<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/NCT03274882</url>
  </required_header>
  <id_info>
    <org_study_id>CL2-95005-003</org_study_id>
    <secondary_id>ISRCTN14228310</secondary_id>
    <nct_id>NCT03274882</nct_id>
  </id_info>
  <brief_title>Study of Efficacy and Safety of S 95005 (TAS-102) in Patients With Metastatic Colorectal Cancer Who Failed Standard Chemotherapies</brief_title>
  <official_title>Open-label Multicentre Confirmatory Study of Efficacy and Safety of S 95005 (TAS-102) in Patients With Metastatic Colorectal Cancer Who Are Refractory or Intolerant to Standard Chemotherapies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut de Recherches Internationales Servier</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>ADIR, a Servier Group company</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Servier</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the efficacy of S 95005 in patients with metastatic&#xD;
      colorectal cancer (mCRC) who are refractory or intolerant to standard chemotherapies in terms&#xD;
      of Progression-Free Survival rate at 2 months in the Russian population.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 3, 2017</start_date>
  <completion_date type="Actual">December 3, 2018</completion_date>
  <primary_completion_date type="Actual">December 31, 2017</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>Progression free survival (PFS) rate</measure>
    <time_frame>at 2 months</time_frame>
    <description>percentage of patients alive without investigator-assessed radiological disease progression according to RECIST 1.1 after 2 months</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS).</measure>
    <time_frame>Through study completion, an average of 12 weeks</time_frame>
    <description>based on Investigator review of the images according to RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate (ORR).</measure>
    <time_frame>Through study completion, an average of 12 weeks</time_frame>
    <description>based on Investigator review of the images according to RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>Through study completion, an average of 12 weeks</time_frame>
    <description>based on Investigator review of the images according to RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]</measure>
    <time_frame>Through study completion, an average of 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Abnormalities in laboratory tests (haematology, blood biochemistry and urinalysis) [safety and tolerability]</measure>
    <time_frame>Through study completion, an average of 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Abnormalities in physical examination and performance status (ECOG) [safety and tolerability]</measure>
    <time_frame>Through study completion, an average of 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Abnormalities in blood pressure [safety and tolerability]</measure>
    <time_frame>Through study completion, an average of 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Abnormalities in heart rate [safety and tolerability]</measure>
    <time_frame>Through study completion, an average of 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Abnormalities in body temperature [safety and tolerability]</measure>
    <time_frame>Through study completion, an average of 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Abnormalities in respiration rate [safety and tolerability]</measure>
    <time_frame>Through study completion, an average of 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Abnormalities in body weight [safety and tolerability]</measure>
    <time_frame>Through study completion, an average of 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Abnormalities in 12-leads ECG parameters [safety and tolerability]</measure>
    <time_frame>Through study completion, an average of 12 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Metastatic Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>S95005</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Film-coated tablet containing 15 mg of trifluridine and 7.065 mg of tipiracil hydrochloride, or 20 mg of trifluridine and 9.42 mg of tipiracil hydrochloride (with a molar ratio of 1:0.5) was administered at 35 mg/m²/dose orally twice a day, within 1 hour after completion of morning and evening meals, for 5 days on/2 days off, over 2 weeks, followed by a 14-day rest period. This treatment cycle was repeated every 4 weeks until treatment withdrawal criteria are met.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>S95005</intervention_name>
    <description>The treatment is given in open manner. It was administered until unacceptable toxicity according to the investigator, disease progression or patient withdrawal. If a patient discontinues study treatment for reasons other than radiologic disease progression (e.g., intolerable side effects), the patient was followed for tumour response until radiologic disease progression or initiation of new anticancer therapy (whichever occurs first).</description>
    <arm_group_label>S95005</arm_group_label>
    <other_name>TAS-102</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female aged ≥18 years of age&#xD;
&#xD;
          -  Has definitive histologically or cytologically confirmed adenocarcinoma of the colon&#xD;
             or rectum&#xD;
&#xD;
          -  Has received at least 2 prior regimens of standard chemotherapies for metastatic&#xD;
             colorectal cancer (including fluoropyrimidines, irinotecan and oxaliplatin and, if&#xD;
             accessible, an anti-VEGF monoclonal antibody and at least one of the anti-EGFR&#xD;
             monoclonal antibodies for RAS wild-type patients (if RAS mutation status was&#xD;
             evaluated)) and was refractory or intolerant to those chemotherapies&#xD;
&#xD;
          -  Has Eastern Cooperative Group (ECOG) performance status of 0 or 1&#xD;
&#xD;
          -  Has at least one measurable metastatic lesion(s)&#xD;
&#xD;
          -  Has adequate organ function&#xD;
&#xD;
          -  Female participants of childbearing potential and male participants with partners of&#xD;
             childbearing potential must agree to use a highly effective method of birth control&#xD;
             during the study and for 6 months after the discontinuation of study medication&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy, breastfeeding&#xD;
&#xD;
          -  Participation in another interventional study within 4 weeks prior to inclusion;&#xD;
             participation in non-interventional registries or epidemiological studies is allowed&#xD;
&#xD;
          -  Has previously received S95005 or history of allergic reaction attributed to compounds&#xD;
             of similar composition to S95005&#xD;
&#xD;
          -  Has a serious illness or medical condition(s) as described in the protocol&#xD;
&#xD;
          -  Has had certain other recent treatment e.g. major surgery, field radiation, anticancer&#xD;
             therapy, within the specified time frames prior to inclusion&#xD;
&#xD;
          -  Has unresolved toxicity of greater than or equal to Common Terminology Criteria for&#xD;
             Adverse Events (CTCAE) Grade 2 attributed to any prior therapies.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Vladimir MOISEENKO, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Saint Petersburg Clinical Scientific-Practical Center of Specialized Medical Care (Oncological)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Russian Cancer Research Center n.a. NN Blokhin (RCRC), Clinical Pharmacology and Chemotherapy department</name>
      <address>
        <city>Moscow</city>
        <zip>115478</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Petersburg Clinical Scientific-Practical Center of Special Medical Care (Oncology Center)</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>197758</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <link>
    <url>https://clinicaltrials.servier.com/wp-content/uploads/CL2-95005-003-laysummary-2019.06.27-1.pdf</url>
    <description>Lay Summary</description>
  </link>
  <link>
    <url>https://clinicaltrials.servier.com/wp-content/uploads/CL2-95005-003-anonymised-synopsis.pdf</url>
    <description>Results Summary</description>
  </link>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>August 2, 2017</study_first_submitted>
  <study_first_submitted_qc>September 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</study_first_posted>
  <last_update_submitted>May 9, 2023</last_update_submitted>
  <last_update_submitted_qc>May 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>metastatic</keyword>
  <keyword>colorectal</keyword>
  <keyword>cancer</keyword>
  <keyword>Lonsurf</keyword>
  <keyword>S95005</keyword>
  <keyword>Russia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Researchers can ask for a study protocol, patient-level and/or study-level clinical trial data including clinical study reports (CSRs).&#xD;
They can ask all interventional clinical studies:&#xD;
submitted for new medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).&#xD;
Where Servier or an affiliate are the Marketing Authorization Holders (MAH). The date of the first Marketing Authorization of the new medicine (or the new indication) in one of the EEA Member States will be considered within this scope.</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_time_frame>After Marketing Authorisation in EEA or US if the study is used for the approval.</ipd_time_frame>
    <ipd_access_criteria>Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.</ipd_access_criteria>
    <ipd_url>http://clinicaltrials.servier.com</ipd_url>
  </patient_data>
  <study_docs>
    <study_doc>
      <doc_type>Individual Participant Data Set</doc_type>
      <doc_url>https://clinicaltrials.servier.com/</doc_url>
    </study_doc>
    <study_doc>
      <doc_type>Study Protocol</doc_type>
      <doc_url>https://clinicaltrials.servier.com/</doc_url>
    </study_doc>
    <study_doc>
      <doc_type>Statistical Analysis Plan</doc_type>
      <doc_url>https://clinicaltrials.servier.com/</doc_url>
    </study_doc>
    <study_doc>
      <doc_type>Informed Consent Form</doc_type>
      <doc_url>https://clinicaltrials.servier.com/</doc_url>
    </study_doc>
    <study_doc>
      <doc_type>Clinical Study Report</doc_type>
      <doc_url>https://clinicaltrials.servier.com/</doc_url>
    </study_doc>
    <study_doc>
      <doc_type>Study-level clinical trial data</doc_type>
      <doc_url>https://clinicaltrials.servier.com/</doc_url>
    </study_doc>
  </study_docs>
  <!-- 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/NCT03274882
org study id: CL2-95005-003
secondary id: ISRCTN14228310
nct id: NCT03274882
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: Yes
The purpose of this study is to evaluate the efficacy of S 95005 in patients with metastatic
      colorectal cancer (mCRC) who are refractory or intolerant to standard chemotherapies in terms
      of Progression-Free Survival rate at 2 months in the Russian population.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression free survival (PFS) rate
time frame: at 2 months
description: percentage of patients alive without investigator-assessed radiological disease progression according to RECIST 1.1 after 2 months
measure: Progression-Free Survival (PFS).
time frame: Through study completion, an average of 12 weeks
description: based on Investigator review of the images according to RECIST 1.1
measure: Overall Response Rate (ORR).
time frame: Through study completion, an average of 12 weeks
description: based on Investigator review of the images according to RECIST 1.1
measure: Disease Control Rate (DCR)
time frame: Through study completion, an average of 12 weeks
description: based on Investigator review of the images according to RECIST 1.1
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
time frame: Through study completion, an average of 12 weeks
measure: Abnormalities in laboratory tests (haematology, blood biochemistry and urinalysis) [safety and tolerability]
time frame: Through study completion, an average of 12 weeks
measure: Abnormalities in physical examination and performance status (ECOG) [safety and tolerability]
time frame: Through study completion, an average of 12 weeks
measure: Abnormalities in blood pressure [safety and tolerability]
time frame: Through study completion, an average of 12 weeks
measure: Abnormalities in heart rate [safety and tolerability]
time frame: Through study completion, an average of 12 weeks
measure: Abnormalities in body temperature [safety and tolerability]
time frame: Through study completion, an average of 12 weeks
measure: Abnormalities in respiration rate [safety and tolerability]
time frame: Through study completion, an average of 12 weeks
measure: Abnormalities in body weight [safety and tolerability]
time frame: Through study completion, an average of 12 weeks
measure: Abnormalities in 12-leads ECG parameters [safety and tolerability]
time frame: Through study completion, an average of 12 weeks
arm group label: S95005
arm group type: Experimental
description: Film-coated tablet containing 15 mg of trifluridine and 7.065 mg of tipiracil hydrochloride, or 20 mg of trifluridine and 9.42 mg of tipiracil hydrochloride (with a molar ratio of 1:0.5) was administered at 35 mg/m²/dose orally twice a day, within 1 hour after completion of morning and evening meals, for 5 days on/2 days off, over 2 weeks, followed by a 14-day rest period. This treatment cycle was repeated every 4 weeks until treatment withdrawal criteria are met.
intervention type: Drug
intervention name: S95005
description: The treatment is given in open manner. It was administered until unacceptable toxicity according to the investigator, disease progression or patient withdrawal. If a patient discontinues study treatment for reasons other than radiologic disease progression (e.g., intolerable side effects), the patient was followed for tumour response until radiologic disease progression or initiation of new anticancer therapy (whichever occurs first).
arm group label: S95005
other name: TAS-102
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Vladimir MOISEENKO, Prof.
role: Principal Investigator
affiliation: Saint Petersburg Clinical Scientific-Practical Center of Specialized Medical Care (Oncological)
facility: 
facility: 
country: Russian Federation
url: https://clinicaltrials.servier.com/wp-content/uploads/CL2-95005-003-laysummary-2019.06.27-1.pdf
description: Lay Summary
url: https://clinicaltrials.servier.com/wp-content/uploads/CL2-95005-003-anonymised-synopsis.pdf
description: Results Summary
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
sharing ipd: Yes
ipd description: Researchers can ask for a study protocol, patient-level and/or study-level clinical trial data including clinical study reports (CSRs).
They can ask all interventional clinical studies:
submitted for new medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
Where Servier or an affiliate are the Marketing Authorization Holders (MAH). The date of the first Marketing Authorization of the new medicine (or the new indication) in one of the EEA Member States will be considered within this scope.
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 time frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
ipd access criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
ipd url: http://clinicaltrials.servier.com
study doc: 
study doc: 
study doc: 
study doc: 
study doc: 
study doc: 