<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/NCT02232646</url>
  </required_header>
  <id_info>
    <org_study_id>BBI503-205a</org_study_id>
    <nct_id>NCT02232646</nct_id>
  </id_info>
  <brief_title>A Study of BBI503 in Adult Patients With Advanced Urologic Malignancies</brief_title>
  <official_title>A Phase II Clinical Study of BBI503 in Adult Patients With Advanced Urologic Malignancies</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 selected advanced urologic malignancies. The primary objective of this study is to&#xD;
      evaluate the disease control rate of patients with renal cell cancer and urothelial carcinoma&#xD;
      treated with BBI503.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Low feasibility&#xD;
  </why_stopped>
  <start_date>January 2017</start_date>
  <completion_date type="Actual">August 1, 2018</completion_date>
  <primary_completion_date type="Actual">August 1, 2018</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 BBI608 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">0</enrollment>
  <condition>Urologic Malignancies</condition>
  <condition>Renal Cell Carcinoma</condition>
  <condition>Urothelial Carcinoma</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&#xD;
&#xD;
          -  Histologically or cytologically confirmed renal cell cancer or urothelial carcinoma&#xD;
             that is metastatic, unresectable, or recurrent.&#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;
          -  Prothrombin time (PT) ≤ 16 seconds and partial thromboplastin time (PTT) ≤ 1.5 x ULN&#xD;
&#xD;
          -  Life expectancy ≥ 3 months&#xD;
&#xD;
          -  A patient with renal cell carcinoma (RCC) must be classified into clear-cell or&#xD;
             non-clear cell subtype, and must then meet the following criteria:&#xD;
&#xD;
               -  Patients with clear cell renal cancer must have received prior treatment with at&#xD;
                  least one line of standard systemic therapy which included treatment with a&#xD;
                  tyrosine kinase inhibitor; either alone or in combination. The patient must have&#xD;
                  had either progressive disease during treatment, or have had documented&#xD;
                  intolerance to first line tyrosine kinase inhibitor (TKI)-based therapy.&#xD;
&#xD;
               -  Patients with clear cell renal cancer who have received anti-cancer treatment&#xD;
                  beyond first-line TKI-based therapy may enroll.&#xD;
&#xD;
               -  Patients with clear cell renal cancer who have not received anti-cancer treatment&#xD;
                  beyond first-line TKI-based therapy may enroll only after discussing the&#xD;
                  potential risks and benefits of alternative treatment options, such as other&#xD;
                  currently available agents approved for treatment of patients with clear cell&#xD;
                  renal cancer.&#xD;
&#xD;
               -  Patients with non-clear cell RCC which is metastatic may enroll without having&#xD;
                  received prior treatment in the metastatic setting&#xD;
&#xD;
          -  A patient with urothelial carcinoma must also meet the following criteria:&#xD;
&#xD;
               -  Must have received at least one prior line of standard systemic cytotoxic therapy&#xD;
                  in the metastatic setting.&#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. 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>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>September 2, 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>Carcinoma</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Renal Cell</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/NCT02232646
org study id: BBI503-205a
nct id: NCT02232646
lead sponsor: 
has dmc: No
This is an open label, multi-center, Phase II study of BBI503 administered to adult patients
      with selected advanced urologic malignancies. The primary objective of this study is to
      evaluate the disease control rate of patients with renal cell cancer and urothelial carcinoma
      treated with BBI503.
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 BBI608 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
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Neoplasms
mesh term: Carcinoma, Renal Cell