<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/NCT04501029</url>
  </required_header>
  <id_info>
    <org_study_id>ST1481-LEES-2020-03</org_study_id>
    <nct_id>NCT04501029</nct_id>
  </id_info>
  <brief_title>A Study of Gimatecan (ST1481) in Small Cell Lung Cancer</brief_title>
  <official_title>A Phase Ib/II Study of Gimatecan (ST1481) for Small Cell Lung Cancer Patients Who Failed Standard Platinum-containing Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lee's Pharmaceutical Limited</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Lee's Pharmaceutical Limited</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>
      This phase Ib/II clinical trial studies the safety and effect of Gimatecan in small cell lung&#xD;
      cancer patients who failed the first-line standard platinum-containing chemotherapy. The&#xD;
      chemotherapy will be given every four weeks.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">October 1, 2020</start_date>
  <completion_date type="Anticipated">October 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">October 1, 2022</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>Dose limited toxicity (DLT)</measure>
    <time_frame>up to 28 days.</time_frame>
    <description>Phase Ib: Number of patients experienced any dose limited toxicity over the DLT period.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Recommended phase II dose (RP2D)</measure>
    <time_frame>up to 12 months.</time_frame>
    <description>Phase Ib: Determination of recommended phase II dose of escalating dose of gimatecan for the phase II part of the study.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>To evaluate objective response rate every 8 weeks after the initiation of chemotherapy, up to 24 months.</time_frame>
    <description>Percentage of patients with objective response assessed by best overall response (BOR) of either complete response(CR) or partial remission(PR) will be reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>From date of randomization until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 24 months.</time_frame>
    <description>The 2-year progression free survival of the whole group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate (DCR)</measure>
    <time_frame>To evaluate disease control rate every 8 weeks after the initiation of chemotherapy, up to 24 months.</time_frame>
    <description>Percentage of patients with disease control as assessed by best overall response (BOR) of either complete response(CR), partial remission(PR) or stable disease (SD) will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DoR)</measure>
    <time_frame>First documented CR or PR, whichever is first recorded until the first assessment of PD, assessed up to 24 months.</time_frame>
    <description>The DoR applies only to patients whose BOR is either CR or PR. The duration is measured from the first documented response (CR or PR, whichever is first recorded) until the first assessment of Progressive Disease (PD).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>From date of randomization until the date of death from any cause or the date of last follow-up whichever came first, assessed up to 24 months.</time_frame>
    <description>The 2-year overall survival of the whole group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival rate (SR)</measure>
    <time_frame>up to 24 months.</time_frame>
    <description>Survival probability of patients calculated according to Kaplan-Meier curve at either 1 or 2 year.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment related adverse events rate</measure>
    <time_frame>From the enrollment to 30 days later of the last chemotherapy.</time_frame>
    <description>The incidence rate of treatment related adverse events of the whole group assessed by CTCAE v5.0.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">70</enrollment>
  <condition>Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Gimatecan group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In Phase Ib study, patients will receive gimatecan at different dose level (0.4mg/m2, 0.6mg/m2,0.8mg/m2, oral, every 4 weeks) until progressive disease (PD).In Phase II study, patients will receive gimatecan at recommended phase II dose level.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gimatecan</intervention_name>
    <description>Patients will receive gimatecan orally at the recommended dose level on day 1-5 every 4 weeks.</description>
    <arm_group_label>Gimatecan group</arm_group_label>
    <other_name>ST1481</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          1. Aged 18 to 75 years old of either gender;&#xD;
&#xD;
          2. A histopathological or cytological diagnosis of small cell lung cancer(SCLC);&#xD;
&#xD;
          3. Recurrence or progression disease after firstline platinum-containing chemotherapy and&#xD;
             patients intolerant or unwilling to receive standard treatment;&#xD;
&#xD;
          4. Measurable cancer lesion according to Response Evaluation Criteria in Solid Tumors&#xD;
             (RECIST) v1.1;&#xD;
&#xD;
          5. Eastern Cooperative Oncology Group(ECOG) performance status score 0-1;&#xD;
&#xD;
          6. Estimated life expectancy &gt;4 months;&#xD;
&#xD;
          7. Taking drugs orally;&#xD;
&#xD;
          8. The function of important organs meets the following requirements:&#xD;
&#xD;
               1. white blood cell count (WBC) ≥ 4.0×109/L, absolute neutrophil count (ANC) ≥&#xD;
                  1.5×109/L, platelets ≥ 100×109/L, hemoglobin ≥ 90g/L;&#xD;
&#xD;
               2. ALT, AST and AKP ≤ 2.5×ULN; liver metastasis: ALT、AST≤ 5.0×ULN, ALP ≤ 6.0×ULN;&#xD;
                  bone metastases ALT、AST≤ 2.5×ULN, ALP ≤ 5.0×ULN;&#xD;
&#xD;
               3. serum albumin ≥ 30g/L;&#xD;
&#xD;
               4. total bilirubin ≤ 1.5×ULN;&#xD;
&#xD;
               5. serum creatinine ≤ 1.5×ULN, creatinine clearance rate ≥60 mL/min;&#xD;
&#xD;
               6. INR ≤ 1.5, PT≤ 1.5×ULN;&#xD;
&#xD;
        10. Serum HCG negative in premenopausal women, female patients of childbearing potential&#xD;
        and male patients with female partners of childbearing potential must be willing to avoid&#xD;
        pregnancy; 11. Ability to understand the study and sign informed consent.&#xD;
&#xD;
        Key exclusion Criteria:&#xD;
&#xD;
          1. Patients who have been treated previously for SCLC with two system chemotherapy&#xD;
             (except for targeted therapy, immunotherapy and antiangiogenic therapy);&#xD;
&#xD;
          2. Patients who have been treated previously with topotecan, Irinotecan or other&#xD;
             topoisomerase I inhibitors;&#xD;
&#xD;
          3. Known or suspected allergy or hypersensitivity to the investigational drug gimatecan&#xD;
             ingredients or their analogues;&#xD;
&#xD;
          4. Other anticancer therapy including any investigational agent within 28 days prior to&#xD;
             the first dose of the investigational drug gimatecan;&#xD;
&#xD;
          5. Patients who have been treated previously with intravenous or oral drugs that affect&#xD;
             CYP isoenzymes within 7 days prior to the first dose of the investigational drug&#xD;
             gimatecan;&#xD;
&#xD;
          6. Brain metastasis or meningeal metastasis (except for asymptomatic patients with lesion&#xD;
             stable more than 28 days);&#xD;
&#xD;
          7. Major surgical intervention or trauma within 28 days prior to the first dose of&#xD;
             investigational drug administration;&#xD;
&#xD;
          8. A history of gastrointestinal disease which affects drug absorption;&#xD;
&#xD;
          9. A history of allogeneic stem cell transplantation and organ transplantation;&#xD;
&#xD;
         10. A history of interstitial lung disease or non-infectious pneumonia;&#xD;
&#xD;
         11. Patients who cannot tolerate chemotherapy due to severe cardiac, lung, liver or kidney&#xD;
             dysfunction, or hematopoietic disease or cachexia;&#xD;
&#xD;
         12. A history of immunodeficiency (including a positive HIV test result), or other&#xD;
             acquired or congenital immunodeficiency diseases;&#xD;
&#xD;
         13. Presence of active hepatitis B (HBV DNA ≥ 200 IU/mL or 103 copies/mL), hepatitis C&#xD;
             (positive for hepatitis C antibody, and HCV-RNA levels higher than the lower limit of&#xD;
             the assay);&#xD;
&#xD;
         14. A history of active pulmonary tuberculosis infection within 1 year or a history of&#xD;
             active pulmonary tuberculosis infection more than 1 year ago but without formal&#xD;
             anti-tuberculosis treatment;&#xD;
&#xD;
         15. A history of malignancies other than esophageal cancer before enrollment, excluding&#xD;
             non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer;&#xD;
&#xD;
         16. Pregnant or lactating women.&#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>LIU XIAOQING, MD</last_name>
    <role>Study Director</role>
    <affiliation>The Fifth Medical Center of the Chinese PLA General Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>LIU XIAOQING, MD</last_name>
    <phone>86-010-66947797</phone>
    <email>liuxiaoqing@csco.org.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>The Fifth Medical Center of General Hospital of the Chinese People's Liberation Army</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100071</zip>
        <country>China</country>
      </address>
    </facility>
    <contact>
      <last_name>LIU XIAOQING, MD</last_name>
      <phone>86-010-66947797</phone>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <results_reference>
    <citation>Hurwitz JL, McCoy F, Scullin P, Fennell DA. New advances in the second-line treatment of small cell lung cancer. Oncologist. 2009 Oct;14(10):986-94. doi: 10.1634/theoncologist.2009-0026. Epub 2009 Oct 9.</citation>
    <PMID>19819917</PMID>
  </results_reference>
  <results_reference>
    <citation>Owonikoko TK, Behera M, Chen Z, Bhimani C, Curran WJ, Khuri FR, Ramalingam SS. A systematic analysis of efficacy of second-line chemotherapy in sensitive and refractory small-cell lung cancer. J Thorac Oncol. 2012 May;7(5):866-72. doi: 10.1097/JTO.0b013e31824c7f4b.</citation>
    <PMID>22722788</PMID>
  </results_reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 30, 2020</study_first_submitted>
  <study_first_submitted_qc>August 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <last_update_submitted>August 2, 2020</last_update_submitted>
  <last_update_submitted_qc>August 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 6, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>small cell lung cancer</keyword>
  <keyword>chemotherapy</keyword>
  <keyword>gimatecan</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Small Cell Lung Carcinoma</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/NCT04501029
org study id: ST1481-LEES-2020-03
nct id: NCT04501029
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This phase Ib/II clinical trial studies the safety and effect of Gimatecan in small cell lung
      cancer patients who failed the first-line standard platinum-containing chemotherapy. The
      chemotherapy will be given every four weeks.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose limited toxicity (DLT)
time frame: up to 28 days.
description: Phase Ib: Number of patients experienced any dose limited toxicity over the DLT period.
measure: Recommended phase II dose (RP2D)
time frame: up to 12 months.
description: Phase Ib: Determination of recommended phase II dose of escalating dose of gimatecan for the phase II part of the study.
measure: Objective response rate (ORR)
time frame: To evaluate objective response rate every 8 weeks after the initiation of chemotherapy, up to 24 months.
description: Percentage of patients with objective response assessed by best overall response (BOR) of either complete response(CR) or partial remission(PR) will be reported.
measure: Progression free survival (PFS)
time frame: From date of randomization until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 24 months.
description: The 2-year progression free survival of the whole group.
measure: Disease control rate (DCR)
time frame: To evaluate disease control rate every 8 weeks after the initiation of chemotherapy, up to 24 months.
description: Percentage of patients with disease control as assessed by best overall response (BOR) of either complete response(CR), partial remission(PR) or stable disease (SD) will be reported.
measure: Duration of Response (DoR)
time frame: First documented CR or PR, whichever is first recorded until the first assessment of PD, assessed up to 24 months.
description: The DoR applies only to patients whose BOR is either CR or PR. The duration is measured from the first documented response (CR or PR, whichever is first recorded) until the first assessment of Progressive Disease (PD).
measure: Overall survival (OS)
time frame: From date of randomization until the date of death from any cause or the date of last follow-up whichever came first, assessed up to 24 months.
description: The 2-year overall survival of the whole group.
measure: Survival rate (SR)
time frame: up to 24 months.
description: Survival probability of patients calculated according to Kaplan-Meier curve at either 1 or 2 year.
measure: Treatment related adverse events rate
time frame: From the enrollment to 30 days later of the last chemotherapy.
description: The incidence rate of treatment related adverse events of the whole group assessed by CTCAE v5.0.
arm group label: Gimatecan group
arm group type: Experimental
description: In Phase Ib study, patients will receive gimatecan at different dose level (0.4mg/m2, 0.6mg/m2,0.8mg/m2, oral, every 4 weeks) until progressive disease (PD).In Phase II study, patients will receive gimatecan at recommended phase II dose level.
intervention type: Drug
intervention name: Gimatecan
description: Patients will receive gimatecan orally at the recommended dose level on day 1-5 every 4 weeks.
arm group label: Gimatecan group
other name: ST1481
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: LIU XIAOQING, MD
role: Study Director
affiliation: The Fifth Medical Center of the Chinese PLA General Hospital
last name: LIU XIAOQING, MD
phone: 86-010-66947797
email: liuxiaoqing@csco.org.cn
facility: 
contact: 
country: China
citation: Hurwitz JL, McCoy F, Scullin P, Fennell DA. New advances in the second-line treatment of small cell lung cancer. Oncologist. 2009 Oct;14(10):986-94. doi: 10.1634/theoncologist.2009-0026. Epub 2009 Oct 9.
PMID: 19819917
citation: Owonikoko TK, Behera M, Chen Z, Bhimani C, Curran WJ, Khuri FR, Ramalingam SS. A systematic analysis of efficacy of second-line chemotherapy in sensitive and refractory small-cell lung cancer. J Thorac Oncol. 2012 May;7(5):866-72. doi: 10.1097/JTO.0b013e31824c7f4b.
PMID: 22722788
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Small Cell Lung Carcinoma