<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/NCT04407247</url>
  </required_header>
  <id_info>
    <org_study_id>2019-0276</org_study_id>
    <secondary_id>NCI-2019-04986</secondary_id>
    <secondary_id>2019-0276</secondary_id>
    <nct_id>NCT04407247</nct_id>
  </id_info>
  <brief_title>Infliximab or Vedolizumab in Treating Immune Checkpoint Inhibitor-Related Colitis in Patients With Genitourinary Cancer or Melanoma</brief_title>
  <official_title>Treatment of Immune Checkpoint Inhibitor-Related Colitis With Infliximab or Vedolizumab: A Randomized Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I/II trial studies the side effects of infliximab and vedolizumab and to see how&#xD;
      well they work in treating inflammation of the colon (colitis) caused by immune checkpoint&#xD;
      inhibitor therapy in patients with cancer of the genital and urinary organs (genitourinary)&#xD;
      or melanoma. Monoclonal antibodies, such as infliximab or vedolizumab, may help to treat&#xD;
      immunotherapy induced colitis/diarrhea. This study may help to identify the optimal treatment&#xD;
      strategy for immune checkpoint inhibitor-related colitis in patients with genitourinary&#xD;
      cancer or melanoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To compare the efficacy of infliximab and vedolizumab for clinical remission/response of&#xD;
      immune-related diarrhea and/or colitis.&#xD;
&#xD;
      II. To assess the safety and tolerability of the treatment for immune-mediated diarrhea&#xD;
      and/or colitis.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To assess the efficacy of infliximab and vedolizumab for clinical remission/response of&#xD;
      IMC at 4 weeks.&#xD;
&#xD;
      II. To assess the success of corticosteroid tapering. III. To measure the recurrence rate&#xD;
      after corticosteroid taper.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. To assess the efficacy of infliximab and vedolizumab to achieve endoscopic remission of&#xD;
      immune-related diarrhea and/or colitis.&#xD;
&#xD;
      II. To assess the efficacy of infliximab and vedolizumab to achieve histological remission of&#xD;
      immune-related diarrhea and/or colitis.&#xD;
&#xD;
      III. To assess the time duration to achieve the clinical remission/response. IV. To assess&#xD;
      the long term outcome of cancer. V. To assess immunological, molecular and microbiome changes&#xD;
      in tissue/blood/stool.&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 2 arms.&#xD;
&#xD;
      ARM I: Patients receive infliximab intravenously (IV) over 1 hour once at week 0, 2, 6 for a&#xD;
      total of 3 doses in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      ARM II: Patients receive vedolizumab IV over 1 hour once at week 0, 2, 6 for a total of 3&#xD;
      doses in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      Patients are followed up weekly for 1 month and then at 2 and 3 months after the treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 9, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <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>Clinical remission/response rate of immune-mediated colitis (IMC)</measure>
    <time_frame>At 2 weeks after initiation of infliximab or vedolizumab with corticosteroid taper</time_frame>
    <description>The difference of the remission rate between standard of care (infliximab + corticosteroid) and the treatment with vedolizumab + corticosteroid will be calculated along with the 95% confidence interval.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Treatment-related adverse events</measure>
    <time_frame>Within 3 months after initiation of infliximab or vedolizumab</time_frame>
    <description>Will follow standard reporting guidelines for adverse events. Safety data will be summarized by category, severity and frequency.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical remission/response rate of IMC</measure>
    <time_frame>At 4 weeks after initiation of infliximab or vedolizumab with corticosteroid taper</time_frame>
    <description>Will be estimated and compared between the two treatment arms using chi-square test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complete weaning of corticosteroid</measure>
    <time_frame>Within 4 weeks after infliximab or vedolizumab initiation without rebound of IMC</time_frame>
    <description>Will be estimated and compared between the two treatment arms using chi-square test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recurrent immune-related diarrhea/colitis</measure>
    <time_frame>Within 3 months after corticosteroid taper</time_frame>
    <description>Will be estimated and compared between the two treatment arms using chi-square test.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Endoscopic remission (Mayo Clinic sub-score 0-1) of immune-related diarrhea/colitis</measure>
    <time_frame>At 4 and 8 weeks after initiation of infliximab or vedolizumab treatment</time_frame>
    <description>Will be compared between the two treatment arms.</description>
  </other_outcome>
  <other_outcome>
    <measure>Histological remission (resolution of active inflammation) of immune-related diarrhea/colitis</measure>
    <time_frame>At 8 weeks after initiation of infliximab or vedolizumab treatment</time_frame>
    <description>Will be compared between the two treatment arms.</description>
  </other_outcome>
  <other_outcome>
    <measure>Time duration to achieve clinical remission/response</measure>
    <time_frame>From initiation of infliximab or vedolizumab treatment to clinical remission/response or last follow-up, assessed up to 3 months</time_frame>
    <description>Will be estimated using the method of Kaplan and Meier. Comparisons of the time-to-event endpoint by important subgroups will be made using the log-rank tests.</description>
  </other_outcome>
  <other_outcome>
    <measure>Overall survival</measure>
    <time_frame>From the initiation of infliximab or vedolizumab treatment till death or last follow-up, assessed up to 3 months</time_frame>
    <description>Will be estimated using the method of Kaplan and Meier.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in levels of cytokines in tissue/blood/stool samples</measure>
    <time_frame>Baseline up to 3 months after infliximab or vedolizumab treatment</time_frame>
    <description>Will be compared using 2-sample t-test.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in frequencies of immune cells in tissue/blood/stool samples</measure>
    <time_frame>Baseline up to 3 months after infliximab or vedolizumab treatment</time_frame>
    <description>Will be compared using 2-sample t-test.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Colitis</condition>
  <condition>Lung Non-Small Cell Carcinoma</condition>
  <condition>Malignant Genitourinary System Neoplasm</condition>
  <condition>Malignant Solid Neoplasm</condition>
  <condition>Melanoma</condition>
  <arm_group>
    <arm_group_label>Arm I (infliximab)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receive infliximab IV over 1 hour once at week 0, 2, 6 for a total of 3 doses in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (vedolizumab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive vedolizumab IV over 1 hour at week 0, 2, 6 for a total of 3 doses in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Infliximab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (infliximab)</arm_group_label>
    <other_name>Avakine</other_name>
    <other_name>cA2</other_name>
    <other_name>Remicade</other_name>
    <other_name>Remsima</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Vedolizumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm II (vedolizumab)</arm_group_label>
    <other_name>Entyvio</other_name>
    <other_name>Immunoglobulin G1, anti-(human integrin LPAM-1 (lymphocyte Peyer''s patch adhesion molecule 1)) (human-Mus musculus heavy chain), disulfide with human-Mus musculus kappa-chain, dimer</other_name>
    <other_name>LDP 02</other_name>
    <other_name>LDP-02</other_name>
    <other_name>LDP02</other_name>
    <other_name>MLN0002</other_name>
    <other_name>MLN02</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients who receive any type of immune checkpoint inhibitor (ICI) therapy&#xD;
&#xD;
          -  Patients with peak grade &gt;= 2 immune-related diarrhea and/or colitis (according to the&#xD;
             Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 within 45 days&#xD;
             prior to initiation of study treatment (infliximab/ vedolizumab)&#xD;
&#xD;
          -  Patients with ability to understand and willingness to sign informed consent&#xD;
&#xD;
          -  Patients with genitourinary cancer or melanoma or non-small cell lung cancer&#xD;
&#xD;
          -  No concern for active concomitant GI infection for immune-related diarrhea and/or&#xD;
             colitis work up at the time of protocol therapy initiation as confirmed by stool tests&#xD;
             or as per the treating physician based on clinical presentation&#xD;
&#xD;
          -  Patient who has been cleared for enrollment by Infectious Diseases consultant or&#xD;
             treating physician if positive infection workup or screening tests (e.g. lifelong&#xD;
             positive T-spot due to BCG inoculation, chronic colonization) prior to initiation of&#xD;
             diarrhea/colitis treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients younger than 18 years of age&#xD;
&#xD;
          -  Patients with persistent gastrointestinal infection confirmed with positive testing&#xD;
             despite completing 5 days of antibiotics&#xD;
&#xD;
          -  Patients are on concurrent immunosuppressive therapies other than what will be given&#xD;
             for colitis&#xD;
&#xD;
          -  Patients with preexisting activehistory of inflammatory bowel disease and/or radiation&#xD;
             enterocolitis with active disease status at the time of study treatment initiation&#xD;
&#xD;
          -  Pregnant and breastfeeding women, and&#xD;
&#xD;
          -  Women of child-bearing potential who have positive urine or serum pregnancy test or&#xD;
             refuse to do pregnancy test unless last menstrual cycle was &gt; 1 year prior to consent&#xD;
             and/ or clear documentation states that patient is peri- or post-menopausal or there&#xD;
             was recent supporting objective evidence of 'no pregnancy' status (e.g. blood or&#xD;
             imaging) within 30 days prior to initiation of study treatment&#xD;
&#xD;
          -  Patients who develop concurrent non-GI toxicity at the time of study treatment&#xD;
             initiation&#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>Yinghong Wang</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Yinghong Wang</last_name>
    <phone>713-792-7672</phone>
    <email>ywang59@mdanderson.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yinghong Wang</last_name>
      <phone>713-792-7672</phone>
    </contact>
    <investigator>
      <last_name>Yinghong Wang</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>MD Anderson Cancer Center</description>
  </link>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>May 27, 2020</study_first_submitted>
  <study_first_submitted_qc>May 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 29, 2020</study_first_posted>
  <last_update_submitted>March 31, 2023</last_update_submitted>
  <last_update_submitted_qc>March 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 3, 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>Neoplasms</mesh_term>
    <mesh_term>Melanoma</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
    <mesh_term>Colitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infliximab</mesh_term>
    <mesh_term>Vedolizumab</mesh_term>
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Immunoglobulin G</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/NCT04407247
org study id: 2019-0276
secondary id: NCI-2019-04986
secondary id: 2019-0276
nct id: NCT04407247
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase I/II trial studies the side effects of infliximab and vedolizumab and to see how
      well they work in treating inflammation of the colon (colitis) caused by immune checkpoint
      inhibitor therapy in patients with cancer of the genital and urinary organs (genitourinary)
      or melanoma. Monoclonal antibodies, such as infliximab or vedolizumab, may help to treat
      immunotherapy induced colitis/diarrhea. This study may help to identify the optimal treatment
      strategy for immune checkpoint inhibitor-related colitis in patients with genitourinary
      cancer or melanoma.
PRIMARY OBJECTIVES:

      I. To compare the efficacy of infliximab and vedolizumab for clinical remission/response of
      immune-related diarrhea and/or colitis.

      II. To assess the safety and tolerability of the treatment for immune-mediated diarrhea
      and/or colitis.

      SECONDARY OBJECTIVES:

      I. To assess the efficacy of infliximab and vedolizumab for clinical remission/response of
      IMC at 4 weeks.

      II. To assess the success of corticosteroid tapering. III. To measure the recurrence rate
      after corticosteroid taper.

      EXPLORATORY OBJECTIVES:

      I. To assess the efficacy of infliximab and vedolizumab to achieve endoscopic remission of
      immune-related diarrhea and/or colitis.

      II. To assess the efficacy of infliximab and vedolizumab to achieve histological remission of
      immune-related diarrhea and/or colitis.

      III. To assess the time duration to achieve the clinical remission/response. IV. To assess
      the long term outcome of cancer. V. To assess immunological, molecular and microbiome changes
      in tissue/blood/stool.

      OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM I: Patients receive infliximab intravenously (IV) over 1 hour once at week 0, 2, 6 for a
      total of 3 doses in the absence of disease progression or unacceptable toxicity.

      ARM II: Patients receive vedolizumab IV over 1 hour once at week 0, 2, 6 for a total of 3
      doses in the absence of disease progression or unacceptable toxicity.

      Patients are followed up weekly for 1 month and then at 2 and 3 months after the treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Clinical remission/response rate of immune-mediated colitis (IMC)
time frame: At 2 weeks after initiation of infliximab or vedolizumab with corticosteroid taper
description: The difference of the remission rate between standard of care (infliximab + corticosteroid) and the treatment with vedolizumab + corticosteroid will be calculated along with the 95% confidence interval.
measure: Treatment-related adverse events
time frame: Within 3 months after initiation of infliximab or vedolizumab
description: Will follow standard reporting guidelines for adverse events. Safety data will be summarized by category, severity and frequency.
measure: Clinical remission/response rate of IMC
time frame: At 4 weeks after initiation of infliximab or vedolizumab with corticosteroid taper
description: Will be estimated and compared between the two treatment arms using chi-square test.
measure: Complete weaning of corticosteroid
time frame: Within 4 weeks after infliximab or vedolizumab initiation without rebound of IMC
description: Will be estimated and compared between the two treatment arms using chi-square test.
measure: Recurrent immune-related diarrhea/colitis
time frame: Within 3 months after corticosteroid taper
description: Will be estimated and compared between the two treatment arms using chi-square test.
measure: Endoscopic remission (Mayo Clinic sub-score 0-1) of immune-related diarrhea/colitis
time frame: At 4 and 8 weeks after initiation of infliximab or vedolizumab treatment
description: Will be compared between the two treatment arms.
measure: Histological remission (resolution of active inflammation) of immune-related diarrhea/colitis
time frame: At 8 weeks after initiation of infliximab or vedolizumab treatment
description: Will be compared between the two treatment arms.
measure: Time duration to achieve clinical remission/response
time frame: From initiation of infliximab or vedolizumab treatment to clinical remission/response or last follow-up, assessed up to 3 months
description: Will be estimated using the method of Kaplan and Meier. Comparisons of the time-to-event endpoint by important subgroups will be made using the log-rank tests.
measure: Overall survival
time frame: From the initiation of infliximab or vedolizumab treatment till death or last follow-up, assessed up to 3 months
description: Will be estimated using the method of Kaplan and Meier.
measure: Change in levels of cytokines in tissue/blood/stool samples
time frame: Baseline up to 3 months after infliximab or vedolizumab treatment
description: Will be compared using 2-sample t-test.
measure: Change in frequencies of immune cells in tissue/blood/stool samples
time frame: Baseline up to 3 months after infliximab or vedolizumab treatment
description: Will be compared using 2-sample t-test.
arm group label: Arm I (infliximab)
arm group type: Active Comparator
description: Patients receive infliximab IV over 1 hour once at week 0, 2, 6 for a total of 3 doses in the absence of disease progression or unacceptable toxicity.
arm group label: Arm II (vedolizumab)
arm group type: Experimental
description: Patients receive vedolizumab IV over 1 hour at week 0, 2, 6 for a total of 3 doses in the absence of disease progression or unacceptable toxicity.
intervention type: Biological
intervention name: Infliximab
description: Given IV
arm group label: Arm I (infliximab)
other name: Avakine
other name: cA2
other name: Remicade
other name: Remsima
intervention type: Biological
intervention name: Vedolizumab
description: Given IV
arm group label: Arm II (vedolizumab)
other name: Entyvio
other name: Immunoglobulin G1, anti-(human integrin LPAM-1 (lymphocyte Peyer''s patch adhesion molecule 1)) (human-Mus musculus heavy chain), disulfide with human-Mus musculus kappa-chain, dimer
other name: LDP 02
other name: LDP-02
other name: LDP02
other name: MLN0002
other name: MLN02
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Yinghong Wang
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
last name: Yinghong Wang
phone: 713-792-7672
email: ywang59@mdanderson.org
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
url: http://www.mdanderson.org
description: MD Anderson Cancer Center
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Melanoma
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Colitis
mesh term: Infliximab
mesh term: Vedolizumab
mesh term: Immunoglobulins
mesh term: Immunoglobulin G