<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/NCT04489173</url>
  </required_header>
  <id_info>
    <org_study_id>BOOG 2019-01</org_study_id>
    <nct_id>NCT04489173</nct_id>
  </id_info>
  <brief_title>TAS102 in Patients With ER-positive, HER2-negative Advanced Breast Cancer</brief_title>
  <acronym>TIBET</acronym>
  <official_title>A Phase 2 Study of Trifluridine/Tipiracil in Patients With ER-positive, HER2-negative Advanced Breast Cancer That Previously Received Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Borstkanker Onderzoek Groep</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Erasmus Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>UMC Utrecht</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Servier</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>BOOG Study Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Borstkanker Onderzoek Groep</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 is a multicenter phase 2 study evaluating the efficacy and safety of&#xD;
      trifluridine/tipiracil in women with metastatic or locally advanced breast cancer not&#xD;
      amenable to curative treatment by surgery or radiotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Multicenter phase 2 study evaluating the efficacy and safety of trifluridine/tipiracil in&#xD;
      women with metastatic or locally advanced breast cancer not amenable to curative treatment by&#xD;
      surgery or radiotherapy. This study will be conducted under the sponsorship of BOOG,&#xD;
      Amsterdam, NL.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      To evaluate the efficacy of trifluridine/tipiracil by determination of the percentage of&#xD;
      patients being progression free at 8 weeks on trifluridine/tipiracil prescribed for&#xD;
      ER-positive, HER2-negative advanced breast cancer patients previously treated with a taxane&#xD;
      and capecitabine.&#xD;
&#xD;
      Endpoints:&#xD;
&#xD;
      Progression-free survival Response rate CR/PR at 16 weeks Adverse events Translational&#xD;
      research on biological factors that may be of influence on the outcome of treatment QoL&#xD;
&#xD;
      Main eligibility criteria:&#xD;
&#xD;
      Metastatic Her2 negative, ER-positive breast cancer patients that progressed on, or after&#xD;
      treatment with Capecitabine. Previous treatment with Taxanes is obligatory. Adequate&#xD;
      hematology, liver and renal function tests.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 25, 2020</start_date>
  <completion_date type="Anticipated">July 2024</completion_date>
  <primary_completion_date type="Anticipated">September 2023</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>
    <intervention_model_description>Multicenter, single arm, phase 2 study evaluating the efficacy and safety of trifluridine/tipiracil in women with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy.&#xD;
Study medication should be started within 3 days after completion of screening and continue until a study treatment discontinuation criterion is met.&#xD;
Trifluridine/tipiracil will be administered orally BID on days 1 through 5, with the first dose administered in the morning of day 1 of each cycle and the last dose administered in the evening of day 5, followed by a recovery period from day 6 through day 7. Trifluridine/tipiracil will be administered orally BID on days 8 through 12, with the first dose administered in the morning of day 8 of each cycle and the last dose administered in the evening of day 12, followed by a recovery period from day 13 through day 28. Each cycle will be 28 days.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>16 weeks</time_frame>
    <description>Response rate CR/PR</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>every 4 weeks</time_frame>
    <description>CTCAE version 4.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>QoL</measure>
    <time_frame>32 weeks</time_frame>
    <description>Quality of Life questionnaire EORTC QLQ-C30</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Breast Neoplasm</condition>
  <condition>Chemotherapy Effect</condition>
  <arm_group>
    <arm_group_label>Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment with TAS102</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>trifluridine/tipiracil</intervention_name>
    <description>Study medication should be started within 3 days after completion of screening and continue until a study treatment discontinuation criterion is met.&#xD;
Trifluridine/tipiracil will be administered orally BID on days 1 through 5, with the first dose administered in the morning of day 1 of each cycle and the last dose administered in the evening of day 5, followed by a recovery period from day 6 through day 7. Trifluridine/tipiracil will be administered orally BID on days 8 through 12, with the first dose administered in the morning of day 8 of each cycle and the last dose administered in the evening of day 12, followed by a recovery period from day 13 through day 28. Each cycle will be 28 days.</description>
    <arm_group_label>Treatment</arm_group_label>
    <other_name>Lonsurf, TAS102</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult women(≥ 18 years of age) with proven diagnosis of metastatic or locally advanced&#xD;
             breast cancer not amenable to curative treatment by surgery or radiotherapy&#xD;
&#xD;
          2. Documented ER positive (10%) and/or PR positive (10%) and HER2 negative metastatic&#xD;
             breast cancer&#xD;
&#xD;
          3. Progressive disease based on imaging&#xD;
&#xD;
          4. Women previously treated with capecitabine (in metastatic setting), and a maximum of&#xD;
             two other lines of chemotherapy including a taxane either in the (neo)adjuvant or&#xD;
             metastatic setting.&#xD;
&#xD;
          5. Evaluable disease as defined per RECIST v.1.1 (see Appendix B). Tumor lesions&#xD;
             previously irradiated or subjected to other locoregional therapy will only be deemed&#xD;
             measurable if disease progression at the treated site after completion of therapy is&#xD;
             clearly documented.&#xD;
&#xD;
          6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1&#xD;
&#xD;
          7. Life expectancy of ≥ 12 weeks&#xD;
&#xD;
          8. Willing and able to comply with scheduled visits and study procedures&#xD;
&#xD;
          9. Adequate organ, bone marrow and coagulation function as shown by:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1.5 ×109/L&#xD;
&#xD;
               -  Platelets ≥ 75 ×109/L&#xD;
&#xD;
               -  Hemoglobin (Hgb) ≥ 5.6 mmol/L&#xD;
&#xD;
               -  Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5&#xD;
                  ULN (or ≤ 5 if hepatic metastases are present)&#xD;
&#xD;
               -  Total serum bilirubin ≤ 1.5 × ULN (≤ 3 × ULN for patients known to have Gilbert&#xD;
                  Syndrome)&#xD;
&#xD;
               -  Creatinine clearance ≥60 ml/min&#xD;
&#xD;
         10. Written informed consent obtained before any screening procedure and according to&#xD;
             local guidelines.&#xD;
&#xD;
         11. Resolution of all acute toxic effects of prior anti-cancer therapy or surgical&#xD;
             procedures to NCI CTCAE version 4.0 Grade ≤1, except alopecia or other toxicities not&#xD;
             considered a safety risk for the patient at investigator's discretion.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ&#xD;
             hybridization positive) and ER-negative patients are not eligible&#xD;
&#xD;
          2. No more than two lines of chemotherapy for advanced disease&#xD;
&#xD;
          3. Resolution of side-effects from previous chemotherapy &gt; grade 1 (except for alopecia)&#xD;
&#xD;
          4. Radiotherapy within four weeks prior to enrollment is not allowed except in case of&#xD;
             localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture&#xD;
             which can then be completed within two weeks prior to enrollment. Patients must have&#xD;
             recovered from radiotherapy toxicities prior to enrollment.&#xD;
&#xD;
          5. 30% or more marrow-bearing bone being irradiated. Other primary tumors within the last&#xD;
             5 years before study entry are not allowed, except for adequately controlled basal&#xD;
             cell carcinoma of the skin, or carcinoma in situ of the cervix.&#xD;
&#xD;
          6. Previous or current CNS metastases, carcinomatous meningitis, are not allowed. A CT or&#xD;
             MRI of the brain must be performed within 4 weeks prior to registration if the&#xD;
             presence of metastases at this site is suspected.&#xD;
&#xD;
          7. Evidence of clinically significant cardiovascular or pulmonary disease or any other&#xD;
             disease, metabolic or psychological dysfunction, physical examination finding, or&#xD;
             clinical laboratory finding giving reasonable suspicion of a disease or condition that&#xD;
             contraindicates the use of an investigational drug, or that may affect patient&#xD;
             compliance with study routines, or places the patient at high risk from treatment&#xD;
             related complications. (e.g lactose intolerance)&#xD;
&#xD;
          8. Previously received trifluridine/tipiracil&#xD;
&#xD;
          9. Since trifluridine/tipiracil contains lactose, patients with rare hereditary problems&#xD;
             of galactose intolerance, the Lapp lactase deficiency or glucose-galactose&#xD;
             malabsorption should not take this medicine&#xD;
&#xD;
         10. Diagnosis of any other malignancy prior to registration, except those that are not&#xD;
             believed to influence the patient's prognosis and do not require any further&#xD;
             treatment.&#xD;
&#xD;
         11. Other severe acute or chronic medical or psychiatric condition or laboratory&#xD;
             abnormality that may increase the risk associated with study participation or&#xD;
             investigational product administration or may interfere with the interpretation of&#xD;
             study results and, in the judgment of the investigator, would make the patient&#xD;
             inappropriate for entry into this study.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>A. Elise van Leeuwen-Stok, PhD</last_name>
    <role>Study Director</role>
    <affiliation>BOOG Study Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>M.M.E.M. Bos, MD PhD</last_name>
    <phone>+31-107034897</phone>
    <email>m.bos@erasmusmc.nl</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>R.M. Bijlsma, MD PhD</last_name>
    <phone>+31 88 75 555 55</phone>
    <email>R.M.Bijlsma@umcutrecht.nl</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Rijnstate</name>
      <address>
        <city>Arnhem</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>K Beelen</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Wilhelmina ziekenhuis</name>
      <address>
        <city>Assen</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>P. Nieboer</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Amphia Ziekenhuis</name>
      <address>
        <city>Breda</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>J. Heijns</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Reinier de Graaf Groep</name>
      <address>
        <city>Delft</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>M van Bekkum, MD</last_name>
    </contact>
    <investigator>
      <last_name>M van Bekkum, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Deventer ziekenhuis</name>
      <address>
        <city>Deventer</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>A Imholz, MD</last_name>
    </contact>
    <investigator>
      <last_name>A Imholz, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Catharina Ziekenhuis</name>
      <address>
        <city>Eindhoven</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>B.E.P.J. Vriens</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>MC Leeuwarden</name>
      <address>
        <city>Leeuwarden</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>H. De Graaf</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>MUMC</name>
      <address>
        <city>Maastricht</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>M de Boer, MD</last_name>
    </contact>
    <investigator>
      <last_name>M de Boer, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Erasmus MC</name>
      <address>
        <city>Rotterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>M Bos</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>UMC Utrecht</name>
      <address>
        <city>Utrecht</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>R.M.L. Bijlsma</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>July 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2020</study_first_posted>
  <last_update_submitted>February 21, 2023</last_update_submitted>
  <last_update_submitted_qc>February 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>TAS102</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Trifluridine</mesh_term>
  </intervention_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/NCT04489173
org study id: BOOG 2019-01
nct id: NCT04489173
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a multicenter phase 2 study evaluating the efficacy and safety of
      trifluridine/tipiracil in women with metastatic or locally advanced breast cancer not
      amenable to curative treatment by surgery or radiotherapy.
Multicenter phase 2 study evaluating the efficacy and safety of trifluridine/tipiracil in
      women with metastatic or locally advanced breast cancer not amenable to curative treatment by
      surgery or radiotherapy. This study will be conducted under the sponsorship of BOOG,
      Amsterdam, NL.

      Objectives:

      To evaluate the efficacy of trifluridine/tipiracil by determination of the percentage of
      patients being progression free at 8 weeks on trifluridine/tipiracil prescribed for
      ER-positive, HER2-negative advanced breast cancer patients previously treated with a taxane
      and capecitabine.

      Endpoints:

      Progression-free survival Response rate CR/PR at 16 weeks Adverse events Translational
      research on biological factors that may be of influence on the outcome of treatment QoL

      Main eligibility criteria:

      Metastatic Her2 negative, ER-positive breast cancer patients that progressed on, or after
      treatment with Capecitabine. Previous treatment with Taxanes is obligatory. Adequate
      hematology, liver and renal function tests.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Multicenter, single arm, phase 2 study evaluating the efficacy and safety of trifluridine/tipiracil in women with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy.
Study medication should be started within 3 days after completion of screening and continue until a study treatment discontinuation criterion is met.
Trifluridine/tipiracil will be administered orally BID on days 1 through 5, with the first dose administered in the morning of day 1 of each cycle and the last dose administered in the evening of day 5, followed by a recovery period from day 6 through day 7. Trifluridine/tipiracil will be administered orally BID on days 8 through 12, with the first dose administered in the morning of day 8 of each cycle and the last dose administered in the evening of day 12, followed by a recovery period from day 13 through day 28. Each cycle will be 28 days.
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free survival
time frame: 16 weeks
description: Response rate CR/PR
measure: Adverse events
time frame: every 4 weeks
description: CTCAE version 4.0
measure: QoL
time frame: 32 weeks
description: Quality of Life questionnaire EORTC QLQ-C30
arm group label: Treatment
arm group type: Experimental
description: Treatment with TAS102
intervention type: Drug
intervention name: trifluridine/tipiracil
description: Study medication should be started within 3 days after completion of screening and continue until a study treatment discontinuation criterion is met.
Trifluridine/tipiracil will be administered orally BID on days 1 through 5, with the first dose administered in the morning of day 1 of each cycle and the last dose administered in the evening of day 5, followed by a recovery period from day 6 through day 7. Trifluridine/tipiracil will be administered orally BID on days 8 through 12, with the first dose administered in the morning of day 8 of each cycle and the last dose administered in the evening of day 12, followed by a recovery period from day 13 through day 28. Each cycle will be 28 days.
arm group label: Treatment
other name: Lonsurf, TAS102
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: A. Elise van Leeuwen-Stok, PhD
role: Study Director
affiliation: BOOG Study Center
last name: M.M.E.M. Bos, MD PhD
phone: +31-107034897
email: m.bos@erasmusmc.nl
last name: R.M. Bijlsma, MD PhD
phone: +31 88 75 555 55
email: R.M.Bijlsma@umcutrecht.nl
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Netherlands
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Trifluridine