xml: <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/NCT05975944</url>
    </required_header>
    <id_info>
      <org_study_id>SOS-001</org_study_id>
      <nct_id>NCT05975944</nct_id>
    </id_info>
    <brief_title>Study of Selinexor Combined With Olaparib in Relapsed/Refractory Extensive Stage Small Cell Lung Cancer</brief_title>
    <official_title>A Phase Ib/II Clinical Study Evaluating the Safety, Tolerability, and Efficacy of Selinexor Combined With Olaparib in the Treatment of Recurrent/Refractory Extensive-stage Small Cell Lung Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Tianjin Medical University Cancer Institute and Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Tianjin Medical University Cancer Institute and 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>
        This study is a multicenter, single arm, open, non-randomized, dose-escalation/ expansion&#xD;
        phase Ib/II clinical study. The dose-escalation part of phase Ib clinical trial was conducted&#xD;
        according to the Bayesian Optimal Interval Design (BOIN), with a total of three dose groups:&#xD;
        low, medium, and high. Dose level 1: Selinexor 40mg PO QW, Olaparib 150mg PO BID; Dose level&#xD;
        2: Selinexor 60mg PO QW, Olaparib 150mg PO BID; Dose level 3: Selinexor 80mg PO QW, Olaparib&#xD;
        150mg PO BID. The number of patients in each group is 3, with a maximum sample size of 9, to&#xD;
        evaluate the safety and effectiveness of the medication, and to provide a basis for&#xD;
        recommended phase II dose (RP2D). Eligible subjects received medication on the first day and&#xD;
        then entered a 21 day observation period of dose-limiting toxicity (DLT). DLT is defined as&#xD;
        the occurrence of level 3 non hematological toxicity or level 4 hematological toxicity.&#xD;
        Evaluate the efficacy every 6 weeks. In this study, an independent Data Safety Monitoring&#xD;
        Committee (DSMC) and an Independent Review Committee (IRC) were established to regularly&#xD;
        review the safety and effectiveness data of each research center, with the aim of protecting&#xD;
        subjects safety, ensuring the reliability of clinical trials and the objectivity of trial&#xD;
        results.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This study is a multicenter, single arm, open, non-randomized, dose-escalation/ expansion&#xD;
        phase Ib/II clinical study. The dose-escalation part of phase Ib clinical trial was conducted&#xD;
        according to the Bayesian Optimal Interval Design (BOIN), with a total of three dose groups:&#xD;
        low, medium, and high. Dose level 1: Selinexor 40mg PO QW, Olaparib 150mg PO BID; Dose level&#xD;
        2: Selinexor 60mg PO QW, Olaparib 150mg PO BID; Dose level 3: Selinexor 80mg PO QW, Olaparib&#xD;
        150mg PO BID. The number of patients in each group is 3, with a maximum sample size of 9, to&#xD;
        evaluate the safety and effectiveness of the medication, and to provide a basis for&#xD;
        recommended phase II dose (RP2D). Eligible subjects received medication on the first day and&#xD;
        then entered a 21 day observation period of dose-limiting toxicity (DLT). DLT is defined as&#xD;
        the occurrence of level 3 non hematological toxicity or level 4 hematological toxicity.&#xD;
        Evaluate the efficacy every 6 weeks. In this study, an independent Data Safety Monitoring&#xD;
        Committee (DSMC) and an Independent Review Committee (IRC) were established to regularly&#xD;
        review the safety and effectiveness data of each research center, with the aim of protecting&#xD;
        subjects safety, ensuring the reliability of clinical trials and the objectivity of trial&#xD;
        results.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">May 2024</completion_date>
    <primary_completion_date type="Anticipated">September 2023</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>MTD</measure>
      <time_frame>through study completion, an average of 1 year</time_frame>
      <description>MTD</description>
    </primary_outcome>
    <primary_outcome>
      <measure>ORR</measure>
      <time_frame>through study completion, an average of 1 year</time_frame>
      <description>ORR</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>DCR</measure>
      <time_frame>through study completion, an average of 1 year</time_frame>
      <description>DCR</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PFS</measure>
      <time_frame>through study completion, an average of 1 year</time_frame>
      <description>PFS</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>OS</measure>
      <time_frame>through study completion, an average of 1 year</time_frame>
      <description>OS</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">49</enrollment>
    <condition>Extensive-stage Small Cell Lung Cancer</condition>
    <arm_group>
      <arm_group_label>dose-escalation part of phase Ib clinical trial</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Dose level 1: Selinexor 40mg PO QW, Olaparib 150mg PO BID; Dose level 2: Selinexor 60mg PO QW, Olaparib 150mg PO BID; Dose level 3: Selinexor 80mg PO QW, Olaparib 150mg PO BID.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Selinexor，Olaparib</intervention_name>
      <description>Dose level 1: Selinexor 40mg PO QW, Olaparib 150mg PO BID; Dose level 2: Selinexor 60mg PO QW, Olaparib 150mg PO BID; Dose level 3: Selinexor 80mg PO QW, Olaparib 150mg PO BID.</description>
      <arm_group_label>dose-escalation part of phase Ib clinical trial</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  The diagnosis of SCLC is confirmed by histology or cytology, and according to VALSG&#xD;
               and AJCC8, the imaging diagnosis is extensive stage.&#xD;
  &#xD;
            -  The condition progresses after receiving at least 1 line of treatment, and within 6&#xD;
               months after the last treatment.&#xD;
  &#xD;
            -  The expected survival time is not less than 12 weeks.&#xD;
  &#xD;
            -  According to RECIST V1.1, there is at least one measurable lesion that has not&#xD;
               undergone radiation therapy.&#xD;
  &#xD;
            -  The Eastern Cooperative Oncology Group (ECOG) physical condition score is evaluated as&#xD;
               0 or 1.&#xD;
  &#xD;
            -  When screening, there is sufficient bone marrow reserve, and no blood transfusion or&#xD;
               hematopoietic stimulating factor treatment has been received 10 days before the test.&#xD;
               The definition is as follows: absolute neutrophil counts (ANC) ≥ 1.5×109/L, platelet&#xD;
               (PLT) ≥ 100×109/L and hemoglobin (HGB) ≥ 90g/L.&#xD;
  &#xD;
            -  Appropriate organ function during screening, meeting the following criteria: aspartate&#xD;
               aminotransferase (AST) ≤ 2.5×ULN (with liver metastasis ≤ 5×ULN); alanine&#xD;
               aminotransferase (ALT) ≤ 2.5ULN (with liver metastasis ≤ 5ULN); total serum bilirubin&#xD;
               ≤ 1.5×ULN (with tumor infiltration ≤ 3×ULN); serum creatinine (Scr) ≤ 1.5×ULN, or&#xD;
               creatinine clearance rate ≥ 60mL/min; international normalized ratio (INR) ≤ 1.5×ULN,&#xD;
               and activated partial thromboplastin time (APTT) ≤ 1.5×ULN; the urine pregnancy test&#xD;
               for women of childbearing age needs to be negative, and any male and female patients&#xD;
               with fertility must agree to use effective contraceptive methods throughout the entire&#xD;
               study process and for at least 1 year after treatment.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  During screening, patients with symptomatic central nervous system (CNS) metastasis&#xD;
               (asymptomatic CNS metastasis, or asymptomatic and stable condition after local&#xD;
               treatment for 4 weeks can be enrolled).&#xD;
  &#xD;
            -  Individuals with a history of central nervous system diseases before screening, such&#xD;
               as epilepsy, cerebral ischemia/bleeding, paralysis, aphasia, stroke, severe brain&#xD;
               injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome,&#xD;
               mental illness, or any autoimmune disease associated with central nervous system&#xD;
               involvement.&#xD;
  &#xD;
            -  Received chemotherapy, radiation therapy, immunotherapy, targeted therapy, biological&#xD;
               therapy, endocrine therapy within 4 weeks of screening, and was evaluated by the&#xD;
               researcher as not suitable for enrollment.&#xD;
  &#xD;
            -  The adverse reactions of previous anti-tumor treatments have not yet recovered to&#xD;
               level 1 (CTCAE5.0), except for toxicity that the researchers have determined to have&#xD;
               no safety risk, such as hair loss and level 2 peripheral neurotoxicity.&#xD;
  &#xD;
            -  Those who discontinue systemic hormone therapy for less than 72 hours before the first&#xD;
               administration, but are allowed to use physiological replacement doses of hormones&#xD;
               (such as prednisone &lt; 10mg/d or equivalent).&#xD;
  &#xD;
            -  Received organ/tissue transplantation before screening.&#xD;
  &#xD;
            -  Prior to screening, it was known that the patient had active systemic autoimmune&#xD;
               diseases and was currently undergoing treatment.&#xD;
  &#xD;
            -  Those who meet any of the following conditions during screening: hepatitis B surface&#xD;
               antigen (HBsAg) is positive, and the copy number of HBV DNA is greater than the&#xD;
               measurable lower limit; hepatitis C antibody (HCV Ab) is positive; treponema pallidum&#xD;
               antibody (TP-Ab) is positive; HIV antibody is positive; The copy numbers of EBV-DNA&#xD;
               and CMV-DNA are higher than the measurable lower limit.&#xD;
  &#xD;
            -  Individuals who have undergone major surgery or experienced significant trauma within&#xD;
               4 weeks prior to screening, or who require elective surgery during the trial period,&#xD;
               have been evaluated by the researchers as unsuitable for inclusion.&#xD;
  &#xD;
            -  Within 2 years prior to screening or currently suffering from other malignant tumors.&#xD;
  &#xD;
            -  When screening, the heart meets any of the following conditions: New York Heart&#xD;
               Association (NYHA) ≥ Level II, Left Ventricular Ejection Fraction (LVEF) ≤ 50% (ECHO);&#xD;
               Hypertension (systolic blood pressure ≥ 140mmHg and/or diastolic blood pressure ≥&#xD;
               90mmHg) or pulmonary hypertension that has not been controlled after standardized&#xD;
               treatment; Acute coronary syndrome, congestive heart failure, aortic dissection,&#xD;
               stroke, or other Grade 3 or higher cardiovascular and cerebrovascular events occurred&#xD;
               within 6 months before the first administration; valvular disease with clinical&#xD;
               significance; There are serious cardiac rhythm or conduction abnormalities, such as&#xD;
               ventricular arrhythmias that require clinical intervention, II-III degree&#xD;
               atrioventricular block, etc.&#xD;
  &#xD;
            -  Patients with tumor involving the atrium or ventricle during screening.&#xD;
  &#xD;
            -  When screening, there are clinical emergencies that require urgent treatment due to&#xD;
               tumor obstruction or compression (such as intestinal obstruction or vascular&#xD;
               compression).&#xD;
  &#xD;
            -  Individuals with active bleeding during screening.&#xD;
  &#xD;
            -  Those with a history of deep vein thrombosis or pulmonary embolism within 6 months&#xD;
               before screening.&#xD;
  &#xD;
            -  Individuals who have received live vaccines within 6 weeks before screening.&#xD;
  &#xD;
            -  Subjects with uncontrolled systemic bacterial, viral, or fungal infections after&#xD;
               optimal treatment.&#xD;
  &#xD;
            -  Participated in other interventional clinical studies within 4 weeks before the first&#xD;
               administration.&#xD;
  &#xD;
            -  Individuals with poor adherence or those who are deemed unsuitable for clinical trials&#xD;
               by researchers due to other reasons.&#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>huang ding zhi, M.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Tianjin Medical University Cancer Institute and Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>huang ding zhi, M.D.</last_name>
      <phone>+86-22-23340123-3200</phone>
      <email>dingzhih72@163.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>huang ding zhi, M.D.</last_name>
      <email>dingzhih72@163.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Tianjin Medical University Cancer Institute and Hospital</name>
        <address>
          <city>Tianjin</city>
          <zip>300060</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Huang Ding Zhi, PHD</last_name>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <results_reference>
      <citation>Wang J, Sun T, Meng Z, Wang L, Li M, Chen J, Qin T, Yu J, Zhang M, Bie Z, Dong Z, Jiang X, Lin L, Zhang C, Liu Z, Jiang R, Yang G, Li L, Zhang Y, Huang D. XPO1 inhibition synergizes with PARP1 inhibition in small cell lung cancer by targeting nuclear transport of FOXO3a. Cancer Lett. 2021 Apr 10;503:197-212. doi: 10.1016/j.canlet.2021.01.008. Epub 2021 Jan 23.</citation>
      <PMID>33493586</PMID>
    </results_reference>
    <verification_date>May 2023</verification_date>
    <study_first_submitted>May 28, 2023</study_first_submitted>
    <study_first_submitted_qc>July 27, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 4, 2023</study_first_posted>
    <last_update_submitted>July 27, 2023</last_update_submitted>
    <last_update_submitted_qc>July 27, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 4, 2023</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>Lung Neoplasms</mesh_term>
      <mesh_term>Small Cell Lung Carcinoma</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Olaparib</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>De-identified individul participant data for all primary and secondary outcome measures will be made available.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
      <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
      <ipd_info_type>Analytic Code</ipd_info_type>
      <ipd_time_frame>Data will be available within 6 months of study completion</ipd_time_frame>
      <ipd_access_criteria>Data access requests will be reviewed by an external indepentent Review Panel. Requesdtors will be required to sign a Data Access Agreement.</ipd_access_criteria>
      <ipd_url>http://www.cttq.com/</ipd_url>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05975944
  org study id: SOS-001
  nct id: NCT05975944
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  This study is a multicenter, single arm, open, non-randomized, dose-escalation/ expansion
        phase Ib/II clinical study. The dose-escalation part of phase Ib clinical trial was conducted
        according to the Bayesian Optimal Interval Design (BOIN), with a total of three dose groups:
        low, medium, and high. Dose level 1: Selinexor 40mg PO QW, Olaparib 150mg PO BID; Dose level
        2: Selinexor 60mg PO QW, Olaparib 150mg PO BID; Dose level 3: Selinexor 80mg PO QW, Olaparib
        150mg PO BID. The number of patients in each group is 3, with a maximum sample size of 9, to
        evaluate the safety and effectiveness of the medication, and to provide a basis for
        recommended phase II dose (RP2D). Eligible subjects received medication on the first day and
        then entered a 21 day observation period of dose-limiting toxicity (DLT). DLT is defined as
        the occurrence of level 3 non hematological toxicity or level 4 hematological toxicity.
        Evaluate the efficacy every 6 weeks. In this study, an independent Data Safety Monitoring
        Committee (DSMC) and an Independent Review Committee (IRC) were established to regularly
        review the safety and effectiveness data of each research center, with the aim of protecting
        subjects safety, ensuring the reliability of clinical trials and the objectivity of trial
        results.
  This study is a multicenter, single arm, open, non-randomized, dose-escalation/ expansion
        phase Ib/II clinical study. The dose-escalation part of phase Ib clinical trial was conducted
        according to the Bayesian Optimal Interval Design (BOIN), with a total of three dose groups:
        low, medium, and high. Dose level 1: Selinexor 40mg PO QW, Olaparib 150mg PO BID; Dose level
        2: Selinexor 60mg PO QW, Olaparib 150mg PO BID; Dose level 3: Selinexor 80mg PO QW, Olaparib
        150mg PO BID. The number of patients in each group is 3, with a maximum sample size of 9, to
        evaluate the safety and effectiveness of the medication, and to provide a basis for
        recommended phase II dose (RP2D). Eligible subjects received medication on the first day and
        then entered a 21 day observation period of dose-limiting toxicity (DLT). DLT is defined as
        the occurrence of level 3 non hematological toxicity or level 4 hematological toxicity.
        Evaluate the efficacy every 6 weeks. In this study, an independent Data Safety Monitoring
        Committee (DSMC) and an Independent Review Committee (IRC) were established to regularly
        review the safety and effectiveness data of each research center, with the aim of protecting
        subjects safety, ensuring the reliability of clinical trials and the objectivity of trial
        results.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: MTD
  time frame: through study completion, an average of 1 year
  description: MTD
  measure: ORR
  time frame: through study completion, an average of 1 year
  description: ORR
  measure: DCR
  time frame: through study completion, an average of 1 year
  description: DCR
  measure: PFS
  time frame: through study completion, an average of 1 year
  description: PFS
  measure: OS
  time frame: through study completion, an average of 1 year
  description: OS
  arm group label: dose-escalation part of phase Ib clinical trial
  arm group type: Experimental
  description: Dose level 1: Selinexor 40mg PO QW, Olaparib 150mg PO BID; Dose level 2: Selinexor 60mg PO QW, Olaparib 150mg PO BID; Dose level 3: Selinexor 80mg PO QW, Olaparib 150mg PO BID.
  intervention type: Drug
  intervention name: Selinexor，Olaparib
  description: Dose level 1: Selinexor 40mg PO QW, Olaparib 150mg PO BID; Dose level 2: Selinexor 60mg PO QW, Olaparib 150mg PO BID; Dose level 3: Selinexor 80mg PO QW, Olaparib 150mg PO BID.
  arm group label: dose-escalation part of phase Ib clinical trial
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: huang ding zhi, M.D.
  role: Principal Investigator
  affiliation: Tianjin Medical University Cancer Institute and Hospital
  last name: huang ding zhi, M.D.
  phone: +86-22-23340123-3200
  email: dingzhih72@163.com
  last name: huang ding zhi, M.D.
  email: dingzhih72@163.com
  facility: 
  status: Recruiting
  contact: 
  country: China
  citation: Wang J, Sun T, Meng Z, Wang L, Li M, Chen J, Qin T, Yu J, Zhang M, Bie Z, Dong Z, Jiang X, Lin L, Zhang C, Liu Z, Jiang R, Yang G, Li L, Zhang Y, Huang D. XPO1 inhibition synergizes with PARP1 inhibition in small cell lung cancer by targeting nuclear transport of FOXO3a. Cancer Lett. 2021 Apr 10;503:197-212. doi: 10.1016/j.canlet.2021.01.008. Epub 2021 Jan 23.
  PMID: 33493586
  responsible party type: Sponsor
  mesh term: Lung Neoplasms
  mesh term: Small Cell Lung Carcinoma
  mesh term: Olaparib
  sharing ipd: Yes
  ipd description: De-identified individul participant data for all primary and secondary outcome measures will be made available.
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd info type: Informed Consent Form (ICF)
  ipd info type: Clinical Study Report (CSR)
  ipd info type: Analytic Code
  ipd time frame: Data will be available within 6 months of study completion
  ipd access criteria: Data access requests will be reviewed by an external indepentent Review Panel. Requesdtors will be required to sign a Data Access Agreement.
  ipd url: http://www.cttq.com/