<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/NCT03811379</url>
  </required_header>
  <id_info>
    <org_study_id>PD-1/SCCE</org_study_id>
    <nct_id>NCT03811379</nct_id>
  </id_info>
  <brief_title>Toripalimab as Monotherapy for Patients With Small Cell Carcinoma of Esophagus Who Failed Chemotherapy</brief_title>
  <official_title>Phase II Clinical Trial of Toripalimab (JS001), a Recombinant Humanized Anti-PD-1 Monoclonal PD1 Antibody, as Monotherapy for Patients With Small Cell Esophageal Carcinoma Who Failed Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sun Yat-sen University</source>
  <oversight_info>
    <has_dmc>No</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>
      To evaluate the anti-tumor activity, safety and tolerance of toripalimab as monotherapy for&#xD;
      patients with small cell esophageal cancer (SCCE), and to explore the potential biomarkers&#xD;
      for this treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      For the first time in the world, the investigators revealed the genomic characteristics of&#xD;
      SCCE and constructed a complete genomic profile of SCCE. The analysis of transcriptome data&#xD;
      showed that the number of effector T cells in SCCE immune microenvironment was significantly&#xD;
      higher than that of other cancers, and NK cells were relatively high. Macrophages in SCCE&#xD;
      mainly showed M2-like phenotype and maintained at a relatively high level, suggesting the&#xD;
      possibility of immunotherapy in SCCE treatment. Therefore, the purpose of this study is to&#xD;
      clarify the efficacy of PD-1 antibody in the treatment of patients with SCCE who failed&#xD;
      chemotherapy, so as to provide a basis for further large-scale clinical research.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 21, 2018</start_date>
  <completion_date type="Anticipated">December 30, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 30, 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>Objective Response Rates (ORR)</measure>
    <time_frame>up to two year</time_frame>
    <description>the ratio of patients who are evaluated as CR or PR</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>up to two year</time_frame>
    <description>defined as the time from the first dose of study treatment to disease progression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>up to two year</time_frame>
    <description>defined as the period from the first dose of study treatment to loss of follow-up or death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of remission (DOR)</measure>
    <time_frame>up to two year</time_frame>
    <description>Defined as the time between the first assessment of a tumor as PR or CR and the first assessment as PD or any cause of death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>up to two year</time_frame>
    <description>It is defined as the proportion of patients whose tumors shrink or remain stable for a certain period of time, including CR, PR and SD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events (AEs)</measure>
    <time_frame>up to two year</time_frame>
    <description>All treatment-related adverse events (AEs) were categorized according to the National Cancer Institute's Common Terminology Criteria for Adverse Events.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">43</enrollment>
  <condition>Small Cell Carcinoma of Esophagus</condition>
  <condition>Advanced Cancer</condition>
  <arm_group>
    <arm_group_label>Toripalimab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Toripalimab, 240mg, every 3 weeks until disease progress or intolerable toxicity</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Toripalimab</intervention_name>
    <description>Drug: Toripalimab, 240mg, every 3 weeks until disease progress or intolerable toxicity</description>
    <arm_group_label>Toripalimab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Full understanding of the study and voluntary signing of informed consent&#xD;
&#xD;
          2. Histologically and/or cytologically confirmed advanced and/or metastatic small cell&#xD;
             carcinoma of the esophagus who failed previous first-line or more lines of&#xD;
             chemotherapy or the disease recurs within six months after the adjuvant or neoadjuvant&#xD;
             therapy&#xD;
&#xD;
          3. At least one measurable lesion (according to RECIST 1.1) Note: Lesions previously&#xD;
             treated with radiotherapy should not be considered as target lesions unless there is a&#xD;
             definite progression after radiotherapy.&#xD;
&#xD;
          4. Agree to provide previously stored specimens of tumor tissue or to perform biopsy to&#xD;
             collect tumor tissue for PD-L1 IHC detection.&#xD;
&#xD;
          5. The age ranges from 18 to 75 years with no gender limitation.&#xD;
&#xD;
          6. ECOG: 0-1&#xD;
&#xD;
          7. Expected survival ≧ 3 months&#xD;
&#xD;
          8. Laboratory tests within 7 days before admission must meet the following criteria: A.&#xD;
             Neutrophils≧1.5 *109/L; B. Platelet ≧ 75 *109/L; C. Hemoglobin≧90g/L (no infusion of&#xD;
             concentrated red blood cells within 2 weeks); D. Serum creatinine≦1.5 * ULN, or&#xD;
             creatinine clearance rate &gt; 50 mL/min; E. Serum total bilirubin ≦ 1.5 *ULN (Gilbert&#xD;
             syndrome subjects allowed total bilirubin ≦ 3 *ULN); F. AST and ALT ≦ 2.5 *ULN, while&#xD;
             ALT and AST were less than 5 *ULN in subjects with liver metastasis.&#xD;
&#xD;
          9. Within 21 days before admission, women of childbearing age must confirm that the serum&#xD;
             pregnancy test is negative and agree to use effective contraceptive measures during&#xD;
             the study period and within 28 days after the last administration. Female reproductive&#xD;
             age in this program is defined as sexually mature women: 1) without hysterectomy or&#xD;
             bilateral ovariectomy, 2) natural menopause without continuous 24 months (menopause&#xD;
             after cancer treatment does not exclude fertility) (Menstruation occurs at any time&#xD;
             during the previous 24 consecutive months).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. known to be allergic to citric acid monohydrate, sodium citrate dihydrate, mannitol&#xD;
             and polysorbide (components of the test drug).&#xD;
&#xD;
          2. Within the first four weeks of admission, patients received anti-tumor cytotoxic&#xD;
             drugs, biological drugs (such as monoclonal antibodies), immunotherapy (such as&#xD;
             interleukin-2 or interferon), or other research drugs.&#xD;
&#xD;
          3. Tyrosine kinase inhibitors were administered within 2 weeks before admission.&#xD;
&#xD;
          4. Radiotherapy or radiopharmacotherapy were given within 4 weeks or 8 weeks before&#xD;
             admission, except local palliative radiotherapy for bone metastases.&#xD;
&#xD;
          5. Major surgical operations were performed or not fully recovered from previous&#xD;
             operations within the first four weeks of enrollment (the definition of major surgical&#xD;
             operations refers to the 3-and 4-level operations stipulated in the Regulations on the&#xD;
             Clinical Application of Medical Technologies, which were implemented on 1 May 2009).&#xD;
&#xD;
          6. The toxicity of previous antineoplastic therapies has not been restored to CTCAE 0-1,&#xD;
             except for the following cases:&#xD;
&#xD;
             A alopecia; B pigmentation; C Peripheral neurotoxicity has been restored to &lt; CTCAE&#xD;
             level 2. D The long-term toxicity caused by radiotherapy can not be restored by the&#xD;
             judgement of the researchers.&#xD;
&#xD;
          7. Subjects with clinical symptoms of central nervous system metastasis (e.g. brain&#xD;
             edema, requiring hormone intervention, or progression of brain metastasis) and/or&#xD;
             cancerous meningitis. Subjects who had previously received brain or meningeal&#xD;
             metastasis therapy, such as clinical stability maintained for at least two months, and&#xD;
             who had stopped systemic sex hormone therapy (prednisone or other therapeutic hormones&#xD;
             at doses greater than 10 mg/day) for more than four weeks could be included.&#xD;
&#xD;
          8. Other malignant tumors (besides skin basal cell carcinoma, breast/cervical carcinoma&#xD;
             in situ, and other malignancies that have not been treated and effectively controlled&#xD;
             in the past five years) have been or are currently co-existing with other malignant&#xD;
             tumors.&#xD;
&#xD;
          9. Subjects had any history of active autoimmune diseases or autoimmune diseases&#xD;
             (including, but not limited to, interstitial pneumonia, uveitis, enteritis, hepatitis,&#xD;
             pituitary inflammation, nephritis, hyperthyroidism, hypothyroidism); subjects with&#xD;
             vitiligo or childhood asthma had been completely alleviated; subjects without any&#xD;
             intervention after adulthood could be included in the study; Asthma, which requires&#xD;
             medical intervention with bronchodilators, cannot be included.&#xD;
&#xD;
         10. Anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody or anti-CTLA-4 antibody&#xD;
             (or any other antibody acting on T cell co-stimulation or checkpoint pathway) have&#xD;
             been used in the past.&#xD;
&#xD;
         11. Subjects with active pulmonary tuberculosis (TB) are receiving anti-tuberculosis&#xD;
             treatment or anti-tuberculosis treatment within one year before screening.&#xD;
&#xD;
         12. Complications of corticosteroids requiring long-term use of immunosuppressive drugs or&#xD;
             systemic or local use of prednisone or other therapeutic hormones with an&#xD;
             immunosuppressive dose of more than 10 mg/day.&#xD;
&#xD;
         13. Any anti-infective vaccines (such as influenza vaccine, varicella vaccine, etc.) were&#xD;
             inoculated within 4 weeks before admission.&#xD;
&#xD;
         14. Pregnant or lactating women.&#xD;
&#xD;
         15. HIV positive.&#xD;
&#xD;
         16. HBsAg positive and HBV DNA copy number positive (quantitative detection ≧ 1000&#xD;
             cps/ml).&#xD;
&#xD;
         17. Blood screening for chronic hepatitis C is positive (HCV antibody is positive).&#xD;
&#xD;
         18. Researchers believe that it may affect program compliance, or the signing of informed&#xD;
             consent (ICF), or any other disease or condition of clinical significance that is not&#xD;
             suitable for this clinical trial.&#xD;
&#xD;
         19. Heart clinical symptoms or diseases that have not been well controlled, such as:&#xD;
&#xD;
        (1) heart failure above NYHA Level 2 (2) unstable angina pectoris (3) myocardial infarction&#xD;
        within 1 year (4) clinically significant supraventricular or ventricular arrhythmias need&#xD;
        treatment or intervention;&#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>Rui-hua Xu, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sun Yat-sen University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Feng Wang, MD, PhD</last_name>
    <phone>+8602087342635</phone>
    <email>lvzd@sysucc.org.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>Cancer center of Sun Yat-sen University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rui-Hua Xu, MD, PhD</last_name>
      <phone>+862087342635</phone>
      <email>lvzd@sysucc.org.cn</email>
    </contact>
    <investigator>
      <last_name>Rui-hua Xu, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Feng Wang, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 17, 2019</study_first_submitted>
  <study_first_submitted_qc>January 17, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 22, 2019</study_first_posted>
  <last_update_submitted>January 21, 2019</last_update_submitted>
  <last_update_submitted_qc>January 21, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 23, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>Ruihua Xu</investigator_full_name>
    <investigator_title>President and professor</investigator_title>
  </responsible_party>
  <keyword>Immunotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Small Cell</mesh_term>
    <mesh_term>Small Cell Lung Carcinoma</mesh_term>
    <mesh_term>Esophageal Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03811379
org study id: PD-1/SCCE
nct id: NCT03811379
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
To evaluate the anti-tumor activity, safety and tolerance of toripalimab as monotherapy for
      patients with small cell esophageal cancer (SCCE), and to explore the potential biomarkers
      for this treatment.
For the first time in the world, the investigators revealed the genomic characteristics of
      SCCE and constructed a complete genomic profile of SCCE. The analysis of transcriptome data
      showed that the number of effector T cells in SCCE immune microenvironment was significantly
      higher than that of other cancers, and NK cells were relatively high. Macrophages in SCCE
      mainly showed M2-like phenotype and maintained at a relatively high level, suggesting the
      possibility of immunotherapy in SCCE treatment. Therefore, the purpose of this study is to
      clarify the efficacy of PD-1 antibody in the treatment of patients with SCCE who failed
      chemotherapy, so as to provide a basis for further large-scale clinical research.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rates (ORR)
time frame: up to two year
description: the ratio of patients who are evaluated as CR or PR
measure: Progression free survival (PFS)
time frame: up to two year
description: defined as the time from the first dose of study treatment to disease progression
measure: Overall Survival (OS)
time frame: up to two year
description: defined as the period from the first dose of study treatment to loss of follow-up or death
measure: Duration of remission (DOR)
time frame: up to two year
description: Defined as the time between the first assessment of a tumor as PR or CR and the first assessment as PD or any cause of death
measure: Disease Control Rate (DCR)
time frame: up to two year
description: It is defined as the proportion of patients whose tumors shrink or remain stable for a certain period of time, including CR, PR and SD.
measure: Adverse Events (AEs)
time frame: up to two year
description: All treatment-related adverse events (AEs) were categorized according to the National Cancer Institute's Common Terminology Criteria for Adverse Events.
arm group label: Toripalimab
arm group type: Experimental
description: Toripalimab, 240mg, every 3 weeks until disease progress or intolerable toxicity
intervention type: Drug
intervention name: Toripalimab
description: Drug: Toripalimab, 240mg, every 3 weeks until disease progress or intolerable toxicity
arm group label: Toripalimab
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Rui-hua Xu, MD, PhD
role: Principal Investigator
affiliation: Sun Yat-sen University
last name: Feng Wang, MD, PhD
phone: +8602087342635
email: lvzd@sysucc.org.cn
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Ruihua Xu
investigator title: President and professor
mesh term: Carcinoma
mesh term: Carcinoma, Small Cell
mesh term: Small Cell Lung Carcinoma
mesh term: Esophageal Neoplasms
sharing ipd: Undecided