<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/NCT03240016</url>
  </required_header>
  <id_info>
    <org_study_id>UMCC 2017.077</org_study_id>
    <secondary_id>HUM00135166</secondary_id>
    <nct_id>NCT03240016</nct_id>
  </id_info>
  <brief_title>Abraxane With Anti-PD1/PDL1 in Patients With Advanced Urothelial Cancer</brief_title>
  <acronym>ABLE</acronym>
  <official_title>ABLE: Phase II, Single Arm, Two-stage Study of Abraxane With Anti-PD1/PDL1 in Patients With Advanced Urothelial Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan Rogel Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Michigan Rogel Cancer Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <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 is a phase 2, single arm, two-stage study of abraxane with an anti-PD1/PDL1&#xD;
      (pembrolizumab) in cisplatin-ineligible patients with advanced urothelial cancer.&#xD;
&#xD;
      Each cycle last 21-days. All subjects will receive pembrolizumab via IV on day 1, and&#xD;
      abraxane via IV on Day 1 and Day 8 of each cycle. Subjects may continue to receive the study&#xD;
      regimen until they experience disease progression or unacceptable toxicity.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 8, 2018</start_date>
  <completion_date type="Actual">June 23, 2023</completion_date>
  <primary_completion_date type="Actual">June 23, 2023</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>Percentage of patients that respond to treatment</measure>
    <time_frame>24 months post treatment</time_frame>
    <description>The Overall Response Rate (ORR) will be the percentage of patients that achieve either complete response (CR) or partial response (PR).&#xD;
CR is defined as the disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions.&#xD;
PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. There can be no appearance of new lesions.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of response</measure>
    <time_frame>24 months post treatment</time_frame>
    <description>The duration of response (DOR) is measured from the time that response (PR or CR) criteria are met until the first date that recurrent or progressive disease is objectively documented.&#xD;
CR is defined as the disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions.&#xD;
PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. There can be no appearance of new lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival time</measure>
    <time_frame>24 months post treatment</time_frame>
    <description>Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death.&#xD;
Progressive disease (PD) is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median number of patients alive at 12 and 24 months</measure>
    <time_frame>12 and 24 months post treatment</time_frame>
    <description>Overall survival will be documented as the median number of patients alive at 12 and 24 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median duration of therapy</measure>
    <time_frame>24 months post treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of patients that completely respond to treatment</measure>
    <time_frame>24 months post treatment</time_frame>
    <description>The percentage of patients that achieve complete response to treatment. Complete response is defined as the disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Urothelial Carcinoma</condition>
  <arm_group>
    <arm_group_label>Pembrolizumab and Abraxane</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pembrolizumab 200mg IV D1 Abraxane 100mg/m^2 IV D1 and D8 21 Day Cycles</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>200mg IV D1</description>
    <arm_group_label>Pembrolizumab and Abraxane</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Abraxane</intervention_name>
    <description>100mg/m^2 D1 and D8</description>
    <arm_group_label>Pembrolizumab and Abraxane</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with recurrent unresectable locally advanced or metastatic urothelial&#xD;
             carcinoma (aka transitional cell carcinoma).&#xD;
&#xD;
          -  Patients may be either cisplatin-ineligible or platinum-refractory.&#xD;
&#xD;
          -  Histological or cytologically proven urothelial carcinoma.&#xD;
&#xD;
          -  Have measurable disease based on RECIST 1.1&#xD;
&#xD;
          -  Has urothelial cancer that is not suitable for local therapy administered with&#xD;
             curative intent if not already administered.&#xD;
&#xD;
          -  Must have recovered (i.e., AE &lt;= Grade 1 or stable) from AEs due to a previously&#xD;
             administered agent.&#xD;
&#xD;
          -  ECOG Performance Status of 0, 1 or 2. (Eastern Cooperative Oncology Group Performance&#xD;
             Status: an attempt to quantify cancer patients' general well-being and activities of&#xD;
             daily life. The score ranges from 0 to 5 where 0 is asymptomatic and 5 is death.)&#xD;
&#xD;
          -  Prior neoadjuvant or adjuvant systemic therapy or local intravesical chemotherapy or&#xD;
             immunotherapy is permitted.&#xD;
&#xD;
          -  Adequate organ and marrow function&#xD;
&#xD;
          -  Women of child-bearing potential must either commit to true abstinence or agree to&#xD;
             use, and be able to comply with, effective contraception without interruption, 28 days&#xD;
             prior to starting IP therapy, and while on study medication or for a longer period if&#xD;
             required by local regulations following the last dose of IP; and have a negative serum&#xD;
             pregnancy test result at screening&#xD;
&#xD;
          -  Male subjects must practice true abstinence or agree to use a condom during sexual&#xD;
             contact with a pregnant female or a female of childbearing potential while&#xD;
             participating in the study, during dose interruptions and for 6 months following drug&#xD;
             discontinuation, even if he has undergone a successful vasectomy.&#xD;
&#xD;
          -  Patients must have &lt; Grade 2 pre-existing peripheral neuropathy&#xD;
&#xD;
          -  Be ≥18 years of age as of date of signing informed consent&#xD;
&#xD;
          -  Voluntarily agree to participate by providing written informed consent/assent for the&#xD;
             trial&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior exposure to immune-mediated therapy&#xD;
&#xD;
          -  History of allogenic organ transplantation that requires ongoing use of&#xD;
             immunosuppressive agents is NOT permitted&#xD;
&#xD;
          -  Active or prior documented autoimmune or inflammatory disorders are NOT permitted&#xD;
&#xD;
          -  Current or prior use of immunosuppressive medication(s) within 14 days before study&#xD;
             treatment is NOT permitted.&#xD;
&#xD;
          -  Brain metastases or spinal cord compression are NOT permitted unless they have been&#xD;
             treated with the patient's condition being stable clinically and radiologically for 28&#xD;
             calendar days and off steroids for at least 14 days prior to the start of study&#xD;
             treatment.&#xD;
&#xD;
          -  Active infection including tuberculosis, hepatitis B, hepatitis C, or human&#xD;
             immunodeficiency virus (HIV) is NOT permitted.&#xD;
&#xD;
          -  Receipt of live attenuated vaccine within 30 days prior to the first study treatment&#xD;
             is NOT permitted.&#xD;
&#xD;
          -  Is currently participating and receiving study therapy or has participated in a study&#xD;
             of an investigational agent and received study therapy or used an investigation device&#xD;
             within 28 calendar days of the first dose of treatment.&#xD;
&#xD;
          -  CTCAE Grade &gt; 1 peripheral neuropathy is NOT permitted&#xD;
&#xD;
          -  If subjects received major surgery they must have recovered adequately from the&#xD;
             toxicity and/or complications from the intervention prior to starting trial therapy&#xD;
&#xD;
          -  Has a known additional malignancy that is progressing or requires active treatment&#xD;
&#xD;
          -  Has a history of severe hypersensitivity reaction to nab-paclitaxel or anti-PD1/PDL1&#xD;
&#xD;
          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality&#xD;
             that might confound the results of the trial, interfere with the subject's&#xD;
             participation for the full duration of the trial, or is not in the best interest of&#xD;
             the subject to participate, in the opinion of the treating investigator&#xD;
&#xD;
          -  Has known psychiatric or substance abuse disorders that would interfere with&#xD;
             cooperation with the requirements of the trial&#xD;
&#xD;
          -  Pregnancies:&#xD;
&#xD;
               1. Females: nab-paclitaxel can cause harm to an unborn child if given to a pregnant&#xD;
                  woman. Females may not take part in this study if pregnant or breast-feeding for&#xD;
                  6 months after last dose of study drug.&#xD;
&#xD;
               2. Males: Male subjects should avoid fathering a child while receiving study&#xD;
                  medication and for 6 months after the last dose of study medication. Males must&#xD;
                  agree to complete abstinence from heterosexual contact or use a condom during&#xD;
                  sexual contact with a female of child bearing potential while receiving study&#xD;
                  medication and within 6 months after last dose of study medication.&#xD;
&#xD;
               3. Subjects (both males and female) should practice effective contraception during&#xD;
                  study and for 6 months after the last dose of study medication (Section 3.1.8 i,&#xD;
                  ii).&#xD;
&#xD;
          -  Patients with biliary obstruction or biliary stent are excluded.&#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>Ajjai Alva, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan Rogel Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Michigan Comprehensive Cancer Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 27, 2017</study_first_submitted>
  <study_first_submitted_qc>August 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2017</study_first_posted>
  <last_update_submitted>August 30, 2023</last_update_submitted>
  <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 31, 2023</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, Transitional Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
    <mesh_term>Albumin-Bound Paclitaxel</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/NCT03240016
org study id: UMCC 2017.077
secondary id: HUM00135166
nct id: NCT03240016
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This is a phase 2, single arm, two-stage study of abraxane with an anti-PD1/PDL1
      (pembrolizumab) in cisplatin-ineligible patients with advanced urothelial cancer.

      Each cycle last 21-days. All subjects will receive pembrolizumab via IV on day 1, and
      abraxane via IV on Day 1 and Day 8 of each cycle. Subjects may continue to receive the study
      regimen until they experience disease progression or unacceptable toxicity.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of patients that respond to treatment
time frame: 24 months post treatment
description: The Overall Response Rate (ORR) will be the percentage of patients that achieve either complete response (CR) or partial response (PR).
CR is defined as the disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions.
PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. There can be no appearance of new lesions.
measure: Duration of response
time frame: 24 months post treatment
description: The duration of response (DOR) is measured from the time that response (PR or CR) criteria are met until the first date that recurrent or progressive disease is objectively documented.
CR is defined as the disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions.
PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. There can be no appearance of new lesions.
measure: Progression free survival time
time frame: 24 months post treatment
description: Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death.
Progressive disease (PD) is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions.
measure: Median number of patients alive at 12 and 24 months
time frame: 12 and 24 months post treatment
description: Overall survival will be documented as the median number of patients alive at 12 and 24 months.
measure: Median duration of therapy
time frame: 24 months post treatment
measure: Percentage of patients that completely respond to treatment
time frame: 24 months post treatment
description: The percentage of patients that achieve complete response to treatment. Complete response is defined as the disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions.
arm group label: Pembrolizumab and Abraxane
arm group type: Experimental
description: Pembrolizumab 200mg IV D1 Abraxane 100mg/m^2 IV D1 and D8 21 Day Cycles
intervention type: Drug
intervention name: Pembrolizumab
description: 200mg IV D1
arm group label: Pembrolizumab and Abraxane
intervention type: Drug
intervention name: Abraxane
description: 100mg/m^2 D1 and D8
arm group label: Pembrolizumab and Abraxane
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ajjai Alva, M.D.
role: Principal Investigator
affiliation: University of Michigan Rogel Cancer Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma, Transitional Cell
mesh term: Pembrolizumab
mesh term: Albumin-Bound Paclitaxel