<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/NCT04409223</url>
  </required_header>
  <id_info>
    <org_study_id>SHR-1020-Ⅲ-303</org_study_id>
    <nct_id>NCT04409223</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Famitinib Versus Sunitinib in the Treatment of Advanced Gastrointestinal Stromal Tumour Patients After Failure of Imatinib</brief_title>
  <official_title>A Phase III, Open Label, Randomised，Controlled, Multi-centre Study to Assess the Efficacy and Safety of Famitinib Versus Sunitinib in the Treatment of Advanced Gastrointestinal Stromal Tumour Patients After Failure of Imatinib</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jiangsu HengRui Medicine Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Jiangsu HengRui Medicine Co., Ltd.</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 study is being conducted to evaluate the efficacy and safety of famitinib in the&#xD;
      treatment of advanced gastrointestinal stromal tumour patients after failure of imatinib&#xD;
      compared to sunitinib.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 12, 2020</start_date>
  <completion_date type="Anticipated">December 2025</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>30 months</time_frame>
    <description>Progression-free survival (PFS) assessed by BIRC based on RECIST 1.1 criteria</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>30 months</time_frame>
    <description>Progression-free survival (PFS) assessed by BIRC based on mRECIST criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>30 months</time_frame>
    <description>Progression-free survival (PFS) assessed by researchers based on RECIST 1.1 criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>time to disease progression (TTP)</measure>
    <time_frame>30 months</time_frame>
    <description>Based on the RECIST v1.1 criteria, BIRC and the researchers' evaluation of: time to disease progression (TTP)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to treatment failure (TTF)</measure>
    <time_frame>30 months</time_frame>
    <description>Based on the RECIST v1.1 criteria, BIRC and the researchers' evaluation of: Time to treatment failure (TTF);</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>30 months</time_frame>
    <description>Based on the RECIST v1.1 criteria, BIRC and the researchers' evaluation of: Objective response rate (ORR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR)</measure>
    <time_frame>30 months</time_frame>
    <description>Based on the RECIST v1.1 criteria, BIRC and the researchers' evaluation of: Duration of Response (DOR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rates (DCR)</measure>
    <time_frame>30 months</time_frame>
    <description>Based on the RECIST v1.1 criteria, BIRC and the researchers' evaluation of: Disease control rates (DCR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall survival (OS)</measure>
    <time_frame>30 months</time_frame>
    <description>Based on the RECIST v1.1 criteria, BIRC and the researchers' evaluation of: overall survival (OS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events and Serious Adverse Events</measure>
    <time_frame>30 months</time_frame>
    <description>Adverse Events and Serious Adverse Events</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">304</enrollment>
  <condition>Gastrointestinal Stromal Tumors</condition>
  <arm_group>
    <arm_group_label>Famitinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Sunitinib</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Famitinib capsules</intervention_name>
    <description>Oral KIT/PDGFRA kinase inhibitor</description>
    <arm_group_label>Famitinib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sunitinib Capsules</intervention_name>
    <description>Oral receptor tyrosine kinase (RTK) inhibitor</description>
    <arm_group_label>Sunitinib</arm_group_label>
    <other_name>Sutent</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. The patients were enrolled voluntarily and signed informed consent, with good&#xD;
             compliance and follow-up&#xD;
&#xD;
          2. Age ≥18 years (on the date of signing informed consent), for both men and women&#xD;
&#xD;
          3. Histologically confirmed metastatic or untreatable gastrointestinal stromal tumors&#xD;
             have at least one measurable lesion that meets the criteria of RECIST v1.1. Lesions&#xD;
             that have undergone radiotherapy must be confirmed by imaging to show progression&#xD;
             after radiotherapy&#xD;
&#xD;
          4. Previous treatment with imatinib and eventual treatment failure (disease progression&#xD;
             or toxicity intolerance during treatment)&#xD;
&#xD;
          5. The subjects were able to provide 10 ml blood samples and fresh or archived tumor&#xD;
             tissue, or to receive biopsy at baseline for biomarker analysis.&#xD;
&#xD;
             Note: if there is no archived tumor tissue sample, those at high risk of receiving&#xD;
             biopsy after assessment by the researcher, who can provide the previous c-kit /PDGFRA&#xD;
             test report, may also be selected for inclusion.&#xD;
&#xD;
          6. Eastern Cooperative Oncology Group performance status of 1 or lower&#xD;
&#xD;
          7. Expected survival ≥12 weeks&#xD;
&#xD;
          8. Vital organs and body functions meet the following requirements (no blood products or&#xD;
             cell agents are allowed to be used within 14 days before the first use):&#xD;
&#xD;
             Neutrophil absolute count ≥1.5×109/L; Platelet ≥ 100×109/L; Hemoglobin ≥ 90 g/L;&#xD;
             Bilirubin ≤ 1.5×ULN; ALT and AST ≤2.5×ULN serum creatinine≤1.5×ULN; Results of urinary&#xD;
             protein &lt;2+; If urinary protein is ≥2+, 24-hour quantitative determination of urinary&#xD;
             protein should be conducted, and no more than 1g/24 hour is qualified. Serum calcium,&#xD;
             potassium, magnesium and phosphorus are within the normal range or have been corrected&#xD;
             to the normal range before randomization. International standardized ratio INR≤ 1.5&#xD;
             and activated partial thromboplastin time APTT≤1.5×ULN; QTc≤ 450 ms (male), 470 ms&#xD;
             (female); Left ventricular ejection fraction LVEF≥50%.&#xD;
&#xD;
          9. Use of a medically approved contraceptive method (e.g., intrauterine contraceptive&#xD;
             device, contraceptive pill or condom) during the study period and within 90 days after&#xD;
             the end of the study period for female patients of non-surgical sterilization or&#xD;
             childbearing age; The serum HCG of female patients of childbearing age without&#xD;
             surgical sterilization must be negative within 72 hours before randomization, and must&#xD;
             be non-lactating to be enrolled; For male patients whose partners are women of&#xD;
             childbearing age, effective methods of contraception should be used during the study&#xD;
             period and within 90 days after the end of the study period.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previously received molecular targeted therapy for gastrointestinal stromal tumor&#xD;
             except imatinib&#xD;
&#xD;
          2. The toxicity of previous imatinib or other treatments has not recovered or reached NCI&#xD;
             CTC AE 5.0≤ 1&#xD;
&#xD;
          3. For patients with clinical symptoms of ascites or pleural effusion, those requiring&#xD;
             puncture drainage or those who had received thoracic or ascites drainage within 1&#xD;
             month before signing informed consent were excluded, those with only small amount of&#xD;
             ascites or pleural effusion on imaging but no clinical symptoms are qualified.&#xD;
&#xD;
          4. A second primary malignancy occurred within the last 5 years, except for adequately&#xD;
             treated basal cell carcinoma, cutaneous squamous cell carcinoma, or carcinoma in situ&#xD;
             of the cervix&#xD;
&#xD;
          5. Gastrointestinal stromal tumor with central nervous system metastasis&#xD;
&#xD;
          6. Inability to swallow, chronic diarrhea, intestinal obstruction, or factors that affect&#xD;
             drug use and absorption&#xD;
&#xD;
          7. Bleeding≥ grade 2 occurred in the first 4 weeks of randomization (NCI, CTC, AE 5.0)&#xD;
&#xD;
          8. Symptoms occurred within 12 months before randomization: myocardial infarction,&#xD;
             severe/unstable angina pectoris, coronary/peripheral artery bypass grafting,&#xD;
             symptomatic congestive heart failure, cerebrovascular accident or transient ischemic&#xD;
             attack, or an arteriovenous embolism event (e.g., deep venous embolism of lower&#xD;
             extremities, pulmonary embolism) within 6 months&#xD;
&#xD;
          9. There are clinical symptoms or diseases of the heart that are not well controlled,&#xD;
             such as (1) heart failure above NYHA grade 2 (2) unstable angina (3) myocardial&#xD;
             infarction within 1 year (4) clinically significant supraventricular or ventricular&#xD;
             arrhythmia requiring treatment or intervention&#xD;
&#xD;
         10. Have hypertension, and cannot be well controlled by antihypertensive medication&#xD;
             (systolic blood pressure ≥ 140mmhg or diastolic blood pressure ≥ 90mmhg, if the blood&#xD;
             pressure was abnormal during the screening period, 2 consistent measurements must be&#xD;
             done with an interval of more than 24h after medical correction); Previous&#xD;
             hypertensive crisis or hypertensive encephalopathy;&#xD;
&#xD;
         11. Drug uncontrollable thyroid dysfunction&#xD;
&#xD;
         12. Known acute or chronic active hepatitis, HBV virus titer &gt; 500 IU, HCV RNA detection &gt;&#xD;
             ULN&#xD;
&#xD;
         13. History of immunodeficiency, including HIV positive, acquired or congenital&#xD;
             immunodeficiency disorder, or a history of organ transplantation&#xD;
&#xD;
         14. Major surgery or radiotherapy within the first 4 weeks of randomization, or temporary&#xD;
             palliative radiotherapy for pain relief within the first 1 week of randomization;&#xD;
             Molecular-targeted therapy (including oral targeted drugs in other clinical trials) is&#xD;
             less than 5 drug half-lives away form randomization date&#xD;
&#xD;
         15. Participated in clinical trials of other drugs in the first 4 weeks of randomization&#xD;
&#xD;
         16. Digestive tract perforation occurred 3 months before randomization&#xD;
&#xD;
         17. In the judgment of the investigator, a concomitant illness (severe diabetes, a clear&#xD;
             history of neurological or mental disorders, e.g., epilepsy or dementia) that&#xD;
             seriously endangers the patient's safety or prevents the patient from completing the&#xD;
             study&#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_official>
    <last_name>Jianming Xu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Beijing 302 Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Quanren Wang, MD</last_name>
    <phone>(+86) 021-50118402</phone>
    <email>wangquanren@hrglobe.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>307 Hospital of PLA</name>
      <address>
        <city>Beijing</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>jianming xu, PHD</last_name>
      <email>jmxu2003@yahoo.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>May 27, 2020</study_first_submitted>
  <study_first_submitted_qc>May 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 1, 2020</study_first_posted>
  <last_update_submitted>November 30, 2020</last_update_submitted>
  <last_update_submitted_qc>November 30, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 1, 2020</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>Gastrointestinal Stromal Tumors</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sunitinib</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT04409223
org study id: SHR-1020-Ⅲ-303
nct id: NCT04409223
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The study is being conducted to evaluate the efficacy and safety of famitinib in the
      treatment of advanced gastrointestinal stromal tumour patients after failure of imatinib
      compared to sunitinib.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free survival (PFS)
time frame: 30 months
description: Progression-free survival (PFS) assessed by BIRC based on RECIST 1.1 criteria
measure: Progression-free survival (PFS)
time frame: 30 months
description: Progression-free survival (PFS) assessed by BIRC based on mRECIST criteria
measure: Progression-free survival (PFS)
time frame: 30 months
description: Progression-free survival (PFS) assessed by researchers based on RECIST 1.1 criteria
measure: time to disease progression (TTP)
time frame: 30 months
description: Based on the RECIST v1.1 criteria, BIRC and the researchers' evaluation of: time to disease progression (TTP)
measure: Time to treatment failure (TTF)
time frame: 30 months
description: Based on the RECIST v1.1 criteria, BIRC and the researchers' evaluation of: Time to treatment failure (TTF);
measure: Objective response rate (ORR)
time frame: 30 months
description: Based on the RECIST v1.1 criteria, BIRC and the researchers' evaluation of: Objective response rate (ORR)
measure: Duration of Response (DOR)
time frame: 30 months
description: Based on the RECIST v1.1 criteria, BIRC and the researchers' evaluation of: Duration of Response (DOR)
measure: Disease control rates (DCR)
time frame: 30 months
description: Based on the RECIST v1.1 criteria, BIRC and the researchers' evaluation of: Disease control rates (DCR)
measure: overall survival (OS)
time frame: 30 months
description: Based on the RECIST v1.1 criteria, BIRC and the researchers' evaluation of: overall survival (OS)
measure: Adverse Events and Serious Adverse Events
time frame: 30 months
description: Adverse Events and Serious Adverse Events
arm group label: Famitinib
arm group type: Experimental
arm group label: Sunitinib
arm group type: Active Comparator
intervention type: Drug
intervention name: Famitinib capsules
description: Oral KIT/PDGFRA kinase inhibitor
arm group label: Famitinib
intervention type: Drug
intervention name: Sunitinib Capsules
description: Oral receptor tyrosine kinase (RTK) inhibitor
arm group label: Sunitinib
other name: Sutent
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jianming Xu, MD
role: Principal Investigator
affiliation: Beijing 302 Hospital
last name: Quanren Wang, MD
phone: (+86) 021-50118402
email: wangquanren@hrglobe.cn
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Gastrointestinal Stromal Tumors
mesh term: Sunitinib