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/NCT06015061</url>
    </required_header>
    <id_info>
      <org_study_id>06086-04</org_study_id>
      <nct_id>NCT06015061</nct_id>
    </id_info>
    <brief_title>Prediction and Evaluation of Anlotinib Treatment Response Using Contrast Enhanced Ultrasound PPGL Patients</brief_title>
    <official_title>Prediction and Evaluation of Anlotinib Treatment Response Using Contrast Enhanced Ultrasound in Patients With Pheochromocytoma or Paraganglioma</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>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Anlotinib is a multi-target receptor tyrosine kinase inhibitor (TKI) targeting tumor&#xD;
        angiogenesis and growth. The purpose of this study is to evaluate the efficiency of contrast&#xD;
        enhanced ultrasound in assessing effectiveness of anlotinib in patients with locally&#xD;
        advanced, metastatic, or unresectable pheochromocytoma or paraganglioma(PPGL).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Contrast-enhanced ultrasound (CEUS) is a non-invasive and efficient imaging technique which&#xD;
        can observe the blood flow at the tissue perfusion level with microbubble contrast agents and&#xD;
        obtain information about tumor perfusion. There have been several studies demonstrating the&#xD;
        utility of CEUS for early prediction of response to neoadjuvant chemotherapy in breast&#xD;
        cancer, pancrearic cancer as well as lymphoma. However, few studies have reported the use of&#xD;
        CEUS for the evaluation of therapeutic response in PPGL. What quantitative parameters of CEUS&#xD;
        can early reflect the neovascular changes after treatment with anlotinib in patients with&#xD;
        locally advanced, metastatic, or unresectable PPGL? The aim of our study is to evaluate the&#xD;
        parameters for CEUS imaging and the therapeutic response of PPGL before and after anlotinib&#xD;
        therapy and to determine the most useful CEUS response parameters.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">March 1, 2023</start_date>
    <completion_date type="Anticipated">March 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">March 1, 2025</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Evaluate if tumor uptake of contrast agent is predictive of response to anlotinib therapy measured by comparison of Peak Intensity (PI) at CEUS imaging prior to and after therapy.</measure>
      <time_frame>Baseline and after 1-2 cycles(each cycle is 21 days)</time_frame>
      <description>Before initiation of the therapy and during anlotinib therapy, patients would receive CEUS examination. The dynamic CEUS images of each lesion were analysed with the aid of time intensity curves (TICs) drawn by QLAB software (Philips Healthcare, Andover, MA). PI measurements will be compared to clinical measurement of response to treatment taking into consideration standard response criteria including radiological imaging, biochemical (catecholamine levels) response.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Evaluate if the time to peak (TTP) is predictive of response to anlotinib therapy measured by comparison of TTP at CEUS imaging prior to and after therapy.</measure>
      <time_frame>Baseline and after 1-2 cycles(each cycle is 21days)</time_frame>
      <description>Before initiation of the therapy and during anlotinib therapy, patients would receive CEUS examination. The dynamic CEUS images of each lesion were analysed with the aid of time intensity curves (TICs) drawn by QLAB software (Philips Healthcare, Andover, MA). TTP measurements will be compared to clinical measurement of response to treatment taking into consideration standard response criteria.</description>
    </primary_outcome>
    <number_of_groups>1</number_of_groups>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Pheochromocytoma, Metastatic</condition>
    <condition>Ultrasonography</condition>
    <condition>Paraganglioma, Malignant</condition>
    <condition>Pheochromocytoma Malignant</condition>
    <arm_group>
      <arm_group_label>Pheochromocytoma or Paraganglioma Patients with Anlotinib Treatment</arm_group_label>
      <description>to evaluate the efficiency of contrast enhanced ultrasound in assessing effectiveness of anlotinib in patients with locally advanced, metastatic, or unresectable pheochromocytoma or paraganglioma(PPGL).</description>
    </arm_group>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Contrast-enhanced ultrasound(CEUS)</intervention_name>
      <description>CEUS is a quantitative kinetic imaging modality that can assess intravascular blood flow in PPGL tumors.</description>
      <arm_group_label>Pheochromocytoma or Paraganglioma Patients with Anlotinib Treatment</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          in patients with locally advanced, metastatic, or unresectable pheochromocytoma or&#xD;
          paraganglioma.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  18 years of age or older.&#xD;
  &#xD;
            -  Provide written informed consent.&#xD;
  &#xD;
            -  Willing to return to enrolling institution for follow-up.&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.&#xD;
  &#xD;
            -  Life expectancy &gt; 3 months.&#xD;
  &#xD;
            -  Patients diagnosis with pheochromocytoma or paraganglioma will received anlotinib&#xD;
               treatment.&#xD;
  &#xD;
            -  Laboratory requirements:&#xD;
  &#xD;
                 -  Absolute granulocyte count (AGC) greater than 1.5 x 109/L;&#xD;
  &#xD;
                 -  Platelet count greater than 80 x 109/L;&#xD;
  &#xD;
                 -  Hemoglobin greater than 90g/L;&#xD;
  &#xD;
                 -  Serum bilirubin less than 1.5 x upper limit of normal (ULN);&#xD;
  &#xD;
                 -  Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less&#xD;
                    than 2.5 x ULN;&#xD;
  &#xD;
                 -  Serum creatinine less than 1.5 x ULN or creatinine clearance (CCr)≥60ml/min;&#xD;
  &#xD;
                 -  Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ lower&#xD;
                    limit of normal value (50%).&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients who are allergic to ultrasound contrast agents.&#xD;
  &#xD;
            -  Any of the following:Pregnant women,Nursing women,Men or women of childbearing&#xD;
               potential who are unwilling to employ adequate contraception.&#xD;
  &#xD;
            -  Patients who have previously used other anti-vascular targeted drugs, such as&#xD;
               sunitinib, bevacizumab, endurance, etc.&#xD;
  &#xD;
            -  Chemotherapy/systemic therapy, radiotherapy, immunotherapy or surgery within 4 weeks&#xD;
               prior to kinase inhibitor therapy.&#xD;
  &#xD;
            -  Patients with another primary malignancy within 5 years prior to starting study drug.&#xD;
  &#xD;
          Those who have multiple factors that affect oral medications (such as inability to swallow,&#xD;
          chronic diarrhea, intestinal obstruction, etc.).&#xD;
  &#xD;
            -  Patients with known untreated brain metastases are excluded. Patients having a history&#xD;
               of brain metastasis that have been previously irradiated or resected greater than 2&#xD;
               months prior to enrollment and are clinically and radiographically stable will be&#xD;
               considered for enrollment. Patients with brain metastases with symptoms or symptom&#xD;
               control for less than 2 months.&#xD;
  &#xD;
            -  Active or uncontrolled intercurrent illness including, but not limited to&#xD;
  &#xD;
                 -  Patients with unsatisfactory blood pressure control (systolic blood pressure ≥150&#xD;
                    mmHg, diastolic blood pressure ≥100 mmHg);&#xD;
  &#xD;
                 -  Patients with uncontrolled myocardial ischemia or myocardial infarction,&#xD;
                    arrhythmia (including QTC≥480ms), and uncontrolled congestive heart failure，grade&#xD;
                    ≥2（New York Heart Association )&#xD;
  &#xD;
                 -  ongoing or active infection;&#xD;
  &#xD;
                 -  Liver cirrhosis, decompensated liver disease, active hepatitis or chronic&#xD;
                    hepatitis require antiviral treatment;&#xD;
  &#xD;
                 -  Renal failure requires hemodialysis or peritoneal dialysis;&#xD;
  &#xD;
                 -  Have a history of immunodeficiency, including HIV or other acquired or congenital&#xD;
                    immunodeficiency diseases, or a history of organ transplantation;&#xD;
  &#xD;
                 -  Diabetes is poorly controlled (fasting blood glucose (FBG)&gt; 10mmol/L);&#xD;
  &#xD;
                 -  Urine routines suggest that urine protein is ≥++, and the 24-hour urine protein&#xD;
                    content is confirmed to be greater than 1.0 g;&#xD;
  &#xD;
                 -  Patients who have seizures and need treatment;&#xD;
  &#xD;
            -  Any of the following conditions =&lt; 6 months prior to registration: Cerebrovascular&#xD;
               accident (CVA) or transient ischemic attack (TIA); Serious or unstable cardiac&#xD;
               arrhythmia; Pulmonary embolism, untreated deep venous thrombosis (DVT).&#xD;
  &#xD;
          Received major surgical treatment, open biopsy or obvious traumatic injury within 28 days&#xD;
          before enrollment.&#xD;
  &#xD;
            -  Those who have a history of psychotropic drug abuse and cannot be quit or have mental&#xD;
               disorders.&#xD;
  &#xD;
            -  Imaging shows that the tumor has invaded important blood vessels or the investigator&#xD;
               judges that the tumor is very likely to invade important blood vessels and cause fatal&#xD;
               bleeding during the follow-up study.&#xD;
  &#xD;
            -  Regardless of the severity, patients with any signs of bleeding or medical history;&#xD;
               within 4 weeks before enrollment, patients with any bleeding or bleeding event ≥ CTCAE&#xD;
               grade 3, unhealed wounds, ulcers or fractures.&#xD;
  &#xD;
            -  Patients are using drugs that interact with Anlotinib.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>80 Years</maximum_age>
    </eligibility>
    <overall_official>
      <last_name>Anli Tong</last_name>
      <role>Principal Investigator</role>
      <affiliation>Peking Union Medical College Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Anli Tong</last_name>
      <phone>13911413589</phone>
      <email>tonganli@hotmail.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Peking Union Medical College Hospital</name>
        <address>
          <city>Beijing</city>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Anli Tong</last_name>
        <phone>13911413589</phone>
        <email>tonganli@hotmail.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <results_reference>
      <citation>Kim Y, Kim SH, Song BJ, Kang BJ, Yim KI, Lee A, Nam Y. Early Prediction of Response to Neoadjuvant Chemotherapy Using Dynamic Contrast-Enhanced MRI and Ultrasound in Breast Cancer. Korean J Radiol. 2018 Jul-Aug;19(4):682-691. doi: 10.3348/kjr.2018.19.4.682. Epub 2018 Jun 14.</citation>
      <PMID>29962874</PMID>
    </results_reference>
    <results_reference>
      <citation>Zhang Q, Wu L, Yang D, Qiu Y, Yu L, Dong Y, Wang WP. Clinical application of dynamic contrast enhanced ultrasound in monitoring the treatment response of chemoradiotherapy of pancreatic ductal adenocarcinoma. Clin Hemorheol Microcirc. 2020;75(3):325-334. doi: 10.3233/CH-190786.</citation>
      <PMID>31985457</PMID>
    </results_reference>
    <results_reference>
      <citation>Xin L, Yan Z, Zhang X, Zang Y, Ding Z, Xue H, Zhao C. Parameters for Contrast-Enhanced Ultrasound (CEUS) of Enlarged Superficial Lymph Nodes for the Evaluation of Therapeutic Response in Lymphoma: A Preliminary Study. Med Sci Monit. 2017 Nov 15;23:5430-5438. doi: 10.12659/msm.907293.</citation>
      <PMID>29138385</PMID>
    </results_reference>
    <verification_date>March 2023</verification_date>
    <study_first_submitted>May 22, 2023</study_first_submitted>
    <study_first_submitted_qc>August 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 29, 2023</study_first_posted>
    <last_update_submitted>August 28, 2023</last_update_submitted>
    <last_update_submitted_qc>August 28, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 29, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Pheochromocytoma</mesh_term>
      <mesh_term>Paraganglioma</mesh_term>
    </condition_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/NCT06015061
  org study id: 06086-04
  nct id: NCT06015061
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  Anlotinib is a multi-target receptor tyrosine kinase inhibitor (TKI) targeting tumor
        angiogenesis and growth. The purpose of this study is to evaluate the efficiency of contrast
        enhanced ultrasound in assessing effectiveness of anlotinib in patients with locally
        advanced, metastatic, or unresectable pheochromocytoma or paraganglioma(PPGL).
  Contrast-enhanced ultrasound (CEUS) is a non-invasive and efficient imaging technique which
        can observe the blood flow at the tissue perfusion level with microbubble contrast agents and
        obtain information about tumor perfusion. There have been several studies demonstrating the
        utility of CEUS for early prediction of response to neoadjuvant chemotherapy in breast
        cancer, pancrearic cancer as well as lymphoma. However, few studies have reported the use of
        CEUS for the evaluation of therapeutic response in PPGL. What quantitative parameters of CEUS
        can early reflect the neovascular changes after treatment with anlotinib in patients with
        locally advanced, metastatic, or unresectable PPGL? The aim of our study is to evaluate the
        parameters for CEUS imaging and the therapeutic response of PPGL before and after anlotinib
        therapy and to determine the most useful CEUS response parameters.
  observational model: Cohort
  time perspective: Prospective
  measure: Evaluate if tumor uptake of contrast agent is predictive of response to anlotinib therapy measured by comparison of Peak Intensity (PI) at CEUS imaging prior to and after therapy.
  time frame: Baseline and after 1-2 cycles(each cycle is 21 days)
  description: Before initiation of the therapy and during anlotinib therapy, patients would receive CEUS examination. The dynamic CEUS images of each lesion were analysed with the aid of time intensity curves (TICs) drawn by QLAB software (Philips Healthcare, Andover, MA). PI measurements will be compared to clinical measurement of response to treatment taking into consideration standard response criteria including radiological imaging, biochemical (catecholamine levels) response.
  measure: Evaluate if the time to peak (TTP) is predictive of response to anlotinib therapy measured by comparison of TTP at CEUS imaging prior to and after therapy.
  time frame: Baseline and after 1-2 cycles(each cycle is 21days)
  description: Before initiation of the therapy and during anlotinib therapy, patients would receive CEUS examination. The dynamic CEUS images of each lesion were analysed with the aid of time intensity curves (TICs) drawn by QLAB software (Philips Healthcare, Andover, MA). TTP measurements will be compared to clinical measurement of response to treatment taking into consideration standard response criteria.
  arm group label: Pheochromocytoma or Paraganglioma Patients with Anlotinib Treatment
  description: to evaluate the efficiency of contrast enhanced ultrasound in assessing effectiveness of anlotinib in patients with locally advanced, metastatic, or unresectable pheochromocytoma or paraganglioma(PPGL).
  intervention type: Diagnostic Test
  intervention name: Contrast-enhanced ultrasound(CEUS)
  description: CEUS is a quantitative kinetic imaging modality that can assess intravascular blood flow in PPGL tumors.
  arm group label: Pheochromocytoma or Paraganglioma Patients with Anlotinib Treatment
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 80 Years
  last name: Anli Tong
  role: Principal Investigator
  affiliation: Peking Union Medical College Hospital
  last name: Anli Tong
  phone: 13911413589
  email: tonganli@hotmail.com
  facility: 
  status: Recruiting
  contact: 
  country: China
  citation: Kim Y, Kim SH, Song BJ, Kang BJ, Yim KI, Lee A, Nam Y. Early Prediction of Response to Neoadjuvant Chemotherapy Using Dynamic Contrast-Enhanced MRI and Ultrasound in Breast Cancer. Korean J Radiol. 2018 Jul-Aug;19(4):682-691. doi: 10.3348/kjr.2018.19.4.682. Epub 2018 Jun 14.
  PMID: 29962874
  citation: Zhang Q, Wu L, Yang D, Qiu Y, Yu L, Dong Y, Wang WP. Clinical application of dynamic contrast enhanced ultrasound in monitoring the treatment response of chemoradiotherapy of pancreatic ductal adenocarcinoma. Clin Hemorheol Microcirc. 2020;75(3):325-334. doi: 10.3233/CH-190786.
  PMID: 31985457
  citation: Xin L, Yan Z, Zhang X, Zang Y, Ding Z, Xue H, Zhao C. Parameters for Contrast-Enhanced Ultrasound (CEUS) of Enlarged Superficial Lymph Nodes for the Evaluation of Therapeutic Response in Lymphoma: A Preliminary Study. Med Sci Monit. 2017 Nov 15;23:5430-5438. doi: 10.12659/msm.907293.
  PMID: 29138385
  responsible party type: Sponsor
  mesh term: Pheochromocytoma
  mesh term: Paraganglioma
  sharing ipd: No