<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/NCT02983071</url>
  </required_header>
  <id_info>
    <org_study_id>G1T38-02</org_study_id>
    <secondary_id>2016-001485-29</secondary_id>
    <nct_id>NCT02983071</nct_id>
  </id_info>
  <brief_title>G1T38, a CDK 4/6 Inhibitor, in Combination With Fulvestrant in Hormone Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer</brief_title>
  <official_title>Phase 1/2 Safety, Pharmacokinetic, and Antitumor Activity Study of G1T38 in Combination With Fulvestrant in Patients With Hormone Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer After Endocrine Failure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>G1 Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>G1 Therapeutics, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a study to investigate the potential clinical benefit of G1T38 as an oral therapy in&#xD;
      combination with fulvestrant in patients with hormone receptor-positive, HER2-negative&#xD;
      metastatic breast cancer.&#xD;
&#xD;
      The study is an open-label design, consists of 2 parts: dose-finding portion (Part 1), and&#xD;
      expansion portion (Part 2). Both parts include 3 study phases: Screening Phase, Treatment&#xD;
      Phase, and Survival Follow-up Phase. The Treatment Phase begins on the day of first dose with&#xD;
      study treatment and completes at the Post-Treatment Visit. Approximately, 102 patients will&#xD;
      be enrolled in the study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>January 2017</start_date>
  <completion_date type="Anticipated">October 2023</completion_date>
  <primary_completion_date type="Anticipated">June 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>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dose Limiting Toxicity</measure>
    <time_frame>Week 1 Day 1-Week 5 Day 1</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Recommended Phase 2 dose</measure>
    <time_frame>14 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Recommended Phase 2 dose interval</measure>
    <time_frame>14 months</time_frame>
    <description>Twice-Daily or Once-Daily dosing</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Treatment Related Adverse Event, including Abnormal Laboratory Events</measure>
    <time_frame>36 months</time_frame>
    <description>All AEs, including clinical laboratory, vitals signs, physical examinations and ECGs will be analyzed in all patients receiving study drug from the signing of the informed consent until 30 days after the last dose of study medication up to 36 months</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tumor response based on RECIST, Version 1.1</measure>
    <time_frame>30 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Maximum Plasma Concentration (Cmax)</measure>
    <time_frame>Week 1 Day 1-Week 9 Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Area under Curve - plasma concentration (AUC)</measure>
    <time_frame>Week 1 Day 1-Week 9 Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Plasma: terminal half life (T1/2)</measure>
    <time_frame>Week 1 Day 1-Week 9 Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Plasma - Volume of distribution</measure>
    <time_frame>Week 1 Day 1-Week 9 Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>36 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>48 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">102</enrollment>
  <condition>Carcinoma, Ductal, Breast</condition>
  <condition>Breast Cancer</condition>
  <condition>Breast Neoplasm</condition>
  <arm_group>
    <arm_group_label>Once-Daily G1T38 Dosing</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>G1T38 (lerociclib) orally (once daily) in combination with fulvestrant.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Twice-Daily G1T38 Dosing</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>G1T38 (lerociclib) orally (twice daily) in combination with fulvestrant.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>G1T38</intervention_name>
    <arm_group_label>Once-Daily G1T38 Dosing</arm_group_label>
    <arm_group_label>Twice-Daily G1T38 Dosing</arm_group_label>
    <other_name>lerociclib</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fulvestrant</intervention_name>
    <arm_group_label>Once-Daily G1T38 Dosing</arm_group_label>
    <arm_group_label>Twice-Daily G1T38 Dosing</arm_group_label>
    <other_name>Faslodex</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Confirmed diagnosis of HR-positive, HER2-negative breast cancer, not amenable to&#xD;
             curative therapy&#xD;
&#xD;
          -  Pre- or perimenopausal women can be enrolled if amenable to be treated with goserelin&#xD;
&#xD;
          -  Patients must satisfy 1 of the following criteria for prior therapy:&#xD;
&#xD;
               -  Progressed during treatment or within 12 months of completion of adjuvant therapy&#xD;
                  with an aromatase inhibitor or tamoxifen&#xD;
&#xD;
               -  Progressed during treatment or within 2 months after the end of prior aromatase&#xD;
                  inhibitor therapy for advanced/metastatic breast cancer, or prior endocrine&#xD;
                  therapy for advanced/metastatic breast cancer&#xD;
&#xD;
               -  Received ≤ 2 chemotherapy regimens (Part 1) or ≤ 1 chemotherapy regimen (Part 2)&#xD;
                  for advanced/metastatic disease&#xD;
&#xD;
          -  For Part 1, evaluable or measurable disease (bone only disease eligible for Part 1&#xD;
             only)&#xD;
&#xD;
          -  For Part 2, measurable disease as defined by RECIST, Version 1.1&#xD;
&#xD;
          -  ECOG performance status 0 to 1&#xD;
&#xD;
          -  Adequate organ function&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  For Part 1, prior treatment with fulvestrant&#xD;
&#xD;
          -  For Part 2, prior treatment with any CDK inhibitor or fulvestrant&#xD;
&#xD;
          -  Active uncontrolled/symptomatic CNS metastases, carcinomatous meningitis, or&#xD;
             leptomeningeal disease&#xD;
&#xD;
          -  Chemotherapy within 21 days of first G1T38 dose&#xD;
&#xD;
          -  Investigational drug within 28 days of first G1T38 dose&#xD;
&#xD;
          -  Concurrent radiotherapy, radiotherapy within 14 days of first G1T38 dose, previous&#xD;
             radiotherapy to the target lesion sites, or prior radiotherapy to &gt; 25% of bone marrow&#xD;
&#xD;
          -  Prior hematopoietic stem cell or bone marrow transplantation&#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>Clinical Contact</last_name>
    <role>Study Director</role>
    <affiliation>G1 Therapeutics, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>MHAT for Womens Health - Nadezhda OOD</name>
      <address>
        <city>Sofia</city>
        <zip>1330</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Special Hospital For Active Treatment In Oncology</name>
      <address>
        <city>Sofia</city>
        <zip>1756</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ARENSIA Exploratory Medicine LLC</name>
      <address>
        <city>Tbilisi</city>
        <zip>0112</zip>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Institute of Oncology</name>
      <address>
        <city>Chisinau</city>
        <zip>2025</zip>
        <country>Moldova, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cambridge University</name>
      <address>
        <city>Cambridge</city>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University College London Hospital (UCLH)</name>
      <address>
        <city>London</city>
        <zip>NW1 2BU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute</name>
      <address>
        <city>London</city>
        <zip>W1G 6AD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Christie NHS Foundation</name>
      <address>
        <city>Manchester</city>
        <zip>M20 4BX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bulgaria</country>
    <country>Georgia</country>
    <country>Moldova, Republic of</country>
    <country>United Kingdom</country>
  </location_countries>
  <removed_countries>
    <country>Czech Republic</country>
    <country>Czechia</country>
    <country>Romania</country>
  </removed_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>November 29, 2016</study_first_submitted>
  <study_first_submitted_qc>December 1, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 6, 2016</study_first_posted>
  <last_update_submitted>February 14, 2023</last_update_submitted>
  <last_update_submitted_qc>February 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Breast Cancer</keyword>
  <keyword>CDK 4/6 Inhibitor</keyword>
  <keyword>HER2-Negative</keyword>
  <keyword>HR-Positive</keyword>
  <keyword>HR+</keyword>
  <keyword>HER2-</keyword>
  <keyword>HER2 -ve</keyword>
  <keyword>HER2 +ve</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Ductal</mesh_term>
    <mesh_term>Carcinoma, Ductal, Breast</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fulvestrant</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/NCT02983071
org study id: G1T38-02
secondary id: 2016-001485-29
nct id: NCT02983071
lead sponsor: 
has dmc: Yes
This is a study to investigate the potential clinical benefit of G1T38 as an oral therapy in
      combination with fulvestrant in patients with hormone receptor-positive, HER2-negative
      metastatic breast cancer.

      The study is an open-label design, consists of 2 parts: dose-finding portion (Part 1), and
      expansion portion (Part 2). Both parts include 3 study phases: Screening Phase, Treatment
      Phase, and Survival Follow-up Phase. The Treatment Phase begins on the day of first dose with
      study treatment and completes at the Post-Treatment Visit. Approximately, 102 patients will
      be enrolled in the study.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose Limiting Toxicity
time frame: Week 1 Day 1-Week 5 Day 1
measure: Recommended Phase 2 dose
time frame: 14 months
measure: Recommended Phase 2 dose interval
time frame: 14 months
description: Twice-Daily or Once-Daily dosing
measure: Number of Treatment Related Adverse Event, including Abnormal Laboratory Events
time frame: 36 months
description: All AEs, including clinical laboratory, vitals signs, physical examinations and ECGs will be analyzed in all patients receiving study drug from the signing of the informed consent until 30 days after the last dose of study medication up to 36 months
measure: Tumor response based on RECIST, Version 1.1
time frame: 30 months
measure: Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Maximum Plasma Concentration (Cmax)
time frame: Week 1 Day 1-Week 9 Day 1
measure: Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Area under Curve - plasma concentration (AUC)
time frame: Week 1 Day 1-Week 9 Day 1
measure: Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Plasma: terminal half life (T1/2)
time frame: Week 1 Day 1-Week 9 Day 1
measure: Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Plasma - Volume of distribution
time frame: Week 1 Day 1-Week 9 Day 1
measure: Progression free survival (PFS)
time frame: 36 months
measure: Overall survival (OS)
time frame: 48 months
arm group label: Once-Daily G1T38 Dosing
arm group type: Experimental
description: G1T38 (lerociclib) orally (once daily) in combination with fulvestrant.
arm group label: Twice-Daily G1T38 Dosing
arm group type: Experimental
description: G1T38 (lerociclib) orally (twice daily) in combination with fulvestrant.
intervention type: Drug
intervention name: G1T38
arm group label: Once-Daily G1T38 Dosing
arm group label: Twice-Daily G1T38 Dosing
other name: lerociclib
intervention type: Drug
intervention name: Fulvestrant
arm group label: Once-Daily G1T38 Dosing
arm group label: Twice-Daily G1T38 Dosing
other name: Faslodex
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Contact
role: Study Director
affiliation: G1 Therapeutics, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Bulgaria
country: Georgia
country: Moldova, Republic of
country: United Kingdom
country: Czech Republic
country: Czechia
country: Romania
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Carcinoma, Ductal
mesh term: Carcinoma, Ductal, Breast
mesh term: Fulvestrant