<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/NCT04418648</url>
  </required_header>
  <id_info>
    <org_study_id>2019-FXY-243</org_study_id>
    <nct_id>NCT04418648</nct_id>
  </id_info>
  <brief_title>Study of Toripalimab for Limited-Stage Small Cell Lung Cancer Following Concurrent Chemoradiotherapy</brief_title>
  <official_title>A Phase II, Randomised Study of Toripalimab as Consolidation Therapy in Patients With Limited-Stage Small Cell Lung Cancer Who Have Not Progressed Following Concurrent Chemoradiotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The First Affiliated Hospital of Guangzhou Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Guangzhou Panyu Central Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The phase II, randomised study is to explore the efficacy and safety of toripalimab as&#xD;
      consolidation therapy in patients with limited-stage small cell lung cancer who have not&#xD;
      progressed following concurrent chemoradiation therapy&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 1, 2020</start_date>
  <completion_date type="Anticipated">May 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">May 31, 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel 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>2 years</time_frame>
    <description>Time from the date of randomisation until death from any cause or first documented disease progression determined by RECISIT v1.1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>2 years</time_frame>
    <description>Time from the date of randomisation until death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate</measure>
    <time_frame>2 years</time_frame>
    <description>Best overall response (CR or PR) rate determined by RECISIT v1.1 across all assessment time-points during the period from randomisation to termination of protocol specific treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response</measure>
    <time_frame>2 years</time_frame>
    <description>Time from the date of first documented response of CR or PR until first documented progression or death, determined by RECISIT v1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Event</measure>
    <time_frame>2 years</time_frame>
    <description>Number of participants with treatment-related adverse events determined by CTCAE v4.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life (EORTC QLQ-C30)</measure>
    <time_frame>2 years</time_frame>
    <description>Quality of life score assessed by Quality of Life Questionnaire-Core 30 proposed by The European O-rganization for Reasearch and Treatment of Cancer. EORTC QLQ-C30 contained 30 items. Items 29 and 30 are rated on a scale of 1 to 7. The other items are divided into four grades: totally not, a little bit, a lot and very much, and scored on a scale of 1 to 4. For functional and overall health domain, a higher score refers to a better life quality; for symptom domain, a higher score refers to a worse life quality.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life (EORTC QLQ-LC13)</measure>
    <time_frame>2 years</time_frame>
    <description>Quality of life score assessed by Quality of Life Questionnare-Lung Cancer 13 proposed by The European O-rganization for Reasearch and Treatment of Cancer. EORTC QLQ-LC13 contained 13 items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. Each item is scored on a scale 0 to 100, where 0 indicates no symptoms and 100 indicates the worst possible symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ECOG performance status</measure>
    <time_frame>2 years</time_frame>
    <description>Performance status score assessed by Zubrod-ECOG-WHO method, range 0-5. A higher score refers to a worse quality of life.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">170</enrollment>
  <condition>Small Cell Lung Cancer Limited Stage</condition>
  <arm_group>
    <arm_group_label>Toripalimab Consolidation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients in experimental group will receive toripalimab consolidation (240 mg) via iv infusion Q3W.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Observation</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients in this group will receive observation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Toripalimab</intervention_name>
    <description>Toripalimab consolidation (240 mg) via iv infusion once every 3 weeks. Administration of toripalimab will commence on Day 1 following randomisation to toripalimab after confirmation of eligibility and will continue on a Q3W schedule for a maximum duration of 6 months.</description>
    <arm_group_label>Toripalimab Consolidation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Provision of signed, written and dated informed consent prior to any study specific&#xD;
             procedures;&#xD;
&#xD;
          -  Male or female aged 18-75 years;&#xD;
&#xD;
          -  Histologically- or cytologically-documented SCLC;&#xD;
&#xD;
          -  Stage I-III (AJCC/UICC 8th TNM Staging), with all lesions can be included in a&#xD;
             tolerable radiotherapy field (limited-stage);&#xD;
&#xD;
          -  Previous thoracic radiotherapy (45 Gy twice daily or 60-66 Gy once daily) and&#xD;
             concurrent etoposide and platinum for four cycles; Dose coverage ≥ 85% of PTV-GTV.&#xD;
             Radiotherapy started before the completion of the third cycle of chemotherapy;&#xD;
&#xD;
          -  CR, PR or SD after concurrent chemoradiotherapy (RECIST v1.1);&#xD;
&#xD;
          -  PCI is allowed and should be completed within 90 days after the completion of&#xD;
             chemoradiotherapy;&#xD;
&#xD;
          -  Randommization shoud be completed within 90 days after the completion of&#xD;
             chemoradiotherapy;&#xD;
&#xD;
          -  Life expectancy ≥12 weeks;&#xD;
&#xD;
          -  World Health Organization (WHO) Performance Status of 0 or 1;&#xD;
&#xD;
          -  Evidence of post-menopausal status, or negative urinary or serum pregnancy test for&#xD;
             female pre-menopausal patients within 7 days before the use of study drug (HCG has a&#xD;
             minimum sensitivity of 25 IU/L or equivalent);&#xD;
&#xD;
          -  Women must be non-breastfeeding;&#xD;
&#xD;
          -  Women of reproductive age (WOCBP) must agree to comply with the contraceptive method&#xD;
             during the study toripalimab treatment and for a period of 3 months following the last&#xD;
             administration of the study treatment (i.e., 30 days [ovulation cycle] plus&#xD;
             approximately 5 half-lives of the study drug);&#xD;
&#xD;
          -  Men who have sex with WOCBP must agree to comply with the contraceptive method during&#xD;
             the study nivolumab treatment and for 5 months after the last administration of the&#xD;
             study treatment (i.e. 90 days [sperm renewal cycle] plus approximately 5 half-lives of&#xD;
             the study drug);&#xD;
&#xD;
          -  Spermless men do not have to comply with contraceptive requirements. WOCBP who&#xD;
             continues to be asexual with the opposite sex does not have to comply with&#xD;
             contraceptive requirements, but must still undergo the pregnancy tests described in&#xD;
             this section;&#xD;
&#xD;
          -  Adequate organ and marrow function as defined below:&#xD;
&#xD;
               1. Forced expiratory volume in 1 second (FEV1) ≥ 800ml;&#xD;
&#xD;
               2. Absolute neutrophil count ≥1.5 x 10^9/L (1500 per mm3);&#xD;
&#xD;
               3. Platelets ≥100 x 10^9/L (100,000 per mm3);&#xD;
&#xD;
               4. Haemoglobin ≥ 9.0 g/dL (5.59 mmol/L);&#xD;
&#xD;
               5. Serum creatinine clearance (CL) ≥ 50 mL/min by the Cockcroft-Gault formula&#xD;
                  (Cockcroft and -Gault 1976);&#xD;
&#xD;
               6. Serum bilirubin ≤1.5 x upper limit of normal (ULN);&#xD;
&#xD;
               7. Aspartate Transaminase (AST) and Alanine Transaminase (ALT) ≤ 2.5 x ULN.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Concurrent enrolment in another clinical study, unless it is an observational&#xD;
             (non-interventional) clinical study;&#xD;
&#xD;
          -  Mixed small cell and non-small cell lung cancer histology;&#xD;
&#xD;
          -  Extensive-stage SCLC;&#xD;
&#xD;
          -  Histologically-confirmed malignant pleural or pericardial effusion;&#xD;
&#xD;
          -  Sequential chemoradiotherapy, or radiotherapy did not start before the completion of&#xD;
             the third cycle of chemotherapy;&#xD;
&#xD;
          -  Progressive disease after concurrent chemoradiotherapy (RECIST v1.1) and before&#xD;
             randomization;&#xD;
&#xD;
          -  Prior use of surgery, radiotherapy or chemotherapy for SCLC, with the exceptions of&#xD;
             thoracic concurrent chemoradiotherapy and PCI;&#xD;
&#xD;
          -  Any unresolved toxicity CTCAE &gt;Grade 2 from the prior chemoradiation therapy will be&#xD;
             excluded from randomization;&#xD;
&#xD;
          -  Patients with Grade ≥2 pneumonitis from prior chemoradiation therapy will be excluded&#xD;
             from randomization;&#xD;
&#xD;
          -  Current or prior use of immunosuppressive medication within 28 days before the first&#xD;
             dose of toripalimab, with the exceptions of intranasal and inhaled corticosteroids or&#xD;
             systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of&#xD;
             prednisone, or an equivalent corticosteroid. Systemic steroid administration required&#xD;
             to manage toxicities arising from radiation therapy delivered as part of the previous&#xD;
             chemoradiotherapy for SCLC is allowed;&#xD;
&#xD;
          -  Prior exposure to any anti-programmed cell death protein(PD)-1 or anti-PD-L1 antibody;&#xD;
&#xD;
          -  Recent major surgery within 4 weeks prior to entry into the study (excluding the&#xD;
             placement of vascular access);&#xD;
&#xD;
          -  Active or prior documented autoimmune disease within the past 2 years including, but&#xD;
             not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus&#xD;
             erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid&#xD;
             antibody syndrome, Wegener's granuloma, Sjogren's syndrome, Guillain Barre syndrome or&#xD;
             multiple sclerosis;&#xD;
&#xD;
          -  History of primary immunodeficiency;&#xD;
&#xD;
          -  History of organ transplant that requires therapeutic immunosuppression;&#xD;
&#xD;
          -  Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3&#xD;
             electrocardiograms (ECGs) using Bazett's Correction;&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable&#xD;
             angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active&#xD;
             bleeding diatheses, hepatitis C , human immunodeficiency virus (HIV), or patients with&#xD;
             positive HBsAg and HBV-DNA &gt; 500 IU/ml, or psychiatric illness/social situations that&#xD;
             would limit compliance with study requirements or compromise the ability of the&#xD;
             patient to give written informed consent;&#xD;
&#xD;
          -  Known history of tuberculosis;&#xD;
&#xD;
          -  Receipt of live attenuated vaccination within 30 days prior to study entry;&#xD;
&#xD;
          -  History of another primary malignancy within 5 years prior to study entry, except for&#xD;
             adequately treated basal or squamous cell carcinoma of the skin or cancer of the&#xD;
             cervix in situ, breast intraductal carcinoma in situ or localized prostate cancer;&#xD;
&#xD;
          -  Female patients who are pregnant, breast-feeding or male or female patients of&#xD;
             reproductive potential who are not employing an effective method of birth control;&#xD;
&#xD;
          -  Any condition that, in the opinion of the investigator, would interfere with&#xD;
             evaluation of the toripalimab or interpretation of patient safety or study results;&#xD;
&#xD;
          -  Any condition that, in the opinion of the investigator, not suitable for study entry.&#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_contact>
    <last_name>Bo Qiu</last_name>
    <phone>+86-020-87343031</phone>
    <email>qiubo@sysucc.org.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Hui Liu</last_name>
    <phone>+86-020-87343031</phone>
    <email>liuhui@sysucc.org.cn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Sun Yat-sen University Cancer Center</name>
      <address>
        <city>Guang Zhou</city>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bo Qiu</last_name>
      <phone>+862087343031</phone>
      <email>qiubo@sysucc.org.cn</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>May 25, 2020</study_first_submitted>
  <study_first_submitted_qc>June 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 5, 2020</study_first_posted>
  <last_update_submitted>November 25, 2022</last_update_submitted>
  <last_update_submitted_qc>November 25, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>Hui Liu</investigator_full_name>
    <investigator_title>Prof.</investigator_title>
  </responsible_party>
  <keyword>Consolidation therapy</keyword>
  <keyword>Toripalimab</keyword>
  <keyword>Concurrent chemoradiotherapy</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/NCT04418648
org study id: 2019-FXY-243
nct id: NCT04418648
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
The phase II, randomised study is to explore the efficacy and safety of toripalimab as
      consolidation therapy in patients with limited-stage small cell lung cancer who have not
      progressed following concurrent chemoradiation therapy
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free Survival
time frame: 2 years
description: Time from the date of randomisation until death from any cause or first documented disease progression determined by RECISIT v1.1
measure: Overall Survival
time frame: 2 years
description: Time from the date of randomisation until death from any cause
measure: Objective Response Rate
time frame: 2 years
description: Best overall response (CR or PR) rate determined by RECISIT v1.1 across all assessment time-points during the period from randomisation to termination of protocol specific treatment
measure: Duration of Response
time frame: 2 years
description: Time from the date of first documented response of CR or PR until first documented progression or death, determined by RECISIT v1.1
measure: Adverse Event
time frame: 2 years
description: Number of participants with treatment-related adverse events determined by CTCAE v4.0
measure: Quality of Life (EORTC QLQ-C30)
time frame: 2 years
description: Quality of life score assessed by Quality of Life Questionnaire-Core 30 proposed by The European O-rganization for Reasearch and Treatment of Cancer. EORTC QLQ-C30 contained 30 items. Items 29 and 30 are rated on a scale of 1 to 7. The other items are divided into four grades: totally not, a little bit, a lot and very much, and scored on a scale of 1 to 4. For functional and overall health domain, a higher score refers to a better life quality; for symptom domain, a higher score refers to a worse life quality.
measure: Quality of Life (EORTC QLQ-LC13)
time frame: 2 years
description: Quality of life score assessed by Quality of Life Questionnare-Lung Cancer 13 proposed by The European O-rganization for Reasearch and Treatment of Cancer. EORTC QLQ-LC13 contained 13 items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. Each item is scored on a scale 0 to 100, where 0 indicates no symptoms and 100 indicates the worst possible symptoms.
measure: ECOG performance status
time frame: 2 years
description: Performance status score assessed by Zubrod-ECOG-WHO method, range 0-5. A higher score refers to a worse quality of life.
arm group label: Toripalimab Consolidation
arm group type: Experimental
description: Patients in experimental group will receive toripalimab consolidation (240 mg) via iv infusion Q3W.
arm group label: Observation
arm group type: No Intervention
description: Patients in this group will receive observation.
intervention type: Drug
intervention name: Toripalimab
description: Toripalimab consolidation (240 mg) via iv infusion once every 3 weeks. Administration of toripalimab will commence on Day 1 following randomisation to toripalimab after confirmation of eligibility and will continue on a Q3W schedule for a maximum duration of 6 months.
arm group label: Toripalimab Consolidation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Bo Qiu
phone: +86-020-87343031
email: qiubo@sysucc.org.cn
last name: Hui Liu
phone: +86-020-87343031
email: liuhui@sysucc.org.cn
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Hui Liu
investigator title: Prof.
mesh term: Lung Neoplasms
mesh term: Small Cell Lung Carcinoma