<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/NCT04503967</url>
  </required_header>
  <id_info>
    <org_study_id>OASIS</org_study_id>
    <nct_id>NCT04503967</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Anlotinib Hydrochloride Combined With Nivolumab in the Treatment of Gastric and Esophageal Cancer</brief_title>
  <acronym>OASIS</acronym>
  <official_title>A Phase II Study to Evaluate the Efficacy and Safety of Anlotinib Hydrochloride Combined With Nivolumab in the Treatment of Advanced Gastric Adenocarcinoma and Esophageal Squamous Cell Carcinoma as Second-line or Salvage Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Zhongshan Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shanghai Zhongshan Hospital</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>
      Patients with unresectable or metastatic gastric or esophageal cancer, with first-line&#xD;
      treatment applied are to be recruited in the study. In the current study, the efficacy and&#xD;
      safety of anlotinib hydrochloride combined with nivolumab as second-line or salvage&#xD;
      chemotherapy will be evaluated in Chinese patients with advanced gastric adenocarcinoma and&#xD;
      esophageal squamous cell carcinoma. 48 patients could provide adequate precision rather than&#xD;
      controlling type I&amp;II error.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">August 1, 2020</start_date>
  <completion_date type="Anticipated">August 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">February 1, 2021</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>Objective response rate</measure>
    <time_frame>up to 2 years</time_frame>
    <description>The ORR in patients with unresectable or metastatic GC or ESCC patients treated with anlotinib hydrochloride in combination with nivolumab as a second-line or later treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>up to 2 years</time_frame>
    <description>The PFS was calculated from the initiation of chemotherapy to the date of disease progression or death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Overall survival was measured from the initiation of chemotherapy to the date of the last follow-up or death.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">48</enrollment>
  <condition>Gastric Adenocarcinoma</condition>
  <condition>Esophageal Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Anlotinib Hydrochloride With Nivolumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Anlotinib Hydrochloride Combined With Nivolumab in the second line treatment of Gastric and Esophageal Cancer patients</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anlotinib Hydrochloride With Nivolumab</intervention_name>
    <description>Anlotinib Hydrochloride Combined With Nivolumab in the second line Treatment of Gastric and Esophageal Cancer patients</description>
    <arm_group_label>Anlotinib Hydrochloride With Nivolumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. The patient volunteers to participate in the study, signs a consent form, has good&#xD;
             compliance, and obeys the follow-up, and is willing and able to follow the protocol&#xD;
             during the study.&#xD;
&#xD;
          2. Male or female, aged ≥18 years and ≤75 years.&#xD;
&#xD;
          3. The ECOG PS score is 0 or 1.&#xD;
&#xD;
          4. Histological and/or cytological confirmation of patients with unresectable or&#xD;
             metastatic gastric adenocarcinoma or esophageal squamous cell carcinoma.&#xD;
&#xD;
          5. Patients have failed previous first-line standard treatments, have measurable target&#xD;
             lesions, and have not received local treatments such as radiotherapy for target&#xD;
             lesions (Note: lesions that have previously received radiation therapy cannot be&#xD;
             considered target lesions, except that after radiation therapy, clear progress has&#xD;
             occurred).&#xD;
&#xD;
          6. At least 4 weeks after previous major surgical and / or radiation therapy (at least 2&#xD;
             weeks after palliative radiotherapy).&#xD;
&#xD;
          7. The use of 0-1 antihypertensive drug can effectively control blood pressure, which is&#xD;
             defined as random pre-systolic blood pressure ≤140mmHg, diastolic blood pressure&#xD;
             ≤90mmHg, and no antihypertensive drug has been changed within one week before&#xD;
             randomization.&#xD;
&#xD;
          8. Appropriate bone marrow reserve, as shown in the blood count of the subject within 7&#xD;
             days before enrollment: hemoglobin ≥90g / L; ANC ≥1.5 × 109 / L; platelet ≥90 × 109 /&#xD;
             L (patients have not received blood transfusion or growth factor support within 2&#xD;
             weeks prior blood collection).&#xD;
&#xD;
          9. Appropriate liver function is shown to meet all of the following requirements:&#xD;
&#xD;
               1. Serum total bilirubin ≤ 1.5 x ULN (Gilbert syndrome patients can be included if&#xD;
                  the total bilirubin is &lt;3 x ULN, and those with biliary obstruction allow biliary&#xD;
                  drainage);&#xD;
&#xD;
               2. serum albumin ≥30g / L;&#xD;
&#xD;
               3. AST, ALT ≤ 3 x ULN (If liver metastases exist, AST and ALT allow ≤ 5 x ULN).&#xD;
&#xD;
         10. Appropriate renal function demonstrated by all of the following requirements:&#xD;
&#xD;
               1. Serum creatinine ≤ 1.5 x ULN and creatinine clearance ≥ 50ml/min (using&#xD;
                  Cockcroft-Gault formula);&#xD;
&#xD;
               2. Proteinuria &lt;++; if proteinuria is ≥++, 24-hour urine protein must be &lt;2g.&#xD;
&#xD;
         11. INR or prothrombin time (PT) ≤ 1.5 x ULN, APTT ≤ 1.5 x ULN; no history of&#xD;
             anticoagulant treatment; investigator judges no high coagulation risk.&#xD;
&#xD;
         12. All acute toxic effects of previous anti-cancer treatment or surgery were all relieved&#xD;
             by NCI-CTCAE version 5.0 ≤ 1 (except for hair loss or other toxic effects that the&#xD;
             investigator judges to have no risk to the patient's safety).&#xD;
&#xD;
         13. Fertile women must have a negative urine or serum pregnancy test within 7 days before&#xD;
             enrollment, and must agree to use effective contraception during the study period and&#xD;
             within 6 months after the end of the study period; non-sterile men must agree to use&#xD;
             efficient contraception during the study period and within 6 months after the study&#xD;
             was completed. Patient agrees to avoid sperm donation during the same time period.&#xD;
&#xD;
         14. Have the ability to act autonomously, have the ability to swallow pills, and have no&#xD;
             gastrointestinal diseases that affect oral drug absorption.&#xD;
&#xD;
         15. Agree to provide hematology and histology samples.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Have undifferentiated or other histological types of gastric or esophageal cancer;&#xD;
             evidence of tumor invasion of major blood vessels (including completely adjacent,&#xD;
             surrounding, or extending into the main vessel lumen, such as the pulmonary artery or&#xD;
             superior vena cava) , and the researcher judges that it is not suitable for&#xD;
             enrollment.&#xD;
&#xD;
          2. Patients with active autoimmune disease or a history of autoimmune disease but who may&#xD;
             relapse.&#xD;
&#xD;
             Note: Patients with the following diseases are not excluded and can be entered for&#xD;
             further screening:&#xD;
&#xD;
               1. Controlled Type 1 Diabetes&#xD;
&#xD;
               2. Hypothyroidism (if only controlled by hormone replacement therapy)&#xD;
&#xD;
               3. Controlled celiac disease&#xD;
&#xD;
               4. Skin diseases that do not require systemic treatment (e.g. vitiligo, psoriasis,&#xD;
                  hair loss)&#xD;
&#xD;
               5. Any other disease that is not expected to recur without external triggers&#xD;
&#xD;
          3. Any active malignant tumor within 2 years, except for the specific cancer being&#xD;
             studied in this trial and cured local recurrent cancer (such as resected basal cell or&#xD;
             squamous cell skin cancer, superficial bladder cancer, cervical or breast carcinoma in&#xD;
             situ).&#xD;
&#xD;
          4. There is uncontrollable pleural effusion, pericardial effusion, or ascites that need&#xD;
             to be drained frequently within 7 days before enrollment (allow effusion cytology to&#xD;
             confirm).&#xD;
&#xD;
          5. Patients with gastrointestinal bleeding within two weeks before enrollment, or those&#xD;
             at high risk of bleeding as judged by the investigator (Note: fecal occult blood (+)&#xD;
             is not an exclusion criterion).&#xD;
&#xD;
          6. Gastrointestinal perforation and / or fistula occurred within 6 months before&#xD;
             enrollment.&#xD;
&#xD;
          7. There are many factors that affect oral drug absorption (such as inability to swallow,&#xD;
             nausea and vomiting, upper gastrointestinal obstruction, abnormal physiological&#xD;
             function, malabsorption syndrome, etc.), which may affect anlotinib hydrochloride&#xD;
             absorbers.&#xD;
&#xD;
          8. Weight loss ≥ 20% within 2 months before enrollment.&#xD;
&#xD;
          9. History of the following diseases: interstitial lung disease, non-infectious pneumonia&#xD;
             or uncontrollable systemic diseases including diabetes, hypertension, pulmonary&#xD;
             fibrosis, acute lung disease, etc.&#xD;
&#xD;
         10. Severe chronic or active infections, including tuberculosis, that require systemic&#xD;
             antibacterial, antifungal or antiviral treatment.&#xD;
&#xD;
         11. Known history of HIV infection.&#xD;
&#xD;
         12. Patients with untreated chronic hepatitis B or chronic HBV carriers with hepatitis B&#xD;
             virus (HBV) DNA exceeding ULN, or hepatitis C virus (HCV) RNA positive should be&#xD;
             excluded. Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable&#xD;
             patients with hepatitis B (HBV DNA &lt;ULN), and patients with cured hepatitis C can be&#xD;
             selected.&#xD;
&#xD;
         13. Have any of the following cardiovascular risk factors:&#xD;
&#xD;
               1. Cardiogenic chest pain occurs within ≤ 28 days prior to enrollment, and is&#xD;
                  defined as moderate pain that limits the daily use of appliance sexual activity.&#xD;
&#xD;
               2. Symptomatic pulmonary embolism occurred within ≤ 28 days before enrollment.&#xD;
&#xD;
               3. Acute myocardial infarction occurred within ≤ 6 months before enrollment.&#xD;
&#xD;
               4. Have any history of heart failure that has reached New York Heart Association&#xD;
                  Grade III / IV within ≤ 6 months before enrollment, or left ventricular ejection&#xD;
                  fraction &lt;50%.&#xD;
&#xD;
               5. Ventricular arrhythmia of grade ≥ 2 occurred within ≤ 6 months before enrollment.&#xD;
&#xD;
               6. Cerebrovascular accident (CVA) occurred within ≤ 6 months before enrollment&#xD;
&#xD;
               7. Those with high blood pressure who cannot be controlled well with&#xD;
                  antihypertensive medications. The symptoms are: systolic blood pressure&gt; 140&#xD;
                  mmHg, diastolic blood pressure&gt; 90 mmHg (within 3 months).&#xD;
&#xD;
               8. Significant cardiac conduction abnormalities, including a history of QTc interval&#xD;
                  prolongation syndrome (QTc interval prolongation&gt; 450 ms) and/or a history of&#xD;
                  pacemaker implantation.&#xD;
&#xD;
         14. Patients receiving oral or parenteral anticoagulant or thrombolytic treatment for&#xD;
             therapeutic purposes during screening and/or during the study should be excluded.&#xD;
&#xD;
         15. The patient has brain metastases or meningeal metastases.&#xD;
&#xD;
         16. People who are allergic to any research medication.&#xD;
&#xD;
         17. Have had an allogeneic stem cell transplant or organ transplant.&#xD;
&#xD;
         18. Corticosteroids (prednisone or similar drugs at doses greater than 10 mg/day are&#xD;
             required for ≤ 14 days before enrollment) Equal dose) or other immunosuppressive&#xD;
             agents for systemic treatment.&#xD;
&#xD;
             Note: Patients who are currently or previously using any of the following steroid&#xD;
             regimens can be selected:&#xD;
&#xD;
               1. Adrenaline replacement steroids (prednisone ≤10mg / d or equivalent dose of&#xD;
                  similar drugs)&#xD;
&#xD;
               2. Local, ophthalmic, intra-articular, intranasal, and inhaled corticosteroids with&#xD;
                  minimal systemic absorption.&#xD;
&#xD;
               3. Short-term (≤ 7 days) use of corticosteroids for prophylaxis (for example, to&#xD;
                  prevent contrast agent hypersensitivity or antiemetic for specific chemotherapy)&#xD;
                  or for the treatment of non-autoimmune conditions (such as delayed&#xD;
                  hypersensitivity caused by contact allergens).&#xD;
&#xD;
         19. Live vaccinations were given within 4 weeks before randomization (Note: seasonal&#xD;
             influenza vaccines are usually inactivated vaccines and are allowed. Vaccines used in&#xD;
             the nasal cavity are live vaccines and are not allowed).&#xD;
&#xD;
         20. Have received immunotherapy (such as interleukin, interferon, thymosin, etc.) or any&#xD;
             experimental treatment within 28 days or 5 half-lives (whichever is shorter, but at&#xD;
             least 14 days) before enrollment.&#xD;
&#xD;
         21. Having received anti-PD-1, anti-PD-L1, anti-PD-L2, or any other specific antibody or&#xD;
             drug therapy that targets T-cell co-stimulation or checkpoint pathways.&#xD;
&#xD;
         22. For those with a history of uncontrolled epilepsy, central nervous system disease, or&#xD;
             mental disorder, it is up to the investigator to determine whether their clinical&#xD;
             severity prevents the signing of informed consent or affects the patient's compliance&#xD;
             with oral medication.&#xD;
&#xD;
         23. There are potential medical conditions or alcohol/drug abuse or dependence that the&#xD;
             investigator believes are not conducive to the administration of the study drug or&#xD;
             affect the interpretation of drug toxicity or adverse events.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>15 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>August 5, 2020</study_first_submitted>
  <study_first_submitted_qc>August 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2020</study_first_posted>
  <last_update_submitted>August 5, 2020</last_update_submitted>
  <last_update_submitted_qc>August 5, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 7, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shanghai Zhongshan Hospital</investigator_affiliation>
    <investigator_full_name>Tianshu Liu</investigator_full_name>
    <investigator_title>Doctor</investigator_title>
  </responsible_party>
  <keyword>Gastric Cancer</keyword>
  <keyword>esophageal cancer</keyword>
  <keyword>Anlotinib Hydrochloride</keyword>
  <keyword>Nivolumab</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Adenocarcinoma</mesh_term>
    <mesh_term>Esophageal Squamous Cell Carcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nivolumab</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/NCT04503967
org study id: OASIS
nct id: NCT04503967
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Patients with unresectable or metastatic gastric or esophageal cancer, with first-line
      treatment applied are to be recruited in the study. In the current study, the efficacy and
      safety of anlotinib hydrochloride combined with nivolumab as second-line or salvage
      chemotherapy will be evaluated in Chinese patients with advanced gastric adenocarcinoma and
      esophageal squamous cell carcinoma. 48 patients could provide adequate precision rather than
      controlling type I&II error.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective response rate
time frame: up to 2 years
description: The ORR in patients with unresectable or metastatic GC or ESCC patients treated with anlotinib hydrochloride in combination with nivolumab as a second-line or later treatment.
measure: Progression-free survival
time frame: up to 2 years
description: The PFS was calculated from the initiation of chemotherapy to the date of disease progression or death.
measure: Overall survival
time frame: up to 2 years
description: Overall survival was measured from the initiation of chemotherapy to the date of the last follow-up or death.
arm group label: Anlotinib Hydrochloride With Nivolumab
arm group type: Experimental
description: Anlotinib Hydrochloride Combined With Nivolumab in the second line treatment of Gastric and Esophageal Cancer patients
intervention type: Drug
intervention name: Anlotinib Hydrochloride With Nivolumab
description: Anlotinib Hydrochloride Combined With Nivolumab in the second line Treatment of Gastric and Esophageal Cancer patients
arm group label: Anlotinib Hydrochloride With Nivolumab
criteria: 
gender: All
minimum age: 15 Years
maximum age: 75 Years
healthy volunteers: No
responsible party type: Principal Investigator
investigator affiliation: Shanghai Zhongshan Hospital
investigator full name: Tianshu Liu
investigator title: Doctor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Adenocarcinoma
mesh term: Esophageal Squamous Cell Carcinoma
mesh term: Nivolumab