<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/NCT04499352</url>
  </required_header>
  <id_info>
    <org_study_id>1381-0011</org_study_id>
    <secondary_id>2019-004749-33</secondary_id>
    <nct_id>NCT04499352</nct_id>
  </id_info>
  <brief_title>A Study to Test BI 754091 Alone or in Combination With BI 836880 in People Who Have Advanced Anal Cancer</brief_title>
  <official_title>An Open Label, Randomized Phase II Study of BI 754091 Alone or in Combination With BI 836880 in Patients With Chemotherapy Resistant, Unresectable, Metastatic Squamous Cell Carcinoma of the Anal Canal</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this trial is to assess anti-tumour activity of BI 754091 as monotherapy and&#xD;
      of BI 754091 in combination with BI 836880 in patients with unresectable or metastatic&#xD;
      squamous cell carcinoma of the anal canal who progressed on or after chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Not due to safety reasons (sponsor decision).&#xD;
  </why_stopped>
  <start_date type="Actual">September 14, 2020</start_date>
  <completion_date type="Actual">October 19, 2020</completion_date>
  <primary_completion_date type="Actual">October 19, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective response (OR)</measure>
    <time_frame>up to 3 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of objective response (DoR)</measure>
    <time_frame>up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control (DC)</measure>
    <time_frame>up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events (AEs)</measure>
    <time_frame>up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Drug related AEs from the time of treatment initiation until the end of the Residual Effect Period (REP)</measure>
    <time_frame>up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Drug related AEs leading to dose reduction of BI 836880 and/or discontinuation of study treatment (i.e. both trial drugs)</measure>
    <time_frame>up to 3 years</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Anal Canal Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>treatment arm A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>treatment arm B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 754091</intervention_name>
    <description>BI 754091</description>
    <arm_group_label>treatment arm A</arm_group_label>
    <arm_group_label>treatment arm B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 836880</intervention_name>
    <description>BI 836880</description>
    <arm_group_label>treatment arm B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed and dated written Informed Consent Form (ICF) in accordance with ICH-GCP and&#xD;
             local legislation prior to admission to the trial.&#xD;
&#xD;
          2. Patients ≥18 years of age or over the legal age of consent in countries where that is&#xD;
             greater than 18 years at the time of signature of the ICF.&#xD;
&#xD;
          3. Patients must have histologically or cytologically documented surgically unresectable&#xD;
             locally-advanced or metastatic Squamous cell carcinoma of the anal canal (SCCA).&#xD;
&#xD;
          4. Patients with loco-regional anal cancer as initial diagnosis must have unresectable&#xD;
             progressive locally advanced or metastatic SCCA after failure of at least one line&#xD;
             (but not more than two lines) of previous systemic treatment unless ineligible for or&#xD;
             intolerant to this systemic therapy.&#xD;
&#xD;
             Patients with metastatic anal cancer as initial diagnosis (no prior treatment for&#xD;
             loco-regional cancer) must have failed one line of previous systemic treatment&#xD;
             (chemotherapy ± radiotherapy) for the metastatic anal cancer unless ineligible for or&#xD;
             intolerant to this systemic treatment. (Patients with metastatic anal cancer as&#xD;
             initial diagnosis who have received two or more lines of systemic treatment for the&#xD;
             metastatic anal cancer are not eligible for the study.)&#xD;
&#xD;
          5. All patients must have at least one measurable lesion according to RECIST v1.1&#xD;
             criteria.&#xD;
&#xD;
          6. Eastern Cooperative Oncology Group (ECOG) performance status score 0 to 1&#xD;
&#xD;
          7. All patients must be willing to undergo blood testing for human immunodeficiency virus&#xD;
             (HIV) presence in the blood if not tested within the past 6 months prior to signature&#xD;
             of ICF for this trial.&#xD;
&#xD;
             For patients confirmed as HIV positive, all of the following (a-d) applies:&#xD;
&#xD;
               1. CD4+ count ≥ 250 cells/μL&#xD;
&#xD;
               2. Undetectable viral load (local lab assessment)&#xD;
&#xD;
               3. Must be currently receiving Highly Active Antiretroviral Therapy&#xD;
&#xD;
               4. A HIV/Infectious Diseases specialist must be consulted or patient must be under&#xD;
                  the care of the HIV/Infectious Diseases specialist&#xD;
&#xD;
          8. Patients must be willing to allow programmed cell death ligand 1 (PD-L1) status&#xD;
             assessment by one of following options.&#xD;
&#xD;
             Preference is given to fresh tumour biopsy sample collection at baseline before&#xD;
             receiving first trial medication. In case a fresh tumour biopsy cannot be obtained&#xD;
             (e.g. inaccessible lesions or patient safety concern), archival tissue will be&#xD;
             requested. If neither is available any previous historical information regarding PD-L1&#xD;
             status should be collected via eCRF. Exceptions may be considered after consultation&#xD;
             with and approval by the Sponsor.&#xD;
&#xD;
          9. Male or female patients. Women of childbearing potential (WOCBP) and men able to&#xD;
             father a child must be ready and able to use highly effective methods of birth control&#xD;
             per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used&#xD;
             consistently and correctly, for the entire duration of the trial treatment intake and&#xD;
             for 6 months after the end of the trial treatment. A list of contraception methods&#xD;
             meeting these criteria is provided in the patient information.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Current or prior treatment with any systemic anti-cancer therapy or any&#xD;
             investigational product (or device) either within 28 days or less than 5 half-lives&#xD;
             (whichever is shorter) before start of trial treatment.&#xD;
&#xD;
          2. Major injuries and/or surgery or bone fracture within 4 weeks of start of treatment,&#xD;
             or planned surgical procedures during the trial period.&#xD;
&#xD;
          3. Significant cardiovascular/cerebrovascular diseases (i.e. uncontrolled hypertension,&#xD;
             unstable angina, history of infarction within past 6 months, congestive heart failure&#xD;
             &gt; New York Heart Association (NYHA) II).&#xD;
&#xD;
             Uncontrolled hypertension is defined as: blood pressure in rested and relaxed&#xD;
             condition ≥ 140 mmHg, systolic or ≥ 90 mmHg diastolic (with or without medication)&#xD;
&#xD;
          4. Known inherited predisposition to bleeding or to thrombosis in the opinion of the&#xD;
             investigator.&#xD;
&#xD;
          5. History of severe hemorrhagic or thromboembolic event in the past 12 months (excluding&#xD;
             central venous catheter thrombosis and peripheral deep vein thrombosis).&#xD;
&#xD;
          6. Patients who require full-dose anticoagulation (according to local guidelines). No&#xD;
             Vitamin K antagonist and other anticoagulation allowed; Low-Molecular-Weight-Heparin&#xD;
             (LMWH) and acetylsalicylic acid (ASA) allowed only for prevention not for curative&#xD;
             treatment.&#xD;
&#xD;
          7. Prior treatment with anti-PD-1, anti-PD-L1, or anti CTLA-4 treatment&#xD;
&#xD;
          8. Prior treatment with any antiangiogenic agent (e.g. bevacizumab, cediranib,&#xD;
             aflibercept, vandetanib, XL-184, sunitinib, etc.) Further exclusion criteria apply.&#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>Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <removed_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Spain</country>
  </removed_countries>
  <link>
    <url>https://www.mystudywindow.com</url>
    <description>Related Info</description>
  </link>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>August 3, 2020</study_first_submitted>
  <study_first_submitted_qc>August 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 5, 2020</study_first_posted>
  <last_update_submitted>November 12, 2021</last_update_submitted>
  <last_update_submitted_qc>November 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 15, 2021</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>Carcinoma, Squamous Cell</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions: 1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datasharing</ipd_description>
  </patient_data>
  <!-- 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/NCT04499352
org study id: 1381-0011
secondary id: 2019-004749-33
nct id: NCT04499352
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The objective of this trial is to assess anti-tumour activity of BI 754091 as monotherapy and
      of BI 754091 in combination with BI 836880 in patients with unresectable or metastatic
      squamous cell carcinoma of the anal canal who progressed on or after chemotherapy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective response (OR)
time frame: up to 3 years
measure: Duration of objective response (DoR)
time frame: up to 3 years
measure: Progression-free survival (PFS)
time frame: up to 3 years
measure: Overall survival (OS)
time frame: up to 3 years
measure: Disease control (DC)
time frame: up to 3 years
measure: Adverse events (AEs)
time frame: up to 3 years
measure: Drug related AEs from the time of treatment initiation until the end of the Residual Effect Period (REP)
time frame: up to 3 years
measure: Drug related AEs leading to dose reduction of BI 836880 and/or discontinuation of study treatment (i.e. both trial drugs)
time frame: up to 3 years
arm group label: treatment arm A
arm group type: Experimental
arm group label: treatment arm B
arm group type: Experimental
intervention type: Drug
intervention name: BI 754091
description: BI 754091
arm group label: treatment arm A
arm group label: treatment arm B
intervention type: Drug
intervention name: BI 836880
description: BI 836880
arm group label: treatment arm B
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Korea, Republic of
country: Australia
country: Belgium
country: Spain
url: https://www.mystudywindow.com
description: Related Info
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
sharing ipd: No
ipd description: Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions: 1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datasharing