<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/NCT03231475</url>
  </required_header>
  <id_info>
    <org_study_id>SPH1188-11-101</org_study_id>
    <nct_id>NCT03231475</nct_id>
  </id_info>
  <brief_title>Phase I Study of SPH1188-11 in NSCLC</brief_title>
  <acronym>SPH1188-11</acronym>
  <official_title>Phase I, Open-label Study to Evaluate the Safety, Tolerance, Pharmacokinetics and Preliminary Efficacy of SPH1188-11 Tablets for the Treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC).</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Pharmaceuticals Holding Co., Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shanghai Pharmaceuticals Holding Co., Ltd</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>
      This study will treat patients with advanced NSCLC who have already received at least one&#xD;
      course of specific anti-cancer treatment but the tumour has started to re-grow following that&#xD;
      treatment. This is the first time this drug has ever been tested in patients, and so it will&#xD;
      help to understand what type of side effects may occur with the drug treatment, it will&#xD;
      measure the levels of drug in the body, it will also measure the anti-cancer activity. By&#xD;
      using these pieces of information together the best dose of this drug to use in further&#xD;
      clinical trials will be selected.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Phase I dose escalation study&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Board decision&#xD;
  </why_stopped>
  <start_date type="Actual">July 21, 2017</start_date>
  <completion_date type="Anticipated">March 31, 2022</completion_date>
  <primary_completion_date type="Actual">December 31, 2020</primary_completion_date>
  <phase>Phase 1</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>DLT and MTD of SPH1188-11</measure>
    <time_frame>28 days</time_frame>
    <description>Incidence and intensity of Adverse Events according to Common Toxicity Criteria (CTC version 4.03) associated with increasing doses of SPH1188-11, to find DLT and MTD</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tmax of SPH1188-11</measure>
    <time_frame>28 days</time_frame>
    <description>Evaluate the Tmax of SPH1188-11</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR of SPH1188-11</measure>
    <time_frame>52 weeks</time_frame>
    <description>Objective response rate(ORR) according to RECIST 1.1, ORR=CR+PR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS of SPH1188-11</measure>
    <time_frame>52 weeks</time_frame>
    <description>Progress free survival(PFS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DCR of SPH1188-11</measure>
    <time_frame>52 weeks</time_frame>
    <description>Disease control rate(DCR), DCR=CR+PR+SD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax of SPH1188-11</measure>
    <time_frame>28 days</time_frame>
    <description>Evaluate the Cmax of SPH1188-11</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC of SPH1188-11</measure>
    <time_frame>28 days</time_frame>
    <description>Evaluate the AUC of SPH1188-11</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T1/2 of SPH1188-11</measure>
    <time_frame>28 days</time_frame>
    <description>Evaluate the T1/2 of SPH1188-11</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>NSCLC Stage IIIB</condition>
  <condition>NSCLC Stage IV</condition>
  <arm_group>
    <arm_group_label>SPH1188-11</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SPH1188-11 dose escalation, 50mg/100mg/200mg/300mg/450mg/600mg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SPH1188-11</intervention_name>
    <description>qd.po</description>
    <arm_group_label>SPH1188-11</arm_group_label>
    <other_name>SPH1188</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. 18-70years old, male or female.&#xD;
&#xD;
          2. Histological or cytological confirmation diagnosis of Non Small Cell Lung&#xD;
             Cancer(NSCLC),Stage IIIBorIV, previous treatment with 1st EGFR-TKI, and/or previous&#xD;
             chemotherapy. Regardless of EGFR mutation status.&#xD;
&#xD;
          3. At least one measurable disease according to RECIST 1.1.&#xD;
&#xD;
          4. Life expectancy of at least 3 months.&#xD;
&#xD;
          5. Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.&#xD;
&#xD;
          6. Females should be using adequate contraceptive measures from the time of screening&#xD;
             until 3 months after discontinuing study treatment, should not be breast feeding and&#xD;
             must have a negative pregnancy test 7days prior to start of dosing. Males should be&#xD;
             willing to use barrier contraception during the trial and 3 months after discontinuing&#xD;
             study treatment.&#xD;
&#xD;
          7. Provision of signed and dated, written informed consent prior to any study specific&#xD;
             procedures, sampling and analyses.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Treatment with an EGFR-TKI(eg, erlotinib, gefitinib, icotinib) within 7 days or&#xD;
             approximately 5x half-life of study entry.&#xD;
&#xD;
          2. Previous treatment with 2nd EGFR-TKI or 3rd EGFR-TKI(eg, afatinib, osimertinib).&#xD;
&#xD;
          3. Any cytotoxic chemotherapy or anticancer drugs within 4 weeks of the first dose of&#xD;
             study treatment.&#xD;
&#xD;
          4. Major surgery(excluding placement of vascular access) within 4 weeks of the first dose&#xD;
             of study treatment.&#xD;
&#xD;
          5. Radiotherapy within 4 weeks of the first dose of study treatment.&#xD;
&#xD;
          6. Patients currently receiving(or unable to stop use at least 1 week prior to receiving&#xD;
             the first dose) medications or herbal supplements known to be potent inhibitors of&#xD;
             CYP3A4/CYP2D6, and/or potent inducers of CYP3A4/CYP2D6.&#xD;
&#xD;
          7. Laboratory values within 7 days of the first dose of study treatment:&#xD;
&#xD;
               -  Absolute neutrophil count&lt;1.5×10^9/L&#xD;
&#xD;
               -  Platelet count &lt;100×10^9/L&#xD;
&#xD;
               -  Haemoglobin&lt;90 g/L&#xD;
&#xD;
               -  Alanine aminotransferase&gt;2.5 times the upper limit of normal(ULN) if no&#xD;
                  demonstrable liver metastases or &gt;5 times ULN in the presence of liver&#xD;
                  metastases.&#xD;
&#xD;
               -  Aspartate aminotransferase&gt;2.5 times ULN if no demonstrable liver metastases or&#xD;
                  &gt;5 times ULN in the presence of liver metastases.&#xD;
&#xD;
               -  Total bilirubin&gt;1.5 times ULN if no liver metastases or &gt;3 times ULN in the&#xD;
                  presence of documented Gilbert's Syndrome(unconjugated hyperbilirubinaemia) or&#xD;
                  liver metastases.&#xD;
&#xD;
               -  Creatinine&gt;1.5 times ULN concurrent with creatinine clearance &lt;50ml/min(measured&#xD;
                  or calculated by Cockcroft and Gault equation); confirmation of creatinine&#xD;
                  clearance is only required when creatinine is&gt;1.5 times ULN.&#xD;
&#xD;
          8. Any unresolved toxicities from prior therapy greater than Common Terminology Criteria&#xD;
             for Adverse Events(CTCAE) grade 1 at the time of starting study treatment (except&#xD;
             alopecia and prior platinum-therapy related neuropathy)&#xD;
&#xD;
          9. Spinal cord compression or brain metastases unless asymptomatic, stable and not&#xD;
             requiring steroids for at least 4 weeks prior to start of study treatment.&#xD;
&#xD;
         10. Any evidence of severe or uncontrolled systemic diseases, including active bleeding,&#xD;
             active infection including hepatitis B(HBsAg+ and HBV-DNA+), hepatitis C and human&#xD;
             immunodeficiency virus(HIV).&#xD;
&#xD;
         11. Cardiac criteria: QTc&gt;480msec. LVEF&lt;50%. Any clinically important abnormalities in&#xD;
             rhythm, any factors that increase the risk of QTc prolongation or risk of arrhythmic&#xD;
             events such as heart failure, hypokalaemia, congenital long QT syndrome, family in&#xD;
             first degree relatives or any concomitant medication known to prolong the QT interval.&#xD;
&#xD;
         12. Past medical history of interstitial lung disease, drug-induced interstitial lung&#xD;
             disease, radiation pneumonitis which required steroid treatment, or any evidence of&#xD;
             clinically active interstitial lung disease.&#xD;
&#xD;
         13. Idiopathic pulmonary fibrosis.&#xD;
&#xD;
         14. Chronic gastrointestinal diseases, characterized by diarrhea.&#xD;
&#xD;
         15. Inability to swallow the formulated product or previous significant bowel resection&#xD;
             that would preclude adequate absorption of SPH1188-11.&#xD;
&#xD;
         16. History of Keratitis, ulcerative keratitis, severe xerophthalmia.&#xD;
&#xD;
         17. Previous or concomitant malignancies at other sites, except effectively treated&#xD;
             nonmelanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ or&#xD;
             effectively treated malignancy that has been in remission for more than 5 years and is&#xD;
             considered to be cured.&#xD;
&#xD;
         18. History of neurological or mental disorders, including epilepsy or dementia.&#xD;
&#xD;
         19. Allergy to the test drug or any excipient of the product.&#xD;
&#xD;
         20. Participate in other drug clinical trials within 4 weeks of the first dose of study&#xD;
             treatment.&#xD;
&#xD;
         21. Receiving any other anti-tumor therapy.&#xD;
&#xD;
         22. Women who are breast feeding or pregnant.&#xD;
&#xD;
         23. Judgment by the investigator that the patient should not participate in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>JunNing Cao, Master</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fudan University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fudan University Shanghai Cancer Center</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>June 6, 2017</study_first_submitted>
  <study_first_submitted_qc>July 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 27, 2017</study_first_posted>
  <last_update_submitted>October 31, 2021</last_update_submitted>
  <last_update_submitted_qc>October 31, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>NSCLC</keyword>
  <keyword>EGFR-TKI</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03231475
org study id: SPH1188-11-101
nct id: NCT03231475
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
This study will treat patients with advanced NSCLC who have already received at least one
      course of specific anti-cancer treatment but the tumour has started to re-grow following that
      treatment. This is the first time this drug has ever been tested in patients, and so it will
      help to understand what type of side effects may occur with the drug treatment, it will
      measure the levels of drug in the body, it will also measure the anti-cancer activity. By
      using these pieces of information together the best dose of this drug to use in further
      clinical trials will be selected.
Phase I dose escalation study
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: DLT and MTD of SPH1188-11
time frame: 28 days
description: Incidence and intensity of Adverse Events according to Common Toxicity Criteria (CTC version 4.03) associated with increasing doses of SPH1188-11, to find DLT and MTD
measure: Tmax of SPH1188-11
time frame: 28 days
description: Evaluate the Tmax of SPH1188-11
measure: ORR of SPH1188-11
time frame: 52 weeks
description: Objective response rate(ORR) according to RECIST 1.1, ORR=CR+PR
measure: PFS of SPH1188-11
time frame: 52 weeks
description: Progress free survival(PFS)
measure: DCR of SPH1188-11
time frame: 52 weeks
description: Disease control rate(DCR), DCR=CR+PR+SD
measure: Cmax of SPH1188-11
time frame: 28 days
description: Evaluate the Cmax of SPH1188-11
measure: AUC of SPH1188-11
time frame: 28 days
description: Evaluate the AUC of SPH1188-11
measure: T1/2 of SPH1188-11
time frame: 28 days
description: Evaluate the T1/2 of SPH1188-11
arm group label: SPH1188-11
arm group type: Experimental
description: SPH1188-11 dose escalation, 50mg/100mg/200mg/300mg/450mg/600mg
intervention type: Drug
intervention name: SPH1188-11
description: qd.po
arm group label: SPH1188-11
other name: SPH1188
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: JunNing Cao, Master
role: Principal Investigator
affiliation: Fudan University
facility: 
country: China
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
sharing ipd: No