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/NCT06032845</url>
    </required_header>
    <id_info>
      <org_study_id>2306276-5</org_study_id>
      <nct_id>NCT06032845</nct_id>
    </id_info>
    <brief_title>Cryoablation Combined With Tislelizumab Plus Lenvatinib In Previously Treated Solid Tumors (CASTLE-11)</brief_title>
    <acronym>CASTLE-11</acronym>
    <official_title>A Phase II Study to Evaluate the Efficacy and Safety of Cryoablation Combined With Tislelizumab Plus Lenvatinib in Previously Treated Solid Tumors</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Fudan University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Fudan University</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 objective of this study is to evaluate the efficacy and safety of cryoablation combined&#xD;
        with Tislelizumab plus Lenvatinib for patients with previously treated solid tumors.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Recent studies have suggested that local destruction of tumor tissue by cryoablation induced&#xD;
        activation and maturation of dendritic cells and tumor-specific T cells by cross-presentation&#xD;
        of tumor antigens. While pd-1 blocking antibody interferes with PD-1 mediated T-cell&#xD;
        regulatory signaling. And combination of pd-1 blocking antibody plus lenvatinib showed&#xD;
        increased ORR in many types of human cancers. Therefore, the objective of this study is to&#xD;
        evaluate the efficacy and safety of cryoablation combined with Tislelizumab plus Lenvatinib&#xD;
        in previously treated solid tumors.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">September 13, 2023</start_date>
    <completion_date type="Anticipated">December 30, 2025</completion_date>
    <primary_completion_date type="Anticipated">December 30, 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>
      <intervention_model_description>cryoablation, Tislelizumab, Lenvatinib</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Objective Response Rate (ORR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1</measure>
      <time_frame>max 24 months</time_frame>
      <description>ORR is defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by investigator.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Duration of Response (DOR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1</measure>
      <time_frame>max 24 months</time_frame>
      <description>DOR is defined as the time from first documented complete or partial response until disease progression, death from any cause, or censoring at date of last tumor assessment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression Free Survival (PFS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1</measure>
      <time_frame>max 24 months</time_frame>
      <description>PFS is defined as the time from study treatment to disease progression or all-cause death as assessed by the investigator (whichever occurs first)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1</measure>
      <time_frame>max 24 months</time_frame>
      <description>OS is defined as the time from study treatment to the date of death of the subject, regardless of the cause of death.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease control rate (DCR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1</measure>
      <time_frame>max 24 months</time_frame>
      <description>DCR is defined as the proportion of patients with complete response (CR), partial response (PR) and stable disease (SD)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v5.0</measure>
      <time_frame>max 42 months</time_frame>
      <description>An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience at least one AE will be reported.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">25</enrollment>
    <condition>Solid Tumor, Adult</condition>
    <arm_group>
      <arm_group_label>Cryoablation combined with Tislelizumab and lenvatinib</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Cryoablation treatment starts at day 0. Tislelizumab and Lenvatinib will be initiated on day 1 after cryoablation. Tislelizumab will be administered at 200 mg i.v. every 3 weeks until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent. Lenvatinib will be administered (bodyweight ≥ 60 kg, 12 mg; &lt; 60 kg, 8 mg) orally daily every 3 weeks until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Tislelizumab</intervention_name>
      <description>a PD-1 immune check inhibitor</description>
      <arm_group_label>Cryoablation combined with Tislelizumab and lenvatinib</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Lenvatinib</intervention_name>
      <description>Lenvatinib capsules</description>
      <arm_group_label>Cryoablation combined with Tislelizumab and lenvatinib</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Cryoablation</intervention_name>
      <description>Cryoablation is performed under US or CT guidance per Investigator decision.</description>
      <arm_group_label>Cryoablation combined with Tislelizumab and lenvatinib</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Written informed consent obtained.&#xD;
  &#xD;
            -  Age ≥ 18 years at time of study entry.&#xD;
  &#xD;
            -  Participants must have solid tumors.&#xD;
  &#xD;
            -  Participants must have failed from chemotherapy or other anti-cancer therapy or&#xD;
               standard therapy was no longer feasible.&#xD;
  &#xD;
            -  Participants who had received previous anti-angiogenesis or anti-PD1/PDL1 therapy were&#xD;
               eligible.&#xD;
  &#xD;
            -  At least one measurable site of disease as defined by RECIST v1.1 with spiral CT scan&#xD;
               or MRI.&#xD;
  &#xD;
            -  Performance status (PS) ≤ 2 (ECOG scale).&#xD;
  &#xD;
            -  Life expectancy of at least 12 weeks.&#xD;
  &#xD;
            -  Adequate blood count, liver-enzymes, and renal function: absolute neutrophil count ≥&#xD;
               1,500/L, platelets ≥75 x103/L; Total bilirubin ≤ 3x upper normal limit; Aspartate&#xD;
               Aminotransferase (SGOT), Alanine aminotransferase (SGPT) ≤ 5 x upper normal limit&#xD;
               (ULN); International normalized ratio (INR) ≤1.25; Albumin ≥ 31 g/dL; Serum Creatinine&#xD;
               ≤ 1.5 x institutional ULN or creatinine clearance (CrCl) ≥ 30 mL/min (if using the&#xD;
               Cockcroft-Gault formula )&#xD;
  &#xD;
            -  Female patients with reproductive potential must have a negative urine or serum&#xD;
               pregnancy test within 7 days prior to start of trial.&#xD;
  &#xD;
            -  Subject is willing and able to comply with the protocol for the duration of the study&#xD;
               including undergoing treatment, adherence to contraceptive measures, scheduled visits&#xD;
               and examinations including follow up.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Uncontrolled pericardial effusion, pleural effusion, or clinically significant&#xD;
               moderate or severe ascites that is symptomatic or requires thoracentesis or&#xD;
               paracentesis during the screening phase for control of symptoms.&#xD;
  &#xD;
            -  History of cardiac disease, including clinically significant gastrointestinal bleeding&#xD;
               within 4 weeks prior to start of study treatment.&#xD;
  &#xD;
            -  Thrombotic or embolic events such as cerebrovascular accident (including transient&#xD;
               ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months&#xD;
               Prior to the first dose of study drug with the exception of thrombosis of a segmental&#xD;
               portal vein.&#xD;
  &#xD;
            -  Prior treatment with cryoablation.&#xD;
  &#xD;
            -  Major surgery within 4 weeks of starting the study treatment OR subjects who have not&#xD;
               recovered from effects of major surgery.&#xD;
  &#xD;
            -  Patients with second primary cancer, except adequately treated basal skin cancer or&#xD;
               carcinoma in-situ of the cervix.&#xD;
  &#xD;
            -  Immunocompromised patients, e.g. patients who are known to be serologically positive&#xD;
               for human immunodeficiency virus (HIV).&#xD;
  &#xD;
            -  Any condition or comorbidity that, in the opinion of the investigator, would interfere&#xD;
               with evaluation of study Treatment or interpretation of patient safety or study&#xD;
               results, including but not limited to:&#xD;
  &#xD;
                 1. history of interstitial lung disease&#xD;
  &#xD;
                 2. Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) coinfection (i.e double&#xD;
                    infection)&#xD;
  &#xD;
                 3. known acute or chronic pancreatitis&#xD;
  &#xD;
                 4. active tuberculosis&#xD;
  &#xD;
                 5. any other active infection (viral, fungal or bacterial) requiring systemic&#xD;
                    therapy&#xD;
  &#xD;
                 6. history of allogeneic tissue/solid organ transplant&#xD;
  &#xD;
                 7. diagnosis of immunodeficiency or patient is receiving chronic systemic steroid&#xD;
                    therapy or any other form of immunosuppressive therapy within 7 days prior to the&#xD;
                    first dose of Tislelizumab treatment.&#xD;
  &#xD;
                 8. Has an active autoimmune disease requiring systemic treatment within the past 3&#xD;
                    months or a documented history of clinically severe autoimmune disease, or a&#xD;
                    syndrome that requires systemic steroids or immunosuppressive agents. Exceptions:&#xD;
                    Subjects with vitiligo, hypothyroidism, diabetes mellitus type I or resolved&#xD;
                    childhood asthma/atopy are an exception to this rule. Subjects that require&#xD;
                    intermittent use of bronchodilators or local steroid injections would not be&#xD;
                    excluded from the study. Subjects with Hashimoto thyroiditis, hypothyroidism&#xD;
                    stable on hormone replacement or psoriasis not requiring treatment are not&#xD;
                    excluded from the study.&#xD;
  &#xD;
                 9. Live vaccine within 30 days prior to the first dose of Tislelizumab treatment or&#xD;
                    during study treatment.&#xD;
  &#xD;
                10. History or clinical evidence of Central Nervous System (CNS) metastases&#xD;
                    Exceptions are: Subjects who have completed local therapy and who meet both of&#xD;
                    the following criteria: I. are asymptomatic and II. have no requirement for&#xD;
                    steroids 6 weeks prior to start of Tislelizumab treatment. Screening with CNS&#xD;
                    imaging (CT or MRI) is required only if clinically indicated or if the subject&#xD;
                    has a history of CNS&#xD;
  &#xD;
            -  Medication that is known to interfere with any of the agents applied in the trial.&#xD;
  &#xD;
            -  Any other efficacious cancer treatment except protocol specified treatment at study&#xD;
               start.&#xD;
  &#xD;
            -  Female subjects who are pregnant, breast-feeding or male/female patients of&#xD;
               reproductive potential who are not employing an effective method of birth control&#xD;
               (failure rate of less than 1% per year). [Acceptable methods of contraception are:&#xD;
               implants, injectable contraceptives, combined oral contraceptives, intrauterine&#xD;
               pessars (only hormonal devices), sexual abstinence or vasectomy of the partner]. Women&#xD;
               of childbearing potential must have a negative pregnancy test (serum β-HCG) at&#xD;
               screening.&#xD;
  &#xD;
            -  Patient with any significant history of non-compliance to medical regimens or with&#xD;
               inability to grant reliable informed consent.&#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>Peng Wang, MD</last_name>
      <phone>86-21-64175590</phone>
      <email>wangp413@163.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Peng Wang, MD</last_name>
      <phone>86-21-64175590</phone>
      <email>peng_wang@fudan.edu.cn</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Fudan University Shanghai Cancer Center</name>
        <address>
          <city>Shanghai</city>
          <state>Shanghai</state>
          <zip>200032</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Peng Wang, M.D.</last_name>
        <phone>862164175590</phone>
        <phone_ext>83630</phone_ext>
        <email>peng_wang@fudan.edu.cn</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 5, 2023</study_first_submitted>
    <study_first_submitted_qc>September 5, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 13, 2023</study_first_posted>
    <last_update_submitted>September 13, 2023</last_update_submitted>
    <last_update_submitted_qc>September 13, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Fudan University</investigator_affiliation>
      <investigator_full_name>Peng Wang</investigator_full_name>
      <investigator_title>Clinical Professor</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Lenvatinib</mesh_term>
      <mesh_term>Tislelizumab</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/NCT06032845
  org study id: 2306276-5
  nct id: NCT06032845
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The objective of this study is to evaluate the efficacy and safety of cryoablation combined
        with Tislelizumab plus Lenvatinib for patients with previously treated solid tumors.
  Recent studies have suggested that local destruction of tumor tissue by cryoablation induced
        activation and maturation of dendritic cells and tumor-specific T cells by cross-presentation
        of tumor antigens. While pd-1 blocking antibody interferes with PD-1 mediated T-cell
        regulatory signaling. And combination of pd-1 blocking antibody plus lenvatinib showed
        increased ORR in many types of human cancers. Therefore, the objective of this study is to
        evaluate the efficacy and safety of cryoablation combined with Tislelizumab plus Lenvatinib
        in previously treated solid tumors.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: cryoablation, Tislelizumab, Lenvatinib
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Objective Response Rate (ORR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
  time frame: max 24 months
  description: ORR is defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by investigator.
  measure: Duration of Response (DOR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
  time frame: max 24 months
  description: DOR is defined as the time from first documented complete or partial response until disease progression, death from any cause, or censoring at date of last tumor assessment.
  measure: Progression Free Survival (PFS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
  time frame: max 24 months
  description: PFS is defined as the time from study treatment to disease progression or all-cause death as assessed by the investigator (whichever occurs first)
  measure: Overall survival (OS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
  time frame: max 24 months
  description: OS is defined as the time from study treatment to the date of death of the subject, regardless of the cause of death.
  measure: Disease control rate (DCR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
  time frame: max 24 months
  description: DCR is defined as the proportion of patients with complete response (CR), partial response (PR) and stable disease (SD)
  measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
  time frame: max 42 months
  description: An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience at least one AE will be reported.
  arm group label: Cryoablation combined with Tislelizumab and lenvatinib
  arm group type: Experimental
  description: Cryoablation treatment starts at day 0. Tislelizumab and Lenvatinib will be initiated on day 1 after cryoablation. Tislelizumab will be administered at 200 mg i.v. every 3 weeks until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent. Lenvatinib will be administered (bodyweight ≥ 60 kg, 12 mg; < 60 kg, 8 mg) orally daily every 3 weeks until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
  intervention type: Drug
  intervention name: Tislelizumab
  description: a PD-1 immune check inhibitor
  arm group label: Cryoablation combined with Tislelizumab and lenvatinib
  intervention type: Drug
  intervention name: Lenvatinib
  description: Lenvatinib capsules
  arm group label: Cryoablation combined with Tislelizumab and lenvatinib
  intervention type: Procedure
  intervention name: Cryoablation
  description: Cryoablation is performed under US or CT guidance per Investigator decision.
  arm group label: Cryoablation combined with Tislelizumab and lenvatinib
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Peng Wang, MD
  phone: 86-21-64175590
  email: wangp413@163.com
  last name: Peng Wang, MD
  phone: 86-21-64175590
  email: peng_wang@fudan.edu.cn
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Fudan University
  investigator full name: Peng Wang
  investigator title: Clinical Professor
  mesh term: Neoplasms
  mesh term: Lenvatinib
  mesh term: Tislelizumab