<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/NCT03825705</url>
  </required_header>
  <id_info>
    <org_study_id>TQB2450-Ib-05</org_study_id>
    <nct_id>NCT03825705</nct_id>
  </id_info>
  <brief_title>A Study on Safety and Efficacy of TQB2450 Injection Combined With Anlotinib Hydrochloride Capsule in Patients With Advanced Biliary Adenocarcinoma/Hepatocellular Carcinoma</brief_title>
  <official_title>Phase Ib Clinical Study on Safety and Efficacy of TQB2450 Injection Combined With Anlotinib Hydrochloride Capsule in Patients With Advanced Biliary Adenocarcinoma/Hepatocellular Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chia Tai Tianqing Pharmaceutical Group Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chia Tai Tianqing Pharmaceutical Group 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>
      A single-arm, open-label clinical trial, focus on the safety and efficacy of TQB2450&#xD;
      injection combined with Anlotinib hydrochloride capsule in patients with advanced biliary&#xD;
      adenocarcinoma/hepatocellular carcinoma&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">April 23, 2019</start_date>
  <completion_date type="Anticipated">January 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">January 1, 2021</primary_completion_date>
  <phase>Phase 1/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>Overall Response Rate(ORR)</measure>
    <time_frame>Up to 96 weeks</time_frame>
    <description>Overall Response Rate (ORR) defined as the proportion of subjects who achieves a best response of CR or PR, assessed by RECIST1.1/irRECIST</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Advanced Biliary Adenocarcinoma/Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>Anlotinib + TQB2450</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TQB2450 1200 mg IV on Day 1 of each 21-day cycle plus Anlotinib capsules given orally in fasting conditions , once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TQB2450 injection</intervention_name>
    <description>TQB2450 is a humanized monoclonal antibody targeting programmed death ligand-1 (PD-L1), which prevents PD-L1 from binding to PD-1 and B7.1 receptors on T cell surface, restores T cell activity, thus enhancing immune response and has potential to treat various types of tumors.</description>
    <arm_group_label>Anlotinib + TQB2450</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anlotinib</intervention_name>
    <description>A multi-target receptor tyrosine kinase inhibitor</description>
    <arm_group_label>Anlotinib + TQB2450</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Over 18 years old; ECOG physical condition: 0 - 1 points; expected survival time more&#xD;
             than 3 months; 2、Histologically or pathologically confirmed patients with unresectable&#xD;
             or metastatic cholangiocarcinoma, including intrahepatic cholangiocarcinoma (IHCC),&#xD;
             extrahepatic cholangiocarcinoma (EHCC) and gallbladder cancer (GBC), or advanced&#xD;
             hepatocellular carcinoma (Barcelona hepatocellular carcinoma stage C, or unsuitable&#xD;
             for stage B patients who failed to receive or receive local treatment); 3、Patients had&#xD;
             at least one measurable lesion (RECIST 1.1); 4、Previous first-line chemotherapy failed&#xD;
             in patients with adenocarcinoma of the biliary system. First-line chemotherapy failure&#xD;
             is defined as disease progression during or after the last treatment, or intolerable&#xD;
             side effects during treatment. (Note: a. The first-line treatment time is more than&#xD;
             one cycle of combined chemotherapy drugs; B. Neoadjuvant or adjuvant chemotherapy is&#xD;
             allowed in the early stage. If disease progression/recurrence occurs during&#xD;
             neoadjuvant/adjuvant therapy or within 6 months after the end of treatment,&#xD;
             neoadjuvant/adjuvant therapy is considered to be the first-line systemic chemotherapy&#xD;
             failure for progressive diseases; C. Previous first-line standardized therapy does not&#xD;
             include small molecular inhibitors of angiogenesis or monoclonal antibodies or drugs&#xD;
             related to tumor immunity; Patients with hepatocellular carcinoma have not received&#xD;
             systemic chemotherapy, molecular targeted drug therapy and immunotherapy; 5、Laboratory&#xD;
             tests should be satisfied: routine blood tests: hemoglobin (Hb) &gt; 80g/L (no blood&#xD;
             transfusion within 14 days); absolute neutrophil count (ANC) &gt; 1.5 *109/L; platelet&#xD;
             (PLT) &gt; 75 *109/L; biochemical tests: alanine aminotransferase (ALT) and glutamic&#xD;
             oxaloacetate aminotransferase (AST) = 2.5 *ULN (liver metastasis of tumors, &lt; 5 *ULN);&#xD;
             serum total bilirubin (TBIL) = 2 *ULN (Gil) Patients with Bert syndrome, &lt; 3 *ULN;&#xD;
             serum creatinine (Cr) = 1.5 *ULN and creatinine clearance rate &gt; 50 umol/L;&#xD;
             coagulation function: activated partial thromboplastin time (APTT), international&#xD;
             standardized ratio (INR), prothrombin time (PT) = 1.5 *ULN; Doppler ultrasound&#xD;
             evaluation: left ventricular ejection fraction (LVEF) &gt; 50%; Child-Pugh Liver Function&#xD;
             Rating for Patients with Liver Cancer: A-B (&lt; 8 points), (Child-Pugh Albumin Rating&#xD;
             must be less than 2 points, i.e. more than 28g/L; Bilirubin Rating 1 point, TBIL &lt;&#xD;
             2.0xULN; Ascites Rating &lt; 2 points; Hepatic Encephalopathy &lt; 1 point; Prothrombin Time&#xD;
             Rating &lt; 2 points); 6、Women should agree to use contraceptive measures (such as&#xD;
             intrauterine device [IUD], contraceptive pill or condom) within 6 months of the study&#xD;
             period and the end of the study period; serum or urine pregnancy tests are negative&#xD;
             within 7 days before the study group and must be non-breastfeeding patients; men&#xD;
             should agree to use contraceptive measures during the study period and within 6 months&#xD;
             after the end of the study period; 7、The patients voluntarily joined the study and&#xD;
             signed the informed consent with good compliance.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients who had previously received treatment with target inhibitors of vascular&#xD;
             endothelial growth factor R, including Anlotinib hydrochloride capsules, or other&#xD;
             anti-PD-1/PD-L1/CTLA-4 antibodies or other immunotherapy against PD-1/PD-L1/CTLA-4&#xD;
             were treated; 2、Severe hypersensitivity was observed after administration of other&#xD;
             monoclonal antibodies; 3、Within five years, the subjects had other malignant tumors&#xD;
             (except cured basal cell carcinoma of skin, carcinoma in situ of prostate and&#xD;
             carcinoma in situ of cervix); 4、There is any active autoimmune disease or history of&#xD;
             autoimmune disease (e.g., autoimmune hepatitis, interstitial pneumonia, enteritis,&#xD;
             vasculitis, nephritis; asthma patients who need bronchiectasis for medical&#xD;
             intervention can not be included); but the following patients are allowed to enter the&#xD;
             group: vitiligo without systemic treatment, psoriasis, alopecia, well-controlled I. In&#xD;
             type 2 diabetes mellitus, hypothyroidism with normal thyroid function is treated by&#xD;
             substitution therapy; 5、Immunosuppressive therapy with immunosuppressive agents or&#xD;
             systemic or absorbable local hormones (dosage &gt; 10mg/prednisone or other therapeutic&#xD;
             hormones) is required for the purpose of immunosuppression, and is still in use for 2&#xD;
             weeks after the first administration; 6、Those with multiple factors affecting oral&#xD;
             medication, such as inability to swallow, Post-gastrointestinal resection, chronic&#xD;
             diarrhea and intestinal obstruction, etc; 7、Uncontrollable pleural effusion,&#xD;
             pericardial effusion or ascites requiring repeated drainage; 8、Regardless of the&#xD;
             severity, patients with any physical signs or history of bleeding, patients with&#xD;
             bleeding or bleeding events greater than or equal to CTCAE 3 within four weeks prior&#xD;
             to the first administration, or patients with unhealed wounds, fractures, gastric and&#xD;
             duodenal active ulcers, ulcerative colitis, or unresected tumors have active bleeding,&#xD;
             or may be caused as determined by the researchers. Other conditions of&#xD;
             gastrointestinal bleeding and perforation;9、Brain metastases were detected by CT or&#xD;
             MRI at screening, and there was a history of organ transplantation;10、Within four&#xD;
             weeks before the start of the study, the patients received approved or in-progress&#xD;
             antineoplastic therapy, including but not limited to chemotherapy, surgery,&#xD;
             radiotherapy, biological targeted therapy, interventional therapy, immunotherapy and&#xD;
             antineoplastic traditional Chinese medicine treatment (based on indications of Chinese&#xD;
             medicine instructions, such as 2-week elution period can also be included in the&#xD;
             group), etc. (Note: Oral targeting drugs with less than 5 half-lives or oral&#xD;
             fluorouracil; Patients with pyridine drugs for less than 14 days, mitomycin C and&#xD;
             nitrosourea for less than 6 weeks, and patients whose adverse events (except hair&#xD;
             loss) caused by previous treatment did not recover to &lt; CTCAE 1 degree;11、Patients&#xD;
             with any serious and/or uncontrollable disease, including:(a) Patients with&#xD;
             unsatisfactory blood pressure control (systolic blood pressure (&gt; 150 mmHg), diastolic&#xD;
             blood pressure (&gt; 90 mmHg);(b) Thrombotic events, ischemic attacks, myocardial&#xD;
             infarction, grade 2 congestive heart failure or arrhythmias requiring treatment&#xD;
             (including QTc (&gt; 480ms) occurred within 6 months of first administration;(C) Severe&#xD;
             active or uncontrolled infections (&gt; CTC AE 2 infection), tuberculosis patients;(D)&#xD;
             Known clinical history of liver diseases, including viral hepatitis, known carriers of&#xD;
             hepatitis B virus (HBV) must exclude active HBV infection, that is, HBV DNA positive&#xD;
             (&gt; 1 *104 copies/mL or &gt; 2000 IU/mL); known hepatitis C virus infection (HCV) and HCV&#xD;
             RNA positive (&gt; 1 *103 copies/mL), or other decompensated hepatitis and chronic&#xD;
             hepatitis, which require antiviral treatment. Therapy;(E) HIV positive;(F) poor&#xD;
             control of diabetes mellitus (fasting blood sugar (&gt; CTCAE 2);(G) Urinary routine&#xD;
             indicated that urinary protein (++) and confirmed 24-hour urinary protein&#xD;
             quantification (&gt;1.0 g);12、Vaccinated with vaccines or attenuated vaccines within 4&#xD;
             weeks after first administration; 13、According to the judgement of the researchers,&#xD;
             there are other factors that may lead to the termination of the study. For example,&#xD;
             other serious diseases (including mental disorders) need to be treated together, there&#xD;
             are serious abnormal laboratory examinations, accompanied by family or social factors,&#xD;
             which will affect the safety of the subjects, or the collection of data and samples.&#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>Aiping Zhou</last_name>
    <phone>010-87788800</phone>
    <email>zhouap1825@126.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Cancer Hospital Chinese Academy of Medical Sciences</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100021</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Aiping Zhou</last_name>
      <phone>010-87788800</phone>
      <email>zhouap1825@126.com</email>
    </contact>
    <investigator>
      <last_name>Aiping Zhou</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 30, 2019</study_first_submitted>
  <study_first_submitted_qc>January 30, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 31, 2019</study_first_posted>
  <last_update_submitted>October 29, 2019</last_update_submitted>
  <last_update_submitted_qc>October 29, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 31, 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>Carcinoma</mesh_term>
    <mesh_term>Adenocarcinoma</mesh_term>
    <mesh_term>Carcinoma, Hepatocellular</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/NCT03825705
org study id: TQB2450-Ib-05
nct id: NCT03825705
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
A single-arm, open-label clinical trial, focus on the safety and efficacy of TQB2450
      injection combined with Anlotinib hydrochloride capsule in patients with advanced biliary
      adenocarcinoma/hepatocellular carcinoma
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Response Rate(ORR)
time frame: Up to 96 weeks
description: Overall Response Rate (ORR) defined as the proportion of subjects who achieves a best response of CR or PR, assessed by RECIST1.1/irRECIST
arm group label: Anlotinib + TQB2450
arm group type: Experimental
description: TQB2450 1200 mg IV on Day 1 of each 21-day cycle plus Anlotinib capsules given orally in fasting conditions , once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21)
intervention type: Drug
intervention name: TQB2450 injection
description: TQB2450 is a humanized monoclonal antibody targeting programmed death ligand-1 (PD-L1), which prevents PD-L1 from binding to PD-1 and B7.1 receptors on T cell surface, restores T cell activity, thus enhancing immune response and has potential to treat various types of tumors.
arm group label: Anlotinib + TQB2450
intervention type: Drug
intervention name: Anlotinib
description: A multi-target receptor tyrosine kinase inhibitor
arm group label: Anlotinib + TQB2450
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Aiping Zhou
phone: 010-87788800
email: zhouap1825@126.com
facility: 
status: Recruiting
contact: 
investigator: 
country: China
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Adenocarcinoma
mesh term: Carcinoma, Hepatocellular