<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/NCT02232633</url>
  </required_header>
  <id_info>
    <org_study_id>BBI503-205b</org_study_id>
    <secondary_id>BBI503-205HCC</secondary_id>
    <nct_id>NCT02232633</nct_id>
  </id_info>
  <brief_title>A Study of BBI503 in Adult Patients With Advanced Hepatobiliary Cancer</brief_title>
  <official_title>A Phase II Clinical Study of BBI503 in Adult Patients With Advanced Hepatobiliary Cancer</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open label, multi-center, phase II study of BBI503 administered to adult patients&#xD;
      with advanced hepatobiliary cancer who have exhausted all currently approved standard&#xD;
      anti-cancer treatment options. BBI503 will be administered orally, daily, in continuous&#xD;
      28-day cycles at a dose of 300 mg once daily. Cycles will be repeated until patients are no&#xD;
      longer clinically benefiting from therapy.&#xD;
&#xD;
      Safety, efficacy and tolerability of BBI503 will be assessed for the duration of study&#xD;
      treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>February 2015</start_date>
  <completion_date type="Actual">December 14, 2017</completion_date>
  <primary_completion_date type="Actual">December 14, 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>Pharmacodynamics (biomarkers) of BBI503 when tumor biopsy is possible</measure>
    <time_frame>baseline, 4 weeks</time_frame>
  </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>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <condition>Cholangiocarcinoma</condition>
  <arm_group>
    <arm_group_label>BBI503</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BBI503 will be administered orally, daily, in continuous 28-day cycles at a dose of 300 mg once daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BBI503</intervention_name>
    <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 hepatocellular carcinoma or&#xD;
             cholangiocarcinoma, that is metastatic, unresectable, or recurrent; and for which no&#xD;
             currently approved, standard anti-cancer treatment option is available. Patients must&#xD;
             have received standard of care treatment prior to enrollment.&#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;
          -  Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤ 5.0x the upper limit of&#xD;
             normal (ULN)&#xD;
&#xD;
          -  Hemoglobin &gt; 8.0 g/dL&#xD;
&#xD;
          -  Total bilirubin ≤ 2.5 x ULN&#xD;
&#xD;
          -  Creatinine ≤ 1.5 x ULN or creatinine clearance &gt; 50 mL/min according to the&#xD;
             Cockcroft-Gault estimation.&#xD;
&#xD;
          -  Absolute neutrophil count ≥ 1.5 x 10^9/L&#xD;
&#xD;
          -  Platelets ≥ 60 x 10^9/L&#xD;
&#xD;
          -  Life expectancy ≥ 3 months&#xD;
&#xD;
          -  A patient with hepatocellular carcinoma (HCC) which has arisen out of any medical&#xD;
             context must also meet the following criteria:&#xD;
&#xD;
          -  Must not be a candidate for potentially curative resection&#xD;
&#xD;
          -  Must be Child-Pugh class A or B7 (i.e., in order to be eligible, the total Child-Pugh&#xD;
             score for a patient must be ≤ 7)&#xD;
&#xD;
          -  Must have received prior treatment with sorafenib; and have had either disease&#xD;
             progression during treatment or have had documented intolerance to sorafenib such that&#xD;
             further treatment with sorafenib is not possible.&#xD;
&#xD;
          -  Patients with uncontrolled massive ascites or presence of hepatic encephalopathy&#xD;
             within four (4) weeks of first dose are excluded&#xD;
&#xD;
          -  A patient with confirmed cholangiocarcinoma of any type must also meet the following&#xD;
             criteria:&#xD;
&#xD;
          -  Must have disease which is not amenable to surgical, radiation, or combined modality&#xD;
             therapy with curative intent&#xD;
&#xD;
          -  Must have received prior treatment with gemcitabine, either alone or in combination&#xD;
             with a platinum agent. Patients who are not eligible for gemcitabine must have&#xD;
             received an alternate first-line systemic chemotherapy regimen&#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 adverse events (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. Patients must have no&#xD;
             clinical symptoms from brain metastases and must be either off steroids or on a stable&#xD;
             dose of steroids for at least 2 weeks prior to protocol enrollment. Patients with&#xD;
             known leptomeningeal metastases are excluded, even if treated.&#xD;
&#xD;
          -  Pregnant or breastfeeding&#xD;
&#xD;
          -  Significant gastrointestinal disorder(s), in the opinion of the treating investigator,&#xD;
             (e.g., Crohn's disease, ulcerative colitis, extensive gastric and small intestine&#xD;
             resection); such that absorption of oral medications may be impaired.&#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;
          -  Subjects with history of another primary cancer, with the exception of: a) curatively&#xD;
             resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ;&#xD;
             or c) other primary solid tumor with no known active disease present in the opinion of&#xD;
             the investigator will not affect patient outcome in the setting of current&#xD;
             hepatobiliary malignancy.&#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>University of Calgary</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 4N2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ottawa Hospital Cancer Centre</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1H 8L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Margaret Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <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 3, 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>Cholangiocarcinoma</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/NCT02232633
org study id: BBI503-205b
secondary id: BBI503-205HCC
nct id: NCT02232633
lead sponsor: 
has dmc: No
This is an open label, multi-center, phase II study of BBI503 administered to adult patients
      with advanced hepatobiliary cancer 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.

      Safety, efficacy and tolerability 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: Pharmacodynamics (biomarkers) of BBI503 when tumor biopsy is possible
time frame: baseline, 4 weeks
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.
arm group label: BBI503
arm group type: Experimental
description: BBI503 will be administered orally, daily, in continuous 28-day cycles at a dose of 300 mg once daily
intervention type: Drug
intervention name: BBI503
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: 
facility: 
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Cholangiocarcinoma