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/NCT06009848</url>
    </required_header>
    <id_info>
      <org_study_id>AK104-MIBC</org_study_id>
      <nct_id>NCT06009848</nct_id>
    </id_info>
    <brief_title>Cadonilimab Plus Nab-Paclitaxel for Recurrent or Metastatic Muscle Invasive Bladder Cancer</brief_title>
    <official_title>An Open ,Single Arm, Prospective, Phase II Clinical Study on the First-line Treatment of Recurrent or Metastatic Muscle Invasive Bladder Cancer With Cadonilimab(AK104) Plus Nab-Paclitaxel</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Tianjin Medical University Second Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Tianjin Medical University Second 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>
        The goal of this clinical trial is to evaluate the efficacy and safety of Cadonilimab(AK104)&#xD;
        combined with Nab -Paclitaxel as first line therapy for recurrent or metastatic muscle&#xD;
        invasive bladder. Eligible participants will receive AK104 (up to 24 months) plus&#xD;
        Nab-Paclitaxel (for 6 cycles) until radiologic disease progression, unacceptable toxicity, or&#xD;
        withdrawal from the study, whichever occurred first. The primary endpoint is objective&#xD;
        response rate.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Cadonilimab(AK104) is a first-in-class bispecific, humanized IgG1 antibody targeting PD-1 and&#xD;
        CTLA-4, which has the potential to boost immune surveillance in tumors. The goal of this&#xD;
        clinical phase II trial is to evaluate the efficacy and safety of AK104 combined with&#xD;
        Nab-Paclitaxel as first line therapy for recurrent or metastatic muscle invasive bladder.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">October 10, 2022</start_date>
    <completion_date type="Anticipated">October 2025</completion_date>
    <primary_completion_date type="Anticipated">October 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>The last subject completes at least 24 weeks of follow-up (or disease progression)</time_frame>
      <description>The proportion of patients whose tumor volume is reduced to 30% and can be maintained for more than 4 weeks,Based on RECIST v1.1.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall Survival(OS)</measure>
      <time_frame>24 months</time_frame>
      <description>The time from the patient receiving treatment to the death of the patient for any reason,OS evaluated according to RECIST v1.1.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-free Survival(PFS)</measure>
      <time_frame>The last subject completes at least 24 weeks of follow-up (or disease progression)</time_frame>
      <description>The time from the beginning of the patient's treatment to the disease progression or death for any reason.Based on RECIST v1.1.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of Response(DOR)</measure>
      <time_frame>The last subject completes at least 24 weeks of follow-up (or disease progression)</time_frame>
      <description>Duration of response (DOR) as assessed by the investigator according to RECIST v1.1.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adverse events(AEs）</measure>
      <time_frame>24 months</time_frame>
      <description>Include Treatment emerge adverse events, treatment related adverse events and serious adverse events,AEs evaluated according to NCI-CTCAE v5.0 and irAE.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Bladder Cancer</condition>
    <arm_group>
      <arm_group_label>Cadonilimab (AK104) combined with Nab -Paclitaxel</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Cadonilimab (10 mg/kg, administered on the first day of each cycle, Q3W, until there is no clinical benefit)+Nab-Paclitaxel(200 mg/m2, Q3W, 6cycles), every 3 weeks (21 days) is a treatment cycle</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cadonilimab</intervention_name>
      <description>Cadonilimab (10 mg/kg, administered on the first day of each cycle, Q3W, until there is no clinical benefit)+Nab-Paclitaxel(200 mg/m2, Q3W ,6 cycles), every 3 weeks (21 days) is a treatment cycle.</description>
      <arm_group_label>Cadonilimab (AK104) combined with Nab -Paclitaxel</arm_group_label>
      <other_name>AK104</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Sign a written informed consent form before joining the group.&#xD;
  &#xD;
            2. Age&gt;18 years old.&#xD;
  &#xD;
            3. Patients with advanced metastatic bladder cancer confirmed histologically or&#xD;
               pathologically.&#xD;
  &#xD;
            4. Have not received systemic treatment.&#xD;
  &#xD;
            5. Have measurable lesions (according to RECIST 1.1 standard, non lymph node lesions have&#xD;
               a CT scan length of ≥ 10 mm, and lymph node lesions have a CT scan short diameter of ≥&#xD;
               15 mm).&#xD;
  &#xD;
            6. ECOG PS score: 0-1.&#xD;
  &#xD;
            7. The expected survival period is greater than 12 weeks.&#xD;
  &#xD;
            8. The functions of important organs meet the following requirements (excluding the use&#xD;
               of any blood components and cell growth factors within 14 days):&#xD;
  &#xD;
          (1) Blood routine: Neutrophils ≥ 1.5 × 10^9/L;Platelet count ≥ 100 × 10^9/L;Hemoglobin ≥&#xD;
          90g/L.&#xD;
  &#xD;
          (2) Liver and kidney function:Serum creatinine (SCr) ≤ 1.5 times the upper limit of normal&#xD;
          value (ULN) or creatinine clearance rate ≥ 50 ml/min (Cockcroft Fault formula);Liver&#xD;
          function: Aspartate aminotransferase (AST) ≤ 2.5 x ULN, alanine liver aminotransferase&#xD;
          (ALT) ≤ 2.5 x ULN in subjects without liver metastasis; ALT and AST&lt;5 x ULN in liver&#xD;
          metastasis subjects.;Total serum bilirubin (TBIL) ≤ 1.5 x ULN (excluding Gilbert syndrome&#xD;
          where TBIL&lt;3.0 mg/dL);Urinary protein&lt;2+;If the urine protein is ≥ 2+, the 24-hour urine&#xD;
          protein quantitative display must be ≤ 1g.&#xD;
  &#xD;
          9. Normal coagulation function, no active bleeding or thrombosis disease&#xD;
  &#xD;
            1. International standardized ratio INR ≤ 1.5 × ULN;&#xD;
  &#xD;
            2. Partial thromboplastin time APTT ≤ 1.5 × ULN;&#xD;
  &#xD;
            3. Prothrombin time PT ≤ 1.5 × ULN. 10. Non surgical sterilization or reproductive age&#xD;
               female patients are required to use a medically approved contraceptive method (such as&#xD;
               an intrauterine device, contraceptive pill, or condom) during the study treatment&#xD;
               period and within 3 months after the end of the study treatment period. Non surgically&#xD;
               sterilized female patients of childbearing age must have a negative serum or urine HCG&#xD;
               test within 7 days before enrollment in the study. And it must be non lactating.&#xD;
  &#xD;
          11. The subjects voluntarily joined this study with good compliance, safety, and survival&#xD;
          follow-up.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. The subject has previously or simultaneously suffered from other malignant tumors&#xD;
               (excluding cured skin basal cell carcinoma and cervical carcinoma in situ).&#xD;
  &#xD;
            2. The subject is known to have previous allergies to macromolecular protein formulations&#xD;
               or known to be allergic to the drug components used.&#xD;
  &#xD;
            3. The subject has any active autoimmune disease or a history of autoimmune disease (For&#xD;
               example, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis,&#xD;
               enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism,&#xD;
               decreased thyroid function, who have undergone thyroid surgery in the past cannot be&#xD;
               included. subjects with vitiligo or complete remission of childhood asthma, who do not&#xD;
               require any intervention in adulthood, can be included. subjects who require&#xD;
               bronchodilators for medical intervention) Asthma cannot be included).&#xD;
  &#xD;
            4. The subject is currently using immunosuppressive agents or systemic or absorbable&#xD;
               local hormone therapy to achieve immunosuppressive effects (dosage&gt;10mg/day of&#xD;
               prednisone or other therapeutic hormones), and continues to use them within 2 weeks&#xD;
               before enrollment.&#xD;
  &#xD;
            5. Ascites or pleural effusion with clinical symptoms require therapeutic puncture or&#xD;
               drainage.&#xD;
  &#xD;
            6. Patients with clinically uncontrollable cardiac symptoms or diseases, such as: (1)&#xD;
               NYHA grade 2 or above heart failure, (2) unstable angina pectoris, (3) myocardial&#xD;
               infarction within 1 year, (4) clinically significant supraventricular or ventricular&#xD;
               arrhythmias that require treatment or intervention.&#xD;
  &#xD;
            7. The subject has an active infection or an unexplained fever&gt;38.5 degrees Celsius&#xD;
               during the screening period or before the first administration (according to the&#xD;
               researcher's judgment, the subject's fever caused by the tumor can be included in the&#xD;
               group).&#xD;
  &#xD;
            8. Patients with past and current history of pulmonary fibrosis, interstitial pneumonia,&#xD;
               pneumoconiosis, radiation pneumonia, drug-related pneumonia, and severe impairment of&#xD;
               lung function with objective evidence.&#xD;
  &#xD;
            9. Subjects have congenital or acquired immune deficiency, such as HIV infected persons,&#xD;
               or active hepatitis (transaminase does not meet the inclusion criteria, hepatitis B&#xD;
               reference: HBV DNA ≥ 1000 IU/ml. hepatitis C reference: HCV RNA ≥ 1000 IU/ml). Chronic&#xD;
               hepatitis B virus carriers with HBV DNA&lt;2000 IU/ml must receive antiviral treatment&#xD;
               simultaneously during the trial period before they can be enrolled.&#xD;
  &#xD;
           10. Live vaccines may be administered less than 4 weeks before the study medication or&#xD;
               during the study period.&#xD;
  &#xD;
           11. The subject is known to have a history of psychotropic substance abuse, alcoholism, or&#xD;
               drug abuse.&#xD;
  &#xD;
           12. Accepted Chinese herbal medicine or traditional Chinese patent medicines and simple&#xD;
               preparations with anti-tumor indications within 2 weeks before the first&#xD;
               administration.&#xD;
  &#xD;
           13. The researcher believes that it should be excluded from this study. For example, based&#xD;
               on the researcher's judgment, the subject may have other factors that may cause the&#xD;
               study to be terminated midway, such as other serious diseases (including mental&#xD;
               illness) requiring concurrent treatment, serious laboratory test abnormalities,&#xD;
               accompanied by family or social factors, which may affect the safety of the subject,&#xD;
               or the collection of data and samples.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>HaiTao Wang, Ph.D</last_name>
      <phone>+86-022-88326385</phone>
      <email>peterrock2000@126.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Lili Wang, Ph.D</last_name>
      <phone>+86-022-88326610</phone>
      <email>wangliliaigang@163.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Tianjin Medical University Second Hospital</name>
        <address>
          <city>Tianjin</city>
          <state>Tianjin</state>
          <zip>300211</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Haitao Wang, Ph.D</last_name>
        <phone>+86-022-88326385</phone>
        <email>peterrock2000@126.com</email>
      </contact>
      <contact_backup>
        <last_name>Jinhuan Wang, Ph.D</last_name>
        <phone>+86-18202249715</phone>
        <email>wjhhappy2008@163.com</email>
      </contact_backup>
      <investigator>
        <last_name>Haitao Wang</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Jinhuan Wang</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Lili Wang</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Dingkun Hou</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 19, 2023</study_first_submitted>
    <study_first_submitted_qc>August 23, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 24, 2023</study_first_posted>
    <last_update_submitted>August 23, 2023</last_update_submitted>
    <last_update_submitted_qc>August 23, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 24, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Muscle Invasive Bladder Cancer</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Urinary Bladder Neoplasms</mesh_term>
    </condition_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/NCT06009848
  org study id: AK104-MIBC
  nct id: NCT06009848
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this clinical trial is to evaluate the efficacy and safety of Cadonilimab(AK104)
        combined with Nab -Paclitaxel as first line therapy for recurrent or metastatic muscle
        invasive bladder. Eligible participants will receive AK104 (up to 24 months) plus
        Nab-Paclitaxel (for 6 cycles) until radiologic disease progression, unacceptable toxicity, or
        withdrawal from the study, whichever occurred first. The primary endpoint is objective
        response rate.
  Cadonilimab(AK104) is a first-in-class bispecific, humanized IgG1 antibody targeting PD-1 and
        CTLA-4, which has the potential to boost immune surveillance in tumors. The goal of this
        clinical phase II trial is to evaluate the efficacy and safety of AK104 combined with
        Nab-Paclitaxel as first line therapy for recurrent or metastatic muscle invasive bladder.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Objective Response Rate(ORR)
  time frame: The last subject completes at least 24 weeks of follow-up (or disease progression)
  description: The proportion of patients whose tumor volume is reduced to 30% and can be maintained for more than 4 weeks,Based on RECIST v1.1.
  measure: Overall Survival(OS)
  time frame: 24 months
  description: The time from the patient receiving treatment to the death of the patient for any reason,OS evaluated according to RECIST v1.1.
  measure: Progression-free Survival(PFS)
  time frame: The last subject completes at least 24 weeks of follow-up (or disease progression)
  description: The time from the beginning of the patient's treatment to the disease progression or death for any reason.Based on RECIST v1.1.
  measure: Duration of Response(DOR)
  time frame: The last subject completes at least 24 weeks of follow-up (or disease progression)
  description: Duration of response (DOR) as assessed by the investigator according to RECIST v1.1.
  measure: Adverse events(AEs）
  time frame: 24 months
  description: Include Treatment emerge adverse events, treatment related adverse events and serious adverse events,AEs evaluated according to NCI-CTCAE v5.0 and irAE.
  arm group label: Cadonilimab (AK104) combined with Nab -Paclitaxel
  arm group type: Experimental
  description: Cadonilimab (10 mg/kg, administered on the first day of each cycle, Q3W, until there is no clinical benefit)+Nab-Paclitaxel(200 mg/m2, Q3W, 6cycles), every 3 weeks (21 days) is a treatment cycle
  intervention type: Drug
  intervention name: Cadonilimab
  description: Cadonilimab (10 mg/kg, administered on the first day of each cycle, Q3W, until there is no clinical benefit)+Nab-Paclitaxel(200 mg/m2, Q3W ,6 cycles), every 3 weeks (21 days) is a treatment cycle.
  arm group label: Cadonilimab (AK104) combined with Nab -Paclitaxel
  other name: AK104
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: HaiTao Wang, Ph.D
  phone: +86-022-88326385
  email: peterrock2000@126.com
  last name: Lili Wang, Ph.D
  phone: +86-022-88326610
  email: wangliliaigang@163.com
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  country: China
  responsible party type: Sponsor
  mesh term: Urinary Bladder Neoplasms