<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/NCT03792542</url>
  </required_header>
  <id_info>
    <org_study_id>ALTER-S003</org_study_id>
    <nct_id>NCT03792542</nct_id>
  </id_info>
  <brief_title>Anlotinib Hydrochloride For Advanced Soft Tissue Sarcoma Patients Who Do Not Receive Chemotherapy</brief_title>
  <official_title>Anlotinib Hydrochloride for Advanced Soft Tissue Sarcoma Patients Who do Not Receive Chemotherapy:a One-arm, Multi-center, Prospective Clinical Trial(ALTER-S003)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Second Affiliated Hospital, School of Medicine, Zhejiang University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Zhejiang Cancer Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ningbo No.2 Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hangzhou Third Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Jiangsu Provincial People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Jiangsu Cancer Institute &amp; Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Second Affiliated Hospital, School of Medicine, Zhejiang University</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>
      Anlotinib is a multi-target receptor tyrosine kinase inhibitor. It can inhibit the&#xD;
      angiogenesis related kinase, such as Vascular Endothelial Growth Factor Receptor (VEGFR),&#xD;
      Fibroblast Growth Factor Receptor(FGFR), Platelet-Derived Growth Factor Receptor(PDGFR), and&#xD;
      tumor cell proliferation related kinase c-Kit kinase. Anlotinib is an efficient second line&#xD;
      therapeutic agent in treatment for metastatic soft tissue sarcoma which has been approved in&#xD;
      clinical trials (ALTER-0203). There is a sort of patients who are not candidate for standard&#xD;
      first line chemotherapy that is doxorubicin based. The patients either refused or too old and&#xD;
      and debilitated to receive the cytotoxic chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is planned to be carried out in Zhejiang and Jiangsu province regional&#xD;
      multi-center. 44 cases are preliminarily expected to be included. The study started in&#xD;
      January 2019 and ended in December 2019. It is expected that the trial will end in December&#xD;
      2020.&#xD;
&#xD;
      In the absence of such situations as withdrawal of informed consent, intolerance of drug&#xD;
      toxicity and side effects, or inappropriateness for further trials, each participant's&#xD;
      expected time for research and treatment will continue until radiographically confirmed tumor&#xD;
      progression occurs.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">January 2019</start_date>
  <completion_date type="Anticipated">December 2020</completion_date>
  <primary_completion_date type="Anticipated">December 2020</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>Progress free survival (PFS)</measure>
    <time_frame>until Progressive Disease(PD) or death(up to 24 months)</time_frame>
    <description>PFS defined as the time from first dose of study treatment until the first date of either objective disease progression or death due to any cause.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>From randomization until death (up to 24 months)</time_frame>
    <description>OS is defined as the time until death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>each 42 days up to intolerance the toxicity or PD (up to 24 months)</time_frame>
    <description>ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.prior to progression or any further therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>each 42 days up to intolerance the toxicity or PD (up to 24 months)</time_frame>
    <description>Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life score (QoL)</measure>
    <time_frame>each 42 days up to intolerance the toxicity or PD (up to 24 months)</time_frame>
    <description>use EORTC QLQ-C30(version 3) questionnaire to evaluate the quality of life.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">44</enrollment>
  <condition>Soft Tissue Sarcoma</condition>
  <arm_group>
    <arm_group_label>Anlotinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Anlotinib p.o, qd and it should be continued until disease progress or toxicity cannot be tolerated or patients withdraw consent</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anlotinib</intervention_name>
    <description>Anlotinib Hydrochloride ( 12mg, quaque die（QD）, PO, d1-14, 21 days per cycle), take once when limosis in the morning. If patients cannot suffer from adverse events(AEs), they can get declined dosage.</description>
    <arm_group_label>Anlotinib</arm_group_label>
    <other_name>AL3818</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed the informed consent form prior to patient entry;&#xD;
&#xD;
          -  ≥ 18 and ≤ 70 years of age , regardless of gender；ECOG :0-2;Expected Survival Time:&#xD;
             Over 3 months;&#xD;
&#xD;
          -  Histologically confirmed diagnosis of un-resectable or recurrent metastatic soft&#xD;
             tissue sarcoma, such as: leiomyosarcoma, synovial sarcoma, undifferentiated&#xD;
             pleomorphic sarcoma, liposarcoma and other sarcomas. The following histologies are&#xD;
             excluded: alveolar Soft tissue sarcoma, rhabdomyosarcoma, chondrosarcoma,&#xD;
             osteosarcoma, gastrointestinal stromal tumor, humeral cutaneous fibrosarcoma, Ewing&#xD;
             sarcoma/primary neuroectodermal tumor, inflammatory myofibroblastic sarcoma and&#xD;
             malignant mesothelioma.&#xD;
&#xD;
          -  Patients who have not treated with anti-tumor drugs, or it has been more than 6 months&#xD;
             after the end of adjuvant and neoadjuvant chemotherapy.&#xD;
&#xD;
          -  Refuse the firs-line chemotherapy or could not tolerate chemotherapy as determined by&#xD;
             treatment physician&#xD;
&#xD;
          -  Evaluable disease by imaging or physical exam or measurable disease defined as at&#xD;
             least one lesion that can be accurately measured according to RECIST version 1.1.&#xD;
&#xD;
          -  normal main organs function as defined below: Hemoglobin (Hb) ≥ 80g / L, Neutrophils&#xD;
             (ANC) ≥ 1.5 × 109 / L, Platelet count (PLT) ≥ 80 × 109 / L, Serum creatinine (Cr) ≤&#xD;
             1.5 × normal upper limit (ULN) or creatinine clearance (CCr) ≥ 60ml / min, Blood urea&#xD;
             nitrogen (BUN) ≤ 2.5 × normal upper limit (ULN); Total bilirubin (TB) ≤ 1.5 × ULN;&#xD;
             Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; If&#xD;
             accompanied by liver metastases, ALT and AST ≤ 5 × ULN Albumin (ALB) ≥ 25 g/L. Doppler&#xD;
             ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ normal low limit&#xD;
             (50%)&#xD;
&#xD;
          -  Women of childbearing potential should agree to use and utilize an adequate method of&#xD;
             contraception (such as intrauterine device，contraceptive and condom) throughout&#xD;
             treatment and for at least 6 months after study is stopped；the result of serum or&#xD;
             urine pregnancy test should be negative within 7 days prior to study enrollment，and&#xD;
             the patients required to be non-lactating；Man participants should agree to use and&#xD;
             utilize an adequate method of contraception throughout treatment and for at least 6&#xD;
             months after study is stopped.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Appropriate and willing for cytotoxic chemotherapy.&#xD;
&#xD;
          -  Prior systemic therapy for this type of sarcoma. Neoadjuvant or adjuvant therapy more&#xD;
             than 6 months prior would not apply.&#xD;
&#xD;
          -  Prior treatment with any VEGFR tyrosine kinase inhibitor(such as sunitinib, sorafenib,&#xD;
             bevacizumab, imatinib, famitinib, apatinib, regorafenib and other drugs).&#xD;
&#xD;
          -  Systemic anti-tumor therapy, including cytotoxic therapy, signal transduction&#xD;
             inhibitors, and immunotherapy, is planned for the first 4 weeks prior to enrollment or&#xD;
             during the study. Radiation radiotherapy (EF-RT) was performed within 4 weeks prior to&#xD;
             enrollment.&#xD;
&#xD;
          -  A history of other malignancy ≤ 5 years previous with the exception of cured cervical&#xD;
             carcinoma in situ, cutaneous basal cell carcinoma or squamous cell carcinoma of the&#xD;
             skin.&#xD;
&#xD;
          -  Known brain metastases.&#xD;
&#xD;
          -  The investigator judged that during the follow-up study, the tumor is very likely to&#xD;
             invade the important blood vessels and cause fatal hemorrhage, or the formation of&#xD;
             tumor thrombosis with large veins (iliac vessels, inferior vena cava, pulmonary veins,&#xD;
             superior vena cava);&#xD;
&#xD;
          -  unable to swallow and retain oral capsules.&#xD;
&#xD;
          -  with any severe and/or uncontrolled disease, including:1)Uncontrollable hypertension&#xD;
             (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, despite&#xD;
             optimal drug treatment).2)Arrhythmias with grade II and above myocardial ischemia or&#xD;
             myocardial infarction, poor control (including corrected QT interval(QTc) men ≥ 450&#xD;
             ms, women ≥ 470 ms) and ≥ 2 congestive heart failure (New York Heart Association (&#xD;
             NYHA) rating).3)Poor control of diabetes (fasting blood glucose &gt; 10mmol / L).4)Active&#xD;
             or uncontrolled serious infection (≥ Common Terminology Criteria for Adverse Event(CTC&#xD;
             AE) grade 2 infection);5)Patients with active hepatitis B or hepatitis C (hepatitis B:&#xD;
             HBsAg-positive and hepatitis B virus(HBV) DNA ≥ 500 IU/mL; hepatitis C: hepatitis C&#xD;
             virus(HCV) RNA-positive and abnormal liver function), or active infection requiring&#xD;
             antimicrobial treatment (eg Treated with antibacterial drugs, antiviral drugs,&#xD;
             antifungal drugs);6)renal insufficiency: urine routine indicates urinary protein ≥ ++,&#xD;
             or confirmed 24-hour urine protein ≥ 1.0 g;7)Patients with seizures and need treatment&#xD;
&#xD;
          -  Abnormal coagulation (INR &gt; 1.5 or prothrombin time (PT) &gt; ULN + 4 seconds or&#xD;
             activated partial thromboplastin time(APTT) &gt; 1.5 ULN), with bleeding tendency or&#xD;
             undergoing thrombolytic or anticoagulant therapy.&#xD;
&#xD;
          -  Patients treated with anticoagulants or vitamin K antagonists such as warfarin,&#xD;
             heparin.&#xD;
&#xD;
          -  significant coughing blood in the 2 months before enrollment, or daily hemoptysis of&#xD;
             2.5ml or more.&#xD;
&#xD;
          -  history of psychotropic substance abuse who are unable to quit or have a mental&#xD;
             disorder.&#xD;
&#xD;
          -  Tendencies of hereditary or acquired hemorrhagic and thrombotic (such as hemophilia&#xD;
             patients, coagulopathy, thrombocytopenia, hypersplenism, etc.)&#xD;
&#xD;
          -  Any major unhealed wound, ulcer, or fracture occurred in a patient who had undergone&#xD;
             major surgery or trauma within 4 weeks and/or had any bleeding or bleeding episodes&#xD;
             which the degree is bigger than CTCAE 3 grade within 4 weeks prior to enrollment.&#xD;
&#xD;
          -  Active period digestive ulcers.&#xD;
&#xD;
          -  Cavity sinus or perforation occurred within 6 months.&#xD;
&#xD;
          -  Participated in other anti-tumor clinical trials within 4 weeks.&#xD;
&#xD;
          -  Received a potent CYP3A4 inhibitor (such as ketoconazole, itraconazole, erythromycin,&#xD;
             and clarithromycin) within 7 days, or received a potent CYP3A4 inducer within 12 days&#xD;
             prior to the study (eg. catarrh Treatment with imipramine, rifampicin and&#xD;
             phenobarbital).&#xD;
&#xD;
          -  Allergic reactions, hypersensitivity reactions or intolerance to anlotinib&#xD;
             hydrochloride or its excipients.&#xD;
&#xD;
          -  Pregnancy or lactation.&#xD;
&#xD;
          -  The investigator believes that there are any conditions that may damage the subject or&#xD;
             result in the subject not being able to meet or perform the research request.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zhaoming Ye, professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Second Affiliated Hospital, School of Medicine, Zhejiang University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Zhaoming Ye, professor</last_name>
    <phone>0086 13606501549</phone>
    <email>yezhaoming@zju.edu.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>The Second Affiliated Hospital of Zhejiang University School of Medicine</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <country>China</country>
      </address>
    </facility>
    <contact>
      <last_name>Zhaoming Ye, M.D.</last_name>
      <phone>0086 13606501549</phone>
      <email>yezhaoming@zju.edu.cn</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>January 2, 2019</study_first_submitted>
  <study_first_submitted_qc>January 2, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 3, 2019</study_first_posted>
  <last_update_submitted>January 2, 2019</last_update_submitted>
  <last_update_submitted_qc>January 2, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 3, 2019</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>Sarcoma</mesh_term>
  </condition_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/NCT03792542
org study id: ALTER-S003
nct id: NCT03792542
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Anlotinib is a multi-target receptor tyrosine kinase inhibitor. It can inhibit the
      angiogenesis related kinase, such as Vascular Endothelial Growth Factor Receptor (VEGFR),
      Fibroblast Growth Factor Receptor(FGFR), Platelet-Derived Growth Factor Receptor(PDGFR), and
      tumor cell proliferation related kinase c-Kit kinase. Anlotinib is an efficient second line
      therapeutic agent in treatment for metastatic soft tissue sarcoma which has been approved in
      clinical trials (ALTER-0203). There is a sort of patients who are not candidate for standard
      first line chemotherapy that is doxorubicin based. The patients either refused or too old and
      and debilitated to receive the cytotoxic chemotherapy.
This study is planned to be carried out in Zhejiang and Jiangsu province regional
      multi-center. 44 cases are preliminarily expected to be included. The study started in
      January 2019 and ended in December 2019. It is expected that the trial will end in December
      2020.

      In the absence of such situations as withdrawal of informed consent, intolerance of drug
      toxicity and side effects, or inappropriateness for further trials, each participant's
      expected time for research and treatment will continue until radiographically confirmed tumor
      progression occurs.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progress free survival (PFS)
time frame: until Progressive Disease(PD) or death(up to 24 months)
description: PFS defined as the time from first dose of study treatment until the first date of either objective disease progression or death due to any cause.
measure: Overall Survival (OS)
time frame: From randomization until death (up to 24 months)
description: OS is defined as the time until death due to any cause.
measure: Objective Response Rate (ORR)
time frame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
description: ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.prior to progression or any further therapy.
measure: Disease Control Rate (DCR)
time frame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
description: Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.
measure: Quality of Life score (QoL)
time frame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
description: use EORTC QLQ-C30(version 3) questionnaire to evaluate the quality of life.
arm group label: Anlotinib
arm group type: Experimental
description: Anlotinib p.o, qd and it should be continued until disease progress or toxicity cannot be tolerated or patients withdraw consent
intervention type: Drug
intervention name: Anlotinib
description: Anlotinib Hydrochloride ( 12mg, quaque die（QD）, PO, d1-14, 21 days per cycle), take once when limosis in the morning. If patients cannot suffer from adverse events(AEs), they can get declined dosage.
arm group label: Anlotinib
other name: AL3818
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Zhaoming Ye, professor
role: Principal Investigator
affiliation: Second Affiliated Hospital, School of Medicine, Zhejiang University
last name: Zhaoming Ye, professor
phone: 0086 13606501549
email: yezhaoming@zju.edu.cn
facility: 
contact: 
country: China
responsible party type: Sponsor
mesh term: Sarcoma