<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/NCT03780517</url>
  </required_header>
  <id_info>
    <org_study_id>BOS172738-01</org_study_id>
    <secondary_id>2018-002612-27</secondary_id>
    <nct_id>NCT03780517</nct_id>
  </id_info>
  <brief_title>Safety, Efficacy, and Tolerability of BOS172738 in Patients With Advanced Rearranged During Transfection (RET) Gene-Altered Tumors</brief_title>
  <official_title>A Phase 1 Study of BOS172738 in Patients With Advanced Solid Tumors With RET Gene Alterations Including Non-Small Cell Lung Cancer (NSCLC) and Medullary Thyroid Cancer (MTC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boston Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boston Pharmaceuticals</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</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>
      This study will be conducted to assess the safety and tolerability of BOS172738 when&#xD;
      administered to patients with advanced solid tumors with rearranged during transfection (RET)&#xD;
      gene alterations and also to establish the maximum tolerated dose (MTD) and/or recommended&#xD;
      phase 2 dose (RP2D) of BOS172738.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 12, 2018</start_date>
  <completion_date type="Anticipated">August 2024</completion_date>
  <primary_completion_date type="Anticipated">March 2024</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>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with any treatment-emergent (TE) serious adverse event (SAE)</measure>
    <time_frame>a minimum of approximately 3 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with any non-serious TEAE</measure>
    <time_frame>a minimum of approximately 3 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with grade 3, grade 4, or grade 5 TEAEs</measure>
    <time_frame>a minimum of approximately 3 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with any related TEAE</measure>
    <time_frame>a minimum of approximately 3 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with any TEAE leading to study drug discontinuation</measure>
    <time_frame>a minimum of approximately 3 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum tolerated dose (MTD) of BOS172738</measure>
    <time_frame>throughout Cycle 1 (each cycle is 28 days)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Recommended phase 2 dose (RP2D) of BOS172738</measure>
    <time_frame>28-day cycles in Part A (minimum of one dose of BOS172738 received)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>a minimum of approximately 3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Disease Control Rate (ODCR)</measure>
    <time_frame>a minimum of approximately 3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS)</measure>
    <time_frame>a minimum of approximately 3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DoR)</measure>
    <time_frame>a minimum of approximately 3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Response (TTR)</measure>
    <time_frame>a minimum of approximately 3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Complete Response (DoCR)</measure>
    <time_frame>a minimum of approximately 3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Plasma concentration of BOS172738</measure>
    <time_frame>Pre-dose on Days 1, 2, 15, and 16 of Cycle 1; Day 1 of Cycles 2, 3, and 4. 15 minutes (min); 30 min; 1, 3, 6, 8, 10, and 12 hours after the BOS1722722 dose on Days 1 and 15 of Cycle 1 (each cycle is 28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Plasma concentration of BOS172738</measure>
    <time_frame>Pre-dose on Day 1 of Cycles 2, 3, and 4 (each cycle is 28 days)</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">117</enrollment>
  <condition>Advanced Nonhaematologic Malignancies</condition>
  <arm_group>
    <arm_group_label>BOS172738</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In Part A (dose escalation), participants with advanced solid tumors with rearranged during transfection (RET) gene alterations will receive oral BOS172738 at a starting dose of 10 milligrams (mg) once daily in each 28-day cycle. In Part B (dose expansion), participants with RET gene-fusion non-small cell lung cancer (NSCLC), with RET gene-mutant medullary thyroid cancer (MTC), and with RET gene-altered advanced tumors or NSCLC/MTC with prior specific RET gene-targeted therapy will be enrolled in Cohorts 1, 2, and 3, respectively, and will receive oral BOS172738 once daily in each 28-day cycle at the recommended Phase 2 dose (RP2D) established in Part A.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BOS172738</intervention_name>
    <description>Oral capsules</description>
    <arm_group_label>BOS172738</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Participants are eligible to be included in the study only if all of the following criteria&#xD;
        apply:&#xD;
&#xD;
          -  Male or female participants must be ≥ 18 years, at the time of signing the informed&#xD;
             consent&#xD;
&#xD;
          -  Diagnosis of advanced solid tumor with a documented rearranged during transfection&#xD;
             (RET) gene altered malignancy as determined locally by a DNA based assay of tumor&#xD;
             tissue and/or blood&#xD;
&#xD;
          -  Participants must have no alternative approved therapy.&#xD;
&#xD;
          -  For participants in Part B expansion cohort only: documented local diagnosis of either&#xD;
             1) advanced RET gene fusion non-small cell lung cancer (NSCLC); 2) advanced RET gene&#xD;
             mutant medullary thyroid cancer (MTC); or 3) other RET gene altered advanced tumors or&#xD;
             NSCLC/MTC with prior specific RET gene targeted therapy&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1&#xD;
&#xD;
          -  Negative pregnancy test for females of child bearing potential; must be surgically&#xD;
             sterile, postmenopausal, or willing and able to be compliant with a contraceptive&#xD;
             regimen&#xD;
&#xD;
          -  Contraceptive use by men or women should be consistent with local regulations.&#xD;
&#xD;
          -  Capable of giving signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Participants are excluded from the study if any of the following criteria apply:&#xD;
&#xD;
          -  Inability to take oral medications or gastrointestinal (GI) conditions that can&#xD;
             interfere with the swallowing or absorption of study medication&#xD;
&#xD;
          -  Uncontrolled or severe concurrent medical condition&#xD;
&#xD;
          -  History of upper GI bleeding, ulceration, or perforation within 12 months prior to the&#xD;
             first dose of study drug&#xD;
&#xD;
          -  Known history of stroke or cerebrovascular accident within 6 months prior to the first&#xD;
             dose of study drug&#xD;
&#xD;
          -  Participants with known infection with human immunodeficiency virus (HIV) or Acquired&#xD;
             Immune Deficiency Syndrome (AIDS) (testing not required)&#xD;
&#xD;
          -  Participants who are hepatitis B surface antigen positive or participants who are&#xD;
             hepatitis C antibody positive (Participants who have been successfully treated for&#xD;
             hepatitis C virus [HCV] are eligible if an undetectable HCV viral load at least 6&#xD;
             months after completion of treatment can be demonstrated.)&#xD;
&#xD;
          -  Any evidence of serious active infections&#xD;
&#xD;
          -  Uncontrolled or severe cardiovascular disease&#xD;
&#xD;
          -  Uncontrolled intercurrent illness or psychiatric illness/social situations that would&#xD;
             limit compliance with study requirements&#xD;
&#xD;
          -  Participants with a prior or concurrent malignancy other than the malignancies under&#xD;
             study&#xD;
&#xD;
          -  Ongoing cancer directed therapy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Fox Chase Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Jules Bordet</name>
      <address>
        <city>Bruxelles</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven</name>
      <address>
        <city>Leuven</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Bergonié</name>
      <address>
        <city>Bordeaux</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Léon Bérard</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Pitié-Salpêtrière</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prince of Wales Hospital</name>
      <address>
        <city>Hong Kong</city>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chungbuk National University Hospital</name>
      <address>
        <city>Cheongju-si</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Bundang Hospital</name>
      <address>
        <city>Gyeonggi-do</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Korea University Anam Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Severance Hospital, Yonsei University College of Medicine</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen de la Victoria</name>
      <address>
        <city>Málaga</city>
        <state>Andalucia</state>
        <zip>29010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Germans Trias i Pujol</name>
      <address>
        <city>Badalona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Oncológico Dr. Rosell, S.L.</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Start Madrid - Ciocc</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>START MADRID-FJD, Hospital Fundación Jiménez Díaz</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taichung Veterans General Hospital</name>
      <address>
        <city>Taichung</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>France</country>
    <country>Hong Kong</country>
    <country>Korea, Republic of</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>December 12, 2018</study_first_submitted>
  <study_first_submitted_qc>December 17, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>May 1, 2023</last_update_submitted>
  <last_update_submitted_qc>May 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>BOS172738</keyword>
  <keyword>RET gene</keyword>
  <keyword>Medullary Thyroid Cancer</keyword>
  <keyword>Non-Small Cell Lung Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_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/NCT03780517
org study id: BOS172738-01
secondary id: 2018-002612-27
nct id: NCT03780517
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This study will be conducted to assess the safety and tolerability of BOS172738 when
      administered to patients with advanced solid tumors with rearranged during transfection (RET)
      gene alterations and also to establish the maximum tolerated dose (MTD) and/or recommended
      phase 2 dose (RP2D) of BOS172738.
allocation: N/A
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with any treatment-emergent (TE) serious adverse event (SAE)
time frame: a minimum of approximately 3 months
measure: Number of participants with any non-serious TEAE
time frame: a minimum of approximately 3 months
measure: Number of participants with grade 3, grade 4, or grade 5 TEAEs
time frame: a minimum of approximately 3 months
measure: Number of participants with any related TEAE
time frame: a minimum of approximately 3 months
measure: Number of participants with any TEAE leading to study drug discontinuation
time frame: a minimum of approximately 3 months
measure: Maximum tolerated dose (MTD) of BOS172738
time frame: throughout Cycle 1 (each cycle is 28 days)
measure: Recommended phase 2 dose (RP2D) of BOS172738
time frame: 28-day cycles in Part A (minimum of one dose of BOS172738 received)
measure: Objective Response Rate (ORR)
time frame: a minimum of approximately 3 months
measure: Objective Disease Control Rate (ODCR)
time frame: a minimum of approximately 3 months
measure: Progression-Free Survival (PFS)
time frame: a minimum of approximately 3 months
measure: Duration of Response (DoR)
time frame: a minimum of approximately 3 months
measure: Time to Response (TTR)
time frame: a minimum of approximately 3 months
measure: Duration of Complete Response (DoCR)
time frame: a minimum of approximately 3 months
measure: Part A: Plasma concentration of BOS172738
time frame: Pre-dose on Days 1, 2, 15, and 16 of Cycle 1; Day 1 of Cycles 2, 3, and 4. 15 minutes (min); 30 min; 1, 3, 6, 8, 10, and 12 hours after the BOS1722722 dose on Days 1 and 15 of Cycle 1 (each cycle is 28 days)
measure: Part B: Plasma concentration of BOS172738
time frame: Pre-dose on Day 1 of Cycles 2, 3, and 4 (each cycle is 28 days)
arm group label: BOS172738
arm group type: Experimental
description: In Part A (dose escalation), participants with advanced solid tumors with rearranged during transfection (RET) gene alterations will receive oral BOS172738 at a starting dose of 10 milligrams (mg) once daily in each 28-day cycle. In Part B (dose expansion), participants with RET gene-fusion non-small cell lung cancer (NSCLC), with RET gene-mutant medullary thyroid cancer (MTC), and with RET gene-altered advanced tumors or NSCLC/MTC with prior specific RET gene-targeted therapy will be enrolled in Cohorts 1, 2, and 3, respectively, and will receive oral BOS172738 once daily in each 28-day cycle at the recommended Phase 2 dose (RP2D) established in Part A.
intervention type: Drug
intervention name: BOS172738
description: Oral capsules
arm group label: BOS172738
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
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country: Belgium
country: France
country: Hong Kong
country: Korea, Republic of
country: Spain
country: Taiwan
country: United States
responsible party type: Sponsor
mesh term: Neoplasms