervical squamous carcinoma&#xD;
        in a single-arm, open, phase 2 clinical trial.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Nimotuzumab, is a humanized antibody recognizing with high affinity the epidermal&#xD;
        growthfactor (EGF-R)，has shown promising efficacy and tolerable toxicity in the cervical&#xD;
        cancer. In this study, patients with recurrent or metastatic cervical cancer, will be&#xD;
        included in this study according to the prescribed criteria in the protocal. Nimotuzumab 400&#xD;
        mg/time, intravenous injection, qw; Tislelizumab 200 mg/time, q3w until disease progression,&#xD;
        intolerable toxicity, or 24 months of medication. Assess objective response rate;&#xD;
        progression-free survival; median overall survival and safety ( adverse event).&#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, 2027</completion_date>
    <primary_completion_date type="Anticipated">October 1, 2024</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>Single Group Assignment</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Progression-free survival (PFS)</measure>
      <time_frame>one year</time_frame>
      <description>Progression-free survival is defined as the time from the start of treatment with caldonirimab and nimotuzumab until the first documentation of disease progression or death due to any cause, whichever occurs first</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Objective response rate (ORR)</measure>
      <time_frame>one year</time_frame>
      <description>ORR is defined as the proportion of subjects with confirmed CR or PR, based on RECIST v1.1</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Median Overall survival（mOS）</measure>
      <time_frame>three years</time_frame>
      <description>Overall survival from the start of study to the disease progression</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adverse events (AEs)</measure>
      <time_frame>three years</time_frame>
      <description>An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">55</enrollment>
    <condition>Cervical Cancer</condition>
    <arm_group>
      <arm_group_label>Nimotuzumab, Tislelizumab group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Subjects will receive Nimotuzumab 400 mg/time, intravenous injection, qw; Tislelizumab 200 mg/time, q3w until disease progression, intolerable toxicity, or 24 months of medication</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Nimotuzumab、Tislelizumab</intervention_name>
      <description>Subjects will receive Nimotuzumab 400 mg/time, intravenous injection, qw; Tislelizumab 200 mg/time, q3w until disease progression, intolerable toxicity, or 24 months of medication</description>
      <arm_group_label>Nimotuzumab, Tislelizumab group</arm_group_label>
      <other_name>Nimotuzumab, Tislelizumab plus radiotherapy</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age≥18；&#xD;
  &#xD;
            2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 2；&#xD;
  &#xD;
            3. Have recurrent, or metastatic squamous cell carcinoma, adenosquamous carcinoma, or&#xD;
               adenocarcinoma of the cervix；&#xD;
  &#xD;
            4. Oligometastases and Oligo-recurrence( number of metastatic organs ≤3, and the total&#xD;
               number of metastases ≤5), with indications for radiotherapy, and which has not been&#xD;
               treated with systemic chemotherapy；&#xD;
  &#xD;
            5. At least one measurable lesion defined by Response Evaluation Criteria in Solid Tumors&#xD;
               (RECIST) guideline 1.1；&#xD;
  &#xD;
            6. Anticipative survival period of 3 months or more；&#xD;
  &#xD;
            7. Have adequate organ function as indicated by the following laboratory values： (1)&#xD;
               Hematological：Absolute neutrophil count&#xD;
               (ANC)≥1.5×109/L；Platelets(PLT)≥90×109/L；Hemoglobin(Hb)≥90 g/L； (2) Hepatic：Serum total&#xD;
               bilirubin (TBIL)≤2.5×ULN；ALT 和 AST≤2×ULN； (3) Renal:BUN 和 Cr ≤ 1.5×ULN；&#xD;
  &#xD;
            8. Cardiac ultrasound：LVEF≥50%；&#xD;
  &#xD;
            9. A WOCBP who has a positive blood pregnancy test within 72 hours prior to&#xD;
               randomization（Postmenopausal women who have had amenorrhea for at least 12 months are&#xD;
               considered infertile, and women who are known to have received Tubal ligation do not&#xD;
               require a pregnancy test）；&#xD;
  &#xD;
           10. For subjects who were not menopausal or had not undergone surgical sterilization,&#xD;
               consent to abstinence or use of an effective contraceptive method was given during&#xD;
               treatment and at least 5 months after the last administration of the drug during study&#xD;
               treatment;&#xD;
  &#xD;
           11. Volunteer to join the study, sign informed consent, have good compliance and willing&#xD;
               to cooperate with the follow-up.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Patients who have received prior therapy with an anti-EGFR an anti-PD-1, anti-PD-L1&#xD;
               agent; Has a contraindication or hypersensitivity to Macromolecular protein&#xD;
               preparationsany and component of Nimotuzumab and Tislelizumab&#xD;
  &#xD;
            2. Other malignancies diagnosed within 5 years before the first dose, excluding basal&#xD;
               cell carcinoma of the skin, squamous cell carcinoma of the skin and papillary thyroid&#xD;
               carcinoma;&#xD;
  &#xD;
            3. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy，&#xD;
               prior therapy with other targeted therapy and any anti-vascular endothelial growth&#xD;
               factor (VEGF) drug. Other anti-tumor treatments not included in this trial protocol；&#xD;
  &#xD;
            4. Patients who are pregnant or nursing. Patients of childbearing potential must agree to&#xD;
               use contraceptive measures during study therapy and for at least five months after&#xD;
               completion of this study.&#xD;
  &#xD;
            5. Patients with recto-vaginal fistula,vesicovaginal fistula, uncontrolled vaginal&#xD;
               bleeding and no underlying process leading to fistula；&#xD;
  &#xD;
            6. Major surgical procedure unrelated to cervical cancer,and has not recovered adequately&#xD;
               from toxicity and/or complications from surgery within 4 weeks before enrollment；&#xD;
  &#xD;
            7. Has a known history of human immunodeficiency virus (HIV) infection,or has other&#xD;
               acquired, congenital immunodeficiency disease, or has a history of organ&#xD;
               transplantation；&#xD;
  &#xD;
            8. Uncontrolled hypertension , cardiac arrhythmia and pulmonary disease.Has a known&#xD;
               history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]reactive) or&#xD;
               known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected)&#xD;
               infection.&#xD;
  &#xD;
            9. Has known active Central Nervous System (CNS)metastases and/or carcinomatous&#xD;
               meningitis. Participants with known brain metastases may participate provided that the&#xD;
               brain metastases have been previously treated (except with chemotherapy) and are&#xD;
               radiographically stable more than 2 weeks. Known brain metastases are considered&#xD;
               active, if any of the following criteria are: There were measurable lesions outside&#xD;
               the central nervous system, no metastases to meninges, midbrain, pons, cerebellum,&#xD;
               medulla oblongata or spinal cord, no previous history of intracranial hemorrhage, and&#xD;
               steroid therapy was discontinued 14 days before the first dose of study drug.&#xD;
  &#xD;
           10. Patients with clinical signs or fluids of pleural effusion, ascites, or pericardial&#xD;
               effusion requiring drainage (required or not significantly increased within 3 days of&#xD;
               discontinuation of drainage) may be eligible;&#xD;
  &#xD;
           11. Any previous arterial thrombosis, thrombosis, or ischaemia, such as myocardial&#xD;
               infarction, unstable angina, cerebrovascular accident, etc., occurred in the previous&#xD;
               6 months.A history of deep venous thrombosis or any other serious thromboembolism&#xD;
               (implanted venous port or catheter-derived thrombosis, superficial venous thrombosis,&#xD;
               or thromboembolic stability after conventional therapy were not considered as serious&quot;&#xD;
               thromboembolism&quot; during the first 3 months of enrollment&quot;;&#xD;
  &#xD;
           12. Cancer thrombus in the portal vein involves both the main and right branches of the&#xD;
               portal vein, or both the main and the superior mesenteric and inferior vena cava&#xD;
               thrombus; the superior vena cava thrombus and the superior vena cava syndrome;&#xD;
  &#xD;
           13. Tumour involvement of vital peripheral organs or vessels (such as the great vessels of&#xD;
               the mediastinum, superior vena cava, inferior vena cava, abdominal aorta, iliac&#xD;
               vessels, trachea, esophagus, etc.) or risk of esophageal-tracheal or esophageal&#xD;
               pleural fistula;&#xD;
  &#xD;
           14. History of interstitial pneumonia, pharmacologic pneumonia, radiation pneumonia,&#xD;
               idiopathic pneumonia, or active pneumonia;&#xD;
  &#xD;
           15. Severe infection in active state or under clinical control.Severe infections occurred&#xD;
               within 4 weeks before the first dose, including but not limited to hospitalization for&#xD;
               infection, bacteremia, or complications of severe pneumonia.&#xD;
  &#xD;
           16. Inability to perform internal exposure therapy by the Investigator's assessment；&#xD;
  &#xD;
           17. Patients who do not understand the requirements of the trial or may not comply with&#xD;
               them.&#xD;
  &#xD;
           18. Participants were identified as having any medical, psychiatric, or other condition or&#xD;
               condition that may adversely affect their safety or the reliability of study data.&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>90 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 9, 2023</study_first_submitted>
    <study_first_submitted_qc>September 9, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 15, 2023</study_first_posted>
    <last_update_submitted>September 9, 2023</last_update_submitted>
    <last_update_submitted_qc>September 9, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Peking Union Medical College Hospital</investigator_affiliation>
      <investigator_full_name>Lei Li</investigator_full_name>
      <investigator_title>chief physician, professor</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Uterine Cervical Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Tislelizumab</mesh_term>
      <mesh_term>Nimotuzumab</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/NCT06039891
  org study id: K4391
  nct id: NCT06039891
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Patients with recurrent or metastatic cervical cancer have very poor prognosis. For eligible
        patients, radiotherapy remains the choice, which has the most effective impact on the
        survival periods. Epidermal growth factor receptor (EGFR) is overexpressed in cervical cancer
        cells, anti-EGFR therapy maybe an ideal target for the treatment of cervical cancer. This
        study aims to discover the progression-free survival of combination therapy with nimotuzumab
        (an anti-epidermal growth factor receptor [EGFR] IgG1 humanized monoclonal antibody)
        、Tislelizumab and radiotherapy in recurrent or metastatic uterine cervical squamous carcinoma
        in a single-arm, open, phase 2 clinical trial.
  Nimotuzumab, is a humanized antibody recognizing with high affinity the epidermal
        growthfactor (EGF-R)，has shown promising efficacy and tolerable toxicity in the cervical
        cancer. In this study, patients with recurrent or metastatic cervical cancer, will be
        included in this study according to the prescribed criteria in the protocal. Nimotuzumab 400
        mg/time, intravenous injection, qw; Tislelizumab 200 mg/time, q3w until disease progression,
        intolerable toxicity, or 24 months of medication. Assess objective response rate;
        progression-free survival; median overall survival and safety ( adverse event).
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Progression-free survival (PFS)
  time frame: one year
  description: Progression-free survival is defined as the time from the start of treatment with caldonirimab and nimotuzumab until the first documentation of disease progression or death due to any cause, whichever occurs first
  measure: Objective response rate (ORR)
  time frame: one year
  description: ORR is defined as the proportion of subjects with confirmed CR or PR, based on RECIST v1.1
  measure: Median Overall survival（mOS）
  time frame: three years
  description: Overall survival from the start of study to the disease progression
  measure: Adverse events (AEs)
  time frame: three years
  description: An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment
  arm group label: Nimotuzumab, Tislelizumab group
  arm group type: Experimental
  description: Subjects will receive Nimotuzumab 400 mg/time, intravenous injection, qw; Tislelizumab 200 mg/time, q3w until disease progression, intolerable toxicity, or 24 months of medication
  intervention type: Drug
  intervention name: Nimotuzumab、Tislelizumab
  description: Subjects will receive Nimotuzumab 400 mg/time, intravenous injection, qw; Tislelizumab 200 mg/time, q3w until disease progression, intolerable toxicity, or 24 months of medication
  arm group label: Nimotuzumab, Tislelizumab group
  other name: Nimotuzumab, Tislelizumab plus radiotherapy
  criteria: 
  gender: Female
  minimum age: 18 Years
  maximum age: 90 Years
  healthy volunteers: No
  responsible party type: Principal Investigator
  investigator affiliation: Peking Union Medical College Hospital
  investigator full name: Lei Li
  investigator title: chief physician, professor
  mesh term: Uterine Cervical Neoplasms
  mesh term: Tislelizumab
  mesh term: Nimotuzumab