<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/NCT02232620</url>
  </required_header>
  <id_info>
    <org_study_id>BBI503-205c</org_study_id>
    <nct_id>NCT02232620</nct_id>
  </id_info>
  <brief_title>A Study of BBI503 in Adult Patients With Advanced Gastrointestinal Stromal Tumors</brief_title>
  <official_title>A Phase II Clinical Study of BBI503 in Adult Patients With Advanced Gastrointestinal Stromal Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sumitomo Pharma Oncology, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sumitomo Pharma Oncology, Inc.</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>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open label, multi-center, phase II study of BBI503 administered to adult patients&#xD;
      with advanced gastrointestinal stromal tumor who have exhausted all currently approved&#xD;
      standard anti-cancer treatment options. BBI503 will be administered orally, daily, in&#xD;
      continuous 28-day cycles at a dose of 300 mg once daily. Cycles will be repeated until&#xD;
      patients are no longer clinically benefiting from therapy due to disease progression, adverse&#xD;
      events, or another discontinuation criterion.&#xD;
&#xD;
      Safety, tolerability and efficacy of BBI503 will be assessed for the duration of study&#xD;
      treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Low feasibility&#xD;
  </why_stopped>
  <start_date type="Actual">March 13, 2017</start_date>
  <completion_date type="Actual">July 25, 2017</completion_date>
  <primary_completion_date type="Actual">July 25, 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>Disease Control Rate (DCR)</measure>
    <time_frame>8 weeks</time_frame>
    <description>Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>8 weeks</time_frame>
    <description>Defined as the proportion of patients with a documented complete response and partial response (CR + PR) based on RECIST 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>24 months</time_frame>
    <description>Defined as the time from enrollment to the first objective documentation of disease progression or death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>24 months</time_frame>
    <description>Defined as the time from enrollment to death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients with Adverse Events</measure>
    <time_frame>24 months</time_frame>
    <description>All patients who have received at least one dose of BBI503 will be included in the safety analysis. The incidence of adverse events will be summarized by type of adverse event and severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamics (biomarkers) of BBI503 when tumor biopsy is possible</measure>
    <time_frame>baseline, 4 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">2</enrollment>
  <condition>Gastrointestinal Stromal Tumors</condition>
  <arm_group>
    <arm_group_label>BBI503</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BBI503</intervention_name>
    <description>BBI503 will be administered orally, daily, in continuous 28-day cycles at a dose of 300 mg once daily.</description>
    <arm_group_label>BBI503</arm_group_label>
    <other_name>Amcasertib</other_name>
    <other_name>BBI-503</other_name>
    <other_name>BB503</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed written informed consent must be obtained and documented according to&#xD;
             International Conference on Harmonisation (ICH) - Good Clinical Practice (GCP), the&#xD;
             local regulatory requirements, and permission to use private health information in&#xD;
             accordance with the Health Insurance Portability and Accountability Act (HIPPA) prior&#xD;
             to study-specific screening procedures&#xD;
&#xD;
          -  Histologically or cytologically confirmed gastrointestinal stromal tumor that is&#xD;
             metastatic, unresectable, or recurrent; and for which no currently approved, standard&#xD;
             anti-cancer treatment option is available.&#xD;
&#xD;
          -  ≥ 18 years of age&#xD;
&#xD;
          -  Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)&#xD;
             1.1&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1&#xD;
&#xD;
          -  Male or female patients of child-producing potential must agree to use contraception&#xD;
             or avoidance of pregnancy measures during the study and for 30 days after the last&#xD;
             BBI503 dose&#xD;
&#xD;
          -  Females of childbearing potential must have a negative serum pregnancy test&#xD;
&#xD;
          -  Alanine transaminase (ALT) ≤ 2.5 x the upper limit of normal (ULN), or ≤ 3.5 x ULN in&#xD;
             the presence of primary or metastatic hepatic lesions&#xD;
&#xD;
          -  Hemoglobin (Hgb) ≥ 10 g/dl&#xD;
&#xD;
          -  Total bilirubin ≤ 1.5 x ULN&#xD;
&#xD;
          -  Creatinine ≤ 1.5 x ULN or creatinine clearance &gt; 50 mL/min/1.73 m^2 for patients with&#xD;
             creatinine levels above institutional normal.&#xD;
&#xD;
          -  Absolute neutrophil count ≥ 1.5 x 10^9/L&#xD;
&#xD;
          -  Platelets ≥ 100 x 10^9/L&#xD;
&#xD;
          -  PT ≤ 16 seconds and PTT ≤ 1.5 x ULN&#xD;
&#xD;
          -  Life expectancy ≥ 3 months&#xD;
&#xD;
          -  A patient with gastrointestinal stromal tumor (GIST) must also meet the following&#xD;
             criteria:&#xD;
&#xD;
               -  Must have either positive immunostaining for the CD117-antigen, or contain a GIST&#xD;
                  associated KIT or PDGFR-α mutation.&#xD;
&#xD;
               -  Must have disease which is metastatic or locally advanced and unresectable&#xD;
&#xD;
               -  Must have received prior treatment with imatinib and sunitinib, and must have had&#xD;
                  disease progression during treatment with these agents, have had documented&#xD;
                  intolerance to these agents, or not be candidates for treatment with these&#xD;
                  agents.&#xD;
&#xD;
               -  Must have also failed or not be eligible for treatment with regorafenib.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents&#xD;
             within 7 days of first dose of BBI503. Patients may begin BBI503 on a date determined&#xD;
             by the investigator and medical monitor for the sponsor provided there is a minimum of&#xD;
             7 days since last receiving anti-cancer treatment, and that all prior&#xD;
             treatment-related AEs have resolved or have been deemed irreversible.&#xD;
&#xD;
          -  Major surgery within 4 weeks prior to first dose (requiring general anesthesia and/or&#xD;
             inpatient hospitalization for recovery).&#xD;
&#xD;
          -  Any known symptomatic or untreated brain metastases requiring increase of steroid dose&#xD;
             within 2 weeks prior to starting on study. Patients with treated brain metastases must&#xD;
             be stable for 4 weeks after completion of that treatment. Post-treatment image&#xD;
             documentation of stability is required within 4 months of starting on study. Patients&#xD;
             must have no clinical symptoms from brain metastases and must be either off steroids&#xD;
             or on a stable dose of steroids for at least 2 weeks prior to protocol enrollment.&#xD;
             Patients with known leptomeningeal metastases are excluded, even if treated.&#xD;
&#xD;
          -  Pregnant or breastfeeding&#xD;
&#xD;
          -  Significant gastrointestinal disorder(s), in the opinion of the Principal&#xD;
             Investigator, (e.g., Crohn's disease, ulcerative colitis, extensive gastric and small&#xD;
             intestine resection)&#xD;
&#xD;
          -  Unable or unwilling to swallow BBI503 capsules daily&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to ongoing or active&#xD;
             infection, clinically significant non-healing or healing wounds, symptomatic&#xD;
             congestive heart failure, unstable angina pectoris, cardiac arrhythmia, significant&#xD;
             pulmonary disease (shortness of breath at rest or mild exertion), uncontrolled&#xD;
             infection or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements (e.g. no reliable transportation).&#xD;
&#xD;
          -  Patients with a history of malignancies other than the tumor of interest except:&#xD;
             adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the&#xD;
             cervix, or other solid tumors curatively treated with no evidence of disease for &gt; 3&#xD;
             years.&#xD;
&#xD;
          -  Abnormal ECGs which are clinically significant such as QT prolongation - QTc &gt; 480&#xD;
             msec, clinically significant cardiac enlargement or hypertrophy, new bundle branch&#xD;
             block, or signs of active ischemia. Patients with evidence of prior infarction who are&#xD;
             New York Heart Association (NYHA) functional class II, III, or IV are excluded, as are&#xD;
             patients with marked arrhythmia such as Wolff Parkinson White pattern or complete&#xD;
             atrioventricular (AV) dissociation.&#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>Princess Margaret Cancer Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>September 3, 2014</study_first_submitted>
  <study_first_submitted_qc>September 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 5, 2014</study_first_posted>
  <last_update_submitted>April 4, 2022</last_update_submitted>
  <last_update_submitted_qc>April 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 5, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gastrointestinal Stromal Tumors</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/NCT02232620
org study id: BBI503-205c
nct id: NCT02232620
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: Yes
This is an open label, multi-center, phase II study of BBI503 administered to adult patients
      with advanced gastrointestinal stromal tumor who have exhausted all currently approved
      standard anti-cancer treatment options. BBI503 will be administered orally, daily, in
      continuous 28-day cycles at a dose of 300 mg once daily. Cycles will be repeated until
      patients are no longer clinically benefiting from therapy due to disease progression, adverse
      events, or another discontinuation criterion.

      Safety, tolerability and efficacy of BBI503 will be assessed for the duration of study
      treatment.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Disease Control Rate (DCR)
time frame: 8 weeks
description: Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.
measure: Objective Response Rate (ORR)
time frame: 8 weeks
description: Defined as the proportion of patients with a documented complete response and partial response (CR + PR) based on RECIST 1.1.
measure: Progression Free Survival (PFS)
time frame: 24 months
description: Defined as the time from enrollment to the first objective documentation of disease progression or death due to any cause.
measure: Overall Survival (OS)
time frame: 24 months
description: Defined as the time from enrollment to death due to any cause.
measure: Number of Patients with Adverse Events
time frame: 24 months
description: All patients who have received at least one dose of BBI503 will be included in the safety analysis. The incidence of adverse events will be summarized by type of adverse event and severity.
measure: Pharmacodynamics (biomarkers) of BBI503 when tumor biopsy is possible
time frame: baseline, 4 weeks
arm group label: BBI503
arm group type: Experimental
intervention type: Drug
intervention name: BBI503
description: BBI503 will be administered orally, daily, in continuous 28-day cycles at a dose of 300 mg once daily.
arm group label: BBI503
other name: Amcasertib
other name: BBI-503
other name: BB503
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Gastrointestinal Stromal Tumors