<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/NCT03799601</url>
  </required_header>
  <id_info>
    <org_study_id>TJCC-LC-20190108</org_study_id>
    <nct_id>NCT03799601</nct_id>
  </id_info>
  <brief_title>Docetaxel Combined With Carboplatin Plus Anlotinib as First Line Treatment in NSCLC</brief_title>
  <acronym>ALTER-L013</acronym>
  <official_title>A Single Arm, Multi-center Study to Assess the Efficacy and Safety of Docetaxel Combined With Carboplatin Plus Anlotinib as First Line Treatment in Non-squamous Non-small-cell Lung Cancer (NSCLC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tongji Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Chia Tai Tianqing Pharmaceutical Group Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Tongji 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 which has shown an affirmatory efficacy in ALTER0303 controlled trial as a 3rd-line&#xD;
      treatment on advanced NSCLC is a tyrosine kinase inhibitor with a favorable safety profile in&#xD;
      phase I trial which mainly targets VEGFR1/2/3, FGFR, PDGFR and c-kit. The purpose of this&#xD;
      trail is to establish whether advanced non-squamous NSCLC patients could benefit from the&#xD;
      combination treatment of docetaxel, carboplatin and anlotinib as the first-line and&#xD;
      maintenance treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      First-line patients (or postoperative recurrence) with locally advanced or metastatic NSCLC&#xD;
      were enrolled in this trail. The patients (clinical stage ⅢB/Ⅳ, with no sensitizing mutation&#xD;
      of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma&#xD;
      kinase gene) were confirmed by histological or cytological diagnosis. The primary endpoint is&#xD;
      PFS; secondary endpoint includes OS, DCR and ORR. The study was single-arm, conducted at 8&#xD;
      centers in China mainland. The primary end point was PFS (time from enrollment to first&#xD;
      RECIST1.1-defined PD or death). 45 patients were planned for enrollment. This estimate was&#xD;
      based on 80% power, with a two-sided 5% significance level. We analyzed PFS and OS using&#xD;
      Kaplan-Meier methodology. The research protocol was approved by the relevant ethics&#xD;
      committees, and the study was conducted according to the Declaration of Helsinki and Good&#xD;
      Clinical Practice guidelines. Patients gave written informed consent to participate in the&#xD;
      trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">March 1, 2019</start_date>
  <completion_date type="Anticipated">December 1, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2019</primary_completion_date>
  <phase>Phase 4</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>progression-free survival</measure>
    <time_frame>Estimated about 24 months.</time_frame>
    <description>Clinical response of treatment according to RESIST v1.1 criteria (PFS, progression-free survival)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Estimated about 24 months.</time_frame>
    <description>Clinical response of treatment according to RESIST v1.1 criteria (OS, overall survival)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate</measure>
    <time_frame>Estimated about 24 months.</time_frame>
    <description>Clinical response of treatment according to RESIST v1.1 criteria (DCR, disease control rate)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate</measure>
    <time_frame>Estimated about 24 months.</time_frame>
    <description>Clinical response of treatment according to RESIST v1.1 criteria (ORR, Overall Response Rate)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">45</enrollment>
  <condition>NSCLC</condition>
  <arm_group>
    <arm_group_label>combination of docetaxel, carboplatin and anlotinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anlotinib</intervention_name>
    <description>Anlotinib which has shown an affirmatory efficacy in ALTER0303 controlled trial as a 3rd-line treatment on advanced NSCLC is a tyrosine kinase inhibitor with a favorable safety profile in phase I trial which mainly targets VEGFR1/2/3, FGFR, PDGFR and c-kit.</description>
    <arm_group_label>combination of docetaxel, carboplatin and anlotinib</arm_group_label>
    <other_name>Anlotinib Hydrochloride</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Docetaxel</intervention_name>
    <description>a chemotherapy medication used to treat a number of types of cancer.This includes breast cancer, head and neck cancer, stomach cancer, prostate cancer and non-small-cell lung cancer.It may be used by itself or along with other chemotherapy medication.It is given by slow injection into a vein.</description>
    <arm_group_label>combination of docetaxel, carboplatin and anlotinib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>Carboplatin is used to treat a number of forms of cancer. This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. It may be used for some types of testicular cancer but cisplatin is generally more effective.</description>
    <arm_group_label>combination of docetaxel, carboplatin and anlotinib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ≥18 years of age on the day of signing informed consent and with good compliance and&#xD;
             agree to accept follow-up of disease progression and adverse events.&#xD;
&#xD;
          -  Patients with histologic or cytologic confirmation of advanced or metastatic Non&#xD;
             squamous NSCLC with stage IIIB or IV disease.（For recurrent patients, adjuvant&#xD;
             chemotherapy, neoadjuvant chemotherapy or neoadjuvant chemotherapy plus adjuvant were&#xD;
             assessed for eligibility, and the last treatment time must be more than 6 months&#xD;
             before enrollment）&#xD;
&#xD;
          -  There were at least one target lesions in the past three months has not yet accepted&#xD;
             radiotherapy, and could be recorded by magnetic resonance imaging (MRI) or computer&#xD;
             tomography (CT) measuring accurately at least in one direction(The maximum diameter&#xD;
             needs to be recorded), including conventional CT ≥20 mm or spiral CT ≥10 mm.&#xD;
&#xD;
          -  Life expectancy ≥6 months&#xD;
&#xD;
          -  a performance status of 0 or 2 on the Eastern Cooperative Oncology Group (ECOG)&#xD;
             Performance Status.&#xD;
&#xD;
          -  With normal marrow, liver ,renal and coagulation function:&#xD;
&#xD;
          -  The blood routine examination need to be standard (no blood transfusion and blood&#xD;
             products within 14 days, no g-csf and other hematopoietic stimulating factor&#xD;
             correction)&#xD;
&#xD;
          -  The main organs function are normally, the following criteria are met:(1)Blood routine&#xD;
             examination criteria should be met (no blood transfusion and blood products within 14&#xD;
             days, no correction by G-CSF and other hematopoietic stimuli): HB≥90 g/L; ANC ≥&#xD;
             1.5×10^9/L; PLT ≥80×10^9/L;(2)Biochemical examinations must meet the following&#xD;
             criteria: TBIL&lt;1.5×ULN; ALT and AST &lt; 2.5×ULN, and for patients with liver metastases&#xD;
             &lt; 5×ULN; Serum Cr ≤ 1.25×ULN or endogenous creatinine clearance &gt; 60 ml/min&#xD;
             (Cockcroft-Gault formula);&#xD;
&#xD;
          -  Women of child-bearing age should take appropriate contraceptive measures and should&#xD;
             not breastfeed from screening to 3 months after stopping the study and&#xD;
             treatment.Before starting administration, the pregnancy test was negative, or one of&#xD;
             the following criteria was met to prove that there was no risk of pregnancy:&#xD;
&#xD;
               1. Postmenopause is defined as amenorrhea at least 12 months after age 50 and&#xD;
                  cessation of all exogenous hormone replacement therapy;&#xD;
&#xD;
               2. Postmenopausal women under the age of 50 May also be considered postmenopausal if&#xD;
                  their amenorrhea is 12 months or more after the cessation of all exogenous&#xD;
                  hormone therapy and their luteinizing hormone (LH) and follicle-stimulating&#xD;
                  hormone (FSH) levels are within the reference value range of laboratory&#xD;
                  postmenopausal;&#xD;
&#xD;
               3. Have undergone irreversible sterilization surgery, including hysterectomy,&#xD;
                  bilateral ovectomy or bilateral salpingectomy, except for bilateral tubal&#xD;
                  ligation.&#xD;
&#xD;
          -  For men, consent is required to use appropriate methods of contraception or to be&#xD;
             surgically sterilized during the trial and 8 weeks after the last administration of&#xD;
             the trial drug.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Small cell lung cancer (including lung cancer mixed with small cell lung cancer and&#xD;
             non-small cell lung cancer), Lung sarcomatoid carcinoma;&#xD;
&#xD;
          -  Had histologically confirmed lung squamous cell carcinoma, or adenosquamous carcinoma;&#xD;
&#xD;
          -  Patients with pathological fracture in bone metastasis induced by non-small-cell lung&#xD;
             cancer;&#xD;
&#xD;
          -  Tumor histology or cytology confirmed EGFR mutagenesis [EGFR sensitive mutations&#xD;
             include 18 exon point mutations (G719X), 19 exon deletions, 20 exon S768I mutations&#xD;
             and 21 exon point mutations (L858R and L861Q)] and ALK gene rearrangement positivity,&#xD;
             include EGFR/ALK status cannot be determined for various reasons;&#xD;
&#xD;
          -  Imaging (CT or MRI) shows that the distance between tumor lesion and the large blood&#xD;
             vessel is ≤ 5 mm, or there is a central tumor that invades the local large blood&#xD;
             vessel; or there is a significant pulmonary cavity or necrotizing tumor; Medical&#xD;
             history and combined history：&#xD;
&#xD;
          -  Active brain metastases, cancerous meningitis, spinal cord compression, or imaging CT&#xD;
             or MRI screening for brain or pia mater disease (a patient with brain metastases who&#xD;
             have completed treatment and stable symptoms in 28 days before enrollment may be&#xD;
             enrolled, but should be confirmed by brain MRI, CT or venography evaluation as no&#xD;
             cerebral hemorrhage symptoms and metastases in midbrain, pons, cerebellum, medulla&#xD;
             oblongata, or spinal cord, brain metastases and local radiotherapy after two weeks to&#xD;
             allow group);&#xD;
&#xD;
          -  The patient is participating in other clinical studies or completing the previous&#xD;
             clinical study in less than 4 weeks;&#xD;
&#xD;
          -  Had malignant tumors except NSCLC within 5 years before enrollment(except for patients&#xD;
             with carcinoma in situ of the cervix , basal cell or squamous cell skin cancer who&#xD;
             have undergone a curative treatment, local prostate cancer after radical resection,&#xD;
             ductal carcinoma in situ or papillary thyroid cancer after radical resection);&#xD;
&#xD;
          -  Abnormal blood coagulation (INR &gt; 1.5 or prothrombin time (PT) &gt; ULN + 4 seconds or&#xD;
             APTT &gt; 1.5 ULN), with bleeding tendency or undergoing thrombolytic or anticoagulant&#xD;
             therapy; Note: Under the condition of prothrombin time international normalized ratio&#xD;
             (INR) ≤ 1.5, low-dose heparin (adult daily dose of 0.6 million to 12,000 U) or&#xD;
             low-dose aspirin (daily dosage ≤ 100 mg) is allowed for preventive purposes;&#xD;
&#xD;
          -  Renal insufficiency: urine routine indicates urinary protein ≥ ++, or confirmed&#xD;
             24-hour urine protein ≥ 1.0g;&#xD;
&#xD;
          -  The effects of surgery or trauma have been eliminated for less than 14 days before&#xD;
             enrollment in subjects who have undergone major surgery or have severe trauma;&#xD;
&#xD;
          -  Severe acute or chronic infections requiring systemic treatment; Suffering from severe&#xD;
             cardiovascular disease: myocardial ischemia or myocardial infarction above grade II,&#xD;
             poorly controlled arrhythmias (including men with QTc interval ≥ 450 ms, women ≥ 470&#xD;
             ms); according to NYHA criteria, grades III to IV Insufficient function, or cardiac&#xD;
             color Doppler ultrasound examination indicates left ventricular ejection fraction&#xD;
             (LVEF) &lt;50%;&#xD;
&#xD;
          -  There is currently a peripheral neuropathy of ≥CTCAE 2 degrees, except for trauma;&#xD;
&#xD;
          -  Respiratory syndrome (≥CTC AE grade 2 dyspnea), serous effusion (including pleural&#xD;
             effusion, ascites, pericardial effusion) requiring surgical treatment; Long-term&#xD;
             unhealed wounds or fractures;&#xD;
&#xD;
          -  Decompensated diabetes or other ailments treated with high doses of glucocorticoids;&#xD;
&#xD;
          -  Factors that have a significant impact on oral drug absorption, such as inability to&#xD;
             swallow, chronic diarrhea, and intestinal obstruction;&#xD;
&#xD;
          -  Clinically significant hemoptysis (daily hemoptysis greater than 50ml) within 3 months&#xD;
             prior to enrollment; or significant clinically significant bleeding symptoms or&#xD;
             defined bleeding tendency, such as gastrointestinal bleeding, hemorrhagic gastric&#xD;
             ulcer, baseline fecal occult blood ++ and above, or suffering from vasculitis;&#xD;
&#xD;
          -  Events of venous/venous thrombosis occurring within the first 12 months prior to&#xD;
             enrollment, such as cerebrovascular accidents (including transient ischemic attacks,&#xD;
             cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary&#xD;
             embolism;&#xD;
&#xD;
          -  Physical examination and laboratory findings:&#xD;
&#xD;
               1. A known history of HIV testing positive or acquired immunodeficiency syndrome&#xD;
                  (AIDS);&#xD;
&#xD;
               2. Untreated active hepatitis (hepatitis b: HBsAg positive and HBV DNA more than 1 x&#xD;
                  103 copy /ml; Hepatitis c: HCV RNA is positive and liver function is abnormal);&#xD;
                  Combined with hepatitis b and hepatitis c infection;&#xD;
&#xD;
               3. Serious diseases that endanger patients' safety or affect patients' completion of&#xD;
                  research,according to the researchers' judgment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Xianglin Yuan, MD.</last_name>
    <role>Study Chair</role>
    <affiliation>Tongji Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Xianglin Yuan, MD.</last_name>
    <phone>0086-13667241722</phone>
    <email>xlyuan@tjh.tjmu.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology,</name>
      <address>
        <city>Wuhan</city>
        <state>Hubei</state>
        <zip>430000</zip>
        <country>China</country>
      </address>
    </facility>
    <contact>
      <last_name>Xianglin Yuan, MD.</last_name>
      <phone>0086-13667241722</phone>
      <email>xlyuan@tjh.tjmu.cn</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 8, 2019</study_first_submitted>
  <study_first_submitted_qc>January 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 10, 2019</study_first_posted>
  <last_update_submitted>January 8, 2019</last_update_submitted>
  <last_update_submitted_qc>January 8, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 10, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Anlotinib</keyword>
  <keyword>Docetaxel</keyword>
  <keyword>Carboplatin</keyword>
  <keyword>NSCLC</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Docetaxel</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/NCT03799601
org study id: TJCC-LC-20190108
nct id: NCT03799601
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
Anlotinib which has shown an affirmatory efficacy in ALTER0303 controlled trial as a 3rd-line
      treatment on advanced NSCLC is a tyrosine kinase inhibitor with a favorable safety profile in
      phase I trial which mainly targets VEGFR1/2/3, FGFR, PDGFR and c-kit. The purpose of this
      trail is to establish whether advanced non-squamous NSCLC patients could benefit from the
      combination treatment of docetaxel, carboplatin and anlotinib as the first-line and
      maintenance treatment.
First-line patients (or postoperative recurrence) with locally advanced or metastatic NSCLC
      were enrolled in this trail. The patients (clinical stage ⅢB/Ⅳ, with no sensitizing mutation
      of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma
      kinase gene) were confirmed by histological or cytological diagnosis. The primary endpoint is
      PFS; secondary endpoint includes OS, DCR and ORR. The study was single-arm, conducted at 8
      centers in China mainland. The primary end point was PFS (time from enrollment to first
      RECIST1.1-defined PD or death). 45 patients were planned for enrollment. This estimate was
      based on 80% power, with a two-sided 5% significance level. We analyzed PFS and OS using
      Kaplan-Meier methodology. The research protocol was approved by the relevant ethics
      committees, and the study was conducted according to the Declaration of Helsinki and Good
      Clinical Practice guidelines. Patients gave written informed consent to participate in the
      trial.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: progression-free survival
time frame: Estimated about 24 months.
description: Clinical response of treatment according to RESIST v1.1 criteria (PFS, progression-free survival)
measure: Overall Survival
time frame: Estimated about 24 months.
description: Clinical response of treatment according to RESIST v1.1 criteria (OS, overall survival)
measure: Disease Control Rate
time frame: Estimated about 24 months.
description: Clinical response of treatment according to RESIST v1.1 criteria (DCR, disease control rate)
measure: Overall Response Rate
time frame: Estimated about 24 months.
description: Clinical response of treatment according to RESIST v1.1 criteria (ORR, Overall Response Rate)
arm group label: combination of docetaxel, carboplatin and anlotinib
arm group type: Experimental
intervention type: Drug
intervention name: Anlotinib
description: Anlotinib which has shown an affirmatory efficacy in ALTER0303 controlled trial as a 3rd-line treatment on advanced NSCLC is a tyrosine kinase inhibitor with a favorable safety profile in phase I trial which mainly targets VEGFR1/2/3, FGFR, PDGFR and c-kit.
arm group label: combination of docetaxel, carboplatin and anlotinib
other name: Anlotinib Hydrochloride
intervention type: Drug
intervention name: Docetaxel
description: a chemotherapy medication used to treat a number of types of cancer.This includes breast cancer, head and neck cancer, stomach cancer, prostate cancer and non-small-cell lung cancer.It may be used by itself or along with other chemotherapy medication.It is given by slow injection into a vein.
arm group label: combination of docetaxel, carboplatin and anlotinib
intervention type: Drug
intervention name: Carboplatin
description: Carboplatin is used to treat a number of forms of cancer. This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. It may be used for some types of testicular cancer but cisplatin is generally more effective.
arm group label: combination of docetaxel, carboplatin and anlotinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Xianglin Yuan, MD.
role: Study Chair
affiliation: Tongji Hospital
last name: Xianglin Yuan, MD.
phone: 0086-13667241722
email: xlyuan@tjh.tjmu.cn
facility: 
contact: 
country: China
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Carboplatin
mesh term: Docetaxel