<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/NCT03819296</url>
  </required_header>
  <id_info>
    <org_study_id>2018-0383</org_study_id>
    <secondary_id>NCI-2018-03437</secondary_id>
    <secondary_id>2018-0383</secondary_id>
    <nct_id>NCT03819296</nct_id>
  </id_info>
  <brief_title>Role of Gut Microbiome and Fecal Transplant on Medication-Induced GI Complications in Patients With Cancer</brief_title>
  <official_title>Role of Microbiome in the Realm of Immune-Checkpoint Inhibitor Induced GI Complications In Cancer Population</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>No</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 trial studies the role of the gut microbiome and effectiveness of a fecal transplant on&#xD;
      medication-induced gastrointestinal (GI) complications in patients with melanoma or&#xD;
      genitourinary cancer. The gut microbiome (the bacteria and microorganisms that live in the&#xD;
      digestive system) may affect whether or not someone develops colitis (inflammation of the&#xD;
      intestines) during cancer treatment with immune-checkpoint inhibitor drugs. Studying samples&#xD;
      of stool, blood, and tissue from patients with melanoma or genitourinary cancer may help&#xD;
      doctors learn more about the effects of treatment on cells, and help doctors understand how&#xD;
      well patients respond to treatment. Treatment with fecal transplantation may help to improve&#xD;
      diarrhea and colitis symptoms.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To compare the difference in stool microbiome pattern between patients who develop&#xD;
      immune-checkpoint inhibitor (ICPI)-related colitis and patients who don't develop&#xD;
      ICPI-related colitis.&#xD;
&#xD;
      II. To compare the difference in stool microbiome pattern in patients who developed&#xD;
      ICPI-related colitis before and after colitis medical treatment.&#xD;
&#xD;
      III. To assess the safety and tolerability and efficacy of fecal microbiota transplantation&#xD;
      (FMT).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To identify and characterize immune profile and genetic factors associated with onset of&#xD;
      ICPI-related colitis in blood and colon tissue.&#xD;
&#xD;
      II. To identify and characterize immune profile and genetic factors in blood and colon tissue&#xD;
      that are associated with quick response of ICPI-related colitis to medical treatment.&#xD;
&#xD;
      III. To characterize the endoscopic and histologic features of ICPI-related colitis before&#xD;
      and after medical treatment.&#xD;
&#xD;
      IV. To document the changes of ICPI-related symptoms and the impact on functioning and&#xD;
      quality of life (QoL) from fecal microbiota transplantation by patient-reported outcomes&#xD;
      (PRO).&#xD;
&#xD;
      V. To assess stool microbiome and cytokine features that are associated with good response to&#xD;
      fecal microbiota transplantation.&#xD;
&#xD;
      VI. To assess the factors in genetic/immune profile obtained from blood and colon tissue that&#xD;
      are associated with good response to fecal microbiota transplantation.&#xD;
&#xD;
      VII. To characterize the endoscopic and histologic features of ICPI-related colitis before&#xD;
      and after fecal microbiota transplantation.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. To identify and characterize immune profile and genetic factors associated with onset of&#xD;
      ICPI-related colitis in inflamed colonic mucosa and its matched normal mucosa.&#xD;
&#xD;
      II. To characterize the immune profile and genetic factors from the colon tissue in these&#xD;
      colitis patients among different histological subtypes.&#xD;
&#xD;
      III. To assess the pattern of stool microbiome that is associated with good tumor response to&#xD;
      ICPI treatment.&#xD;
&#xD;
      IV. To assess the association between stool inflammatory markers (i.e. lactoferrin and&#xD;
      calprotectin) and the severity of endoscopic/histologic inflammation.&#xD;
&#xD;
      V. To assess the sensitivity and specificity of stool inflammatory markers (i.e. lactoferrin&#xD;
      and calprotectin) as an indicators of ICPI-relate colitis response to treatment.&#xD;
&#xD;
      VI. To assess the microbiome pattern that triggers the infections on immunosuppressant&#xD;
      treatment for ICPI colitis.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      PROJECT 1: Patients receive standard of care and undergo collection of stool and blood&#xD;
      samples.&#xD;
&#xD;
      PROJECT 2: Patients receive prednisone, infliximab, or vedolizumab per standard of care and&#xD;
      undergo standard of care endoscopy 2 months after treatment. Patients also undergo collection&#xD;
      of stool, blood, and tissue samples.&#xD;
&#xD;
      PROJECT 3: Patients undergo fecal microbiota transplant (FMT).&#xD;
&#xD;
      After completion of study, patients are followed up periodically.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 21, 2021</start_date>
  <completion_date type="Anticipated">October 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">October 31, 2025</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <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>Difference in stool microbiome pattern</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>The primary endpoint is alpha diversity of bacteria species (measured using inverse Simpson index). It is a measure of diversity which takes into account the number of species present, as well as the relative abundance of each species. As species richness and evenness increase, so diversity increases.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of adverse events (AE) of fecal microbiota transplantation (FMT) (Project 3)</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Adverse events will be recorded by Common Terminology Criteria for Adverse Events version 5 as well as FMT-specific events. All events will be recorded with grade and attribution to FMT. Adverse events that are related to fecal microbiota transplantation will be summarized using frequency and percentage by AE grade, type and attributions.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Immune profile factors associated with onset of ICPI-related colitis in blood and colon tissue</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Immunohistochemistry study for inflammatory markers will be performed on colon biopsies to measure the change in pattern after treatment. Blood and stool samples will be compared before and after immunosuppressive treatment longitudinally and also horizontally between quick response patients and slow/refractory patient.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Genetic factors associated with onset of ICPI-related colitis in blood and colon tissue</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Genomic bacterial DNA will be extracted from fecal samples, with the addition of a bead-beating lysis step. Genomic 16S ribosomal-RNA V4 variable region will be amplified and sequenced on the Illumina MiSeq platform to obtain the microbiome structure and composition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endoscopic and histologic features of ICPI-related colitis before and after medical treatment</measure>
    <time_frame>Baseline up to 1 year</time_frame>
    <description>We will assess the resolution of the following endoscopic presentations of ICPI-related colitis including large, deep ulcerations, erosions, diffuse or patchy erythema, inflammatory exudate, loss of vascular pattern, aphthae, and edema after medical treatment.&#xD;
We will assess the resolution of the following histological features of acute colitis and lymphocytic colitis including neutrophilic infiltration, cryptitis, crypt abscess, eosinophilia, intraepithelial apoptosis, and increased intraepithelial lymphocytic infiltration after medical treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of ICPI-related symptoms</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>We will use MD Anderson Symptom Inventory (MDASI)-Colitis module to capture ICPI-related symptoms, which include 22 physical, psychological, and cognitive symptoms and colitis related symptoms. The ratings are on 0-10 numeric scales, ranging from &quot;not present&quot; to &quot;as bad as you can imagine.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of quality of life (QoL)</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>MD Anderson Symptom Inventory (MDASI)-Colitis module includes 6 symptom interference items which could capture the impact of therapy on patient's physical and affective functioning. The ratings are on 0-10 numeric scales, ranging from &quot;did not interfere &quot; to &quot;interfered completely &quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine features that are associated with good response to FMT</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>We will compare the levels of many cytokines/chemokines by Luminex assays including IL-6, IL-17A, TNF-α, etc. between patients with good response and poor response to FMT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Genetic factors associated with onset of ICPI-related colitis in blood and colon tissue</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Genomic bacterial DNA will be extracted from fecal samples, with the addition of a bead-beating lysis step. Genomic 16S ribosomal-RNA V4 variable region will be amplified and sequenced on the Illumina MiSeq platform to obtain the microbiome structure and composition. We will evaluate these factors between patients with good response and poor response to FMT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of endoscopic and histologic features of ICPI-related colitis before and after fecal microbiota transplantation</measure>
    <time_frame>Baseline up to 1 year</time_frame>
    <description>We will assess the resolution of the following endoscopic presentations of ICPI-related colitis including large, deep ulcerations, erosions, diffuse or patchy erythema, inflammatory exudate, loss of vascular pattern, aphthae, and edema after FMT.&#xD;
We will assess the resolution of the following histological features of acute colitis and lymphocytic colitis including neutrophilic infiltration, cryptitis, crypt abscess, eosinophilia, intraepithelial apoptosis, and increased intraepithelial lymphocytic infiltration after FMT.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">800</enrollment>
  <condition>Clinical Stage 0 Cutaneous Melanoma AJCC v8</condition>
  <condition>Clinical Stage I Cutaneous Melanoma AJCC v8</condition>
  <condition>Clinical Stage IA Cutaneous Melanoma AJCC v8</condition>
  <condition>Clinical Stage IB Cutaneous Melanoma AJCC v8</condition>
  <condition>Clinical Stage II Cutaneous Melanoma AJCC v8</condition>
  <condition>Clinical Stage IIA Cutaneous Melanoma AJCC v8</condition>
  <condition>Clinical Stage IIB Cutaneous Melanoma AJCC v8</condition>
  <condition>Clinical Stage IIC Cutaneous Melanoma AJCC v8</condition>
  <condition>Clinical Stage III Cutaneous Melanoma AJCC v8</condition>
  <condition>Clinical Stage IV Cutaneous Melanoma AJCC v8</condition>
  <condition>Colitis</condition>
  <condition>Lung Non-Small Cell Carcinoma</condition>
  <condition>Malignant Genitourinary System Neoplasm</condition>
  <condition>Malignant Solid Neoplasm</condition>
  <condition>Pathologic Stage 0 Cutaneous Melanoma AJCC v8</condition>
  <condition>Pathologic Stage I Cutaneous Melanoma AJCC v8</condition>
  <condition>Pathologic Stage IA Cutaneous Melanoma AJCC v8</condition>
  <condition>Pathologic Stage IB Cutaneous Melanoma AJCC v8</condition>
  <condition>Pathologic Stage II Cutaneous Melanoma AJCC v8</condition>
  <condition>Pathologic Stage IIA Cutaneous Melanoma AJCC v8</condition>
  <condition>Pathologic Stage IIB Cutaneous Melanoma AJCC v8</condition>
  <condition>Pathologic Stage IIC Cutaneous Melanoma AJCC v8</condition>
  <condition>Pathologic Stage III Cutaneous Melanoma AJCC v8</condition>
  <condition>Pathologic Stage IIIA Cutaneous Melanoma AJCC v8</condition>
  <condition>Pathologic Stage IIIB Cutaneous Melanoma AJCC v8</condition>
  <condition>Pathologic Stage IIIC Cutaneous Melanoma AJCC v8</condition>
  <condition>Pathologic Stage IIID Cutaneous Melanoma AJCC v8</condition>
  <condition>Pathologic Stage IV Cutaneous Melanoma AJCC v8</condition>
  <condition>Stage 0 Lung Cancer AJCC v8</condition>
  <condition>Stage I Lung Cancer AJCC v8</condition>
  <condition>Stage IA1 Lung Cancer AJCC v8</condition>
  <condition>Stage IA2 Lung Cancer AJCC v8</condition>
  <condition>Stage IA3 Lung Cancer AJCC v8</condition>
  <condition>Stage IB Lung Cancer AJCC v8</condition>
  <condition>Stage II Lung Cancer AJCC v8</condition>
  <condition>Stage IIA Lung Cancer AJCC v8</condition>
  <condition>Stage IIB Lung Cancer AJCC v8</condition>
  <condition>Stage III Lung Cancer AJCC v8</condition>
  <condition>Stage IIIA Lung Cancer AJCC v8</condition>
  <condition>Stage IIIB Lung Cancer AJCC v8</condition>
  <condition>Stage IIIC Lung Cancer AJCC v8</condition>
  <condition>Stage IV Lung Cancer AJCC v8</condition>
  <condition>Stage IVA Lung Cancer AJCC v8</condition>
  <condition>Stage IVB Lung Cancer AJCC v8</condition>
  <arm_group>
    <arm_group_label>Supportive Care (standard of care, sample collection, FMT)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PROJECT 1: Patients receive standard of care and undergo collection of stool and blood samples.&#xD;
PROJECT 2: Patients receive prednisone, infliximab, or vedolizumab per standard of care and undergo standard of care endoscopy 2 months after treatment. Patients also undergo collection of stool, blood, and tissue samples.&#xD;
PROJECT 3: Patients undergo FMT.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Best Practice</intervention_name>
    <description>Receive standard of care</description>
    <arm_group_label>Supportive Care (standard of care, sample collection, FMT)</arm_group_label>
    <other_name>standard of care</other_name>
    <other_name>standard therapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Biospecimen Collection</intervention_name>
    <description>Undergo collection of stool, blood, and tissue samples</description>
    <arm_group_label>Supportive Care (standard of care, sample collection, FMT)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Endoscopic Procedure</intervention_name>
    <description>Undergo endoscopy</description>
    <arm_group_label>Supportive Care (standard of care, sample collection, FMT)</arm_group_label>
    <other_name>Endoscopic Examination</other_name>
    <other_name>Endoscopy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Fecal Microbiota Transplantation</intervention_name>
    <description>Undergo FMT</description>
    <arm_group_label>Supportive Care (standard of care, sample collection, FMT)</arm_group_label>
    <other_name>Fecal Material Transplantation</other_name>
    <other_name>Fecal Transplantation</other_name>
    <other_name>FMT</other_name>
    <other_name>Poo Transplant</other_name>
    <other_name>Poop Transplant</other_name>
    <other_name>Stool Transplant</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Infliximab</intervention_name>
    <description>Given intravenously (IV)</description>
    <arm_group_label>Supportive Care (standard of care, sample collection, FMT)</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>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Supportive Care (standard of care, sample collection, FMT)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisone</intervention_name>
    <description>Given orally</description>
    <arm_group_label>Supportive Care (standard of care, sample collection, FMT)</arm_group_label>
    <other_name>.delta.1-Cortisone</other_name>
    <other_name>1, 2-Dehydrocortisone</other_name>
    <other_name>Adasone</other_name>
    <other_name>Cortancyl</other_name>
    <other_name>Dacortin</other_name>
    <other_name>DeCortin</other_name>
    <other_name>Decortisyl</other_name>
    <other_name>Decorton</other_name>
    <other_name>Delta 1-Cortisone</other_name>
    <other_name>Delta-Dome</other_name>
    <other_name>Deltacortene</other_name>
    <other_name>Deltacortisone</other_name>
    <other_name>Deltadehydrocortisone</other_name>
    <other_name>Deltasone</other_name>
    <other_name>Deltison</other_name>
    <other_name>Deltra</other_name>
    <other_name>Econosone</other_name>
    <other_name>Lisacort</other_name>
    <other_name>Meprosona-F</other_name>
    <other_name>Metacortandracin</other_name>
    <other_name>Meticorten</other_name>
    <other_name>Ofisolona</other_name>
    <other_name>Orasone</other_name>
    <other_name>Panafcort</other_name>
    <other_name>Panasol-S</other_name>
    <other_name>Paracort</other_name>
    <other_name>Perrigo Prednisone</other_name>
    <other_name>PRED</other_name>
    <other_name>Predicor</other_name>
    <other_name>Predicorten</other_name>
    <other_name>Prednicen-M</other_name>
    <other_name>Prednicort</other_name>
    <other_name>Prednidib</other_name>
    <other_name>Prednilonga</other_name>
    <other_name>Predniment</other_name>
    <other_name>Prednisone Intensol</other_name>
    <other_name>Prednisonum</other_name>
    <other_name>Prednitone</other_name>
    <other_name>Promifen</other_name>
    <other_name>Rayos</other_name>
    <other_name>Servisone</other_name>
    <other_name>SK-Prednisone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Vedolizumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Supportive Care (standard of care, sample collection, FMT)</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;
          1. Diagnosis of any stage melanoma, Non-Small Cell Lung Cancer or genitourinary (GU)&#xD;
             malignancies (Project 1).&#xD;
&#xD;
          2. Diagnosis of any cancer type (Projects 2 and 3)&#xD;
&#xD;
          3. Treatment with any ICPI agent&#xD;
&#xD;
          4. Ability to understand and willingness to sign an informed consent form and rate&#xD;
             surveys&#xD;
&#xD;
          5. Life expectancy &gt; 4 months (Project 3)&#xD;
&#xD;
          6. ICPI-related diarrhea and/or colitis of any grade with or without concurrent non- GI&#xD;
             toxicity as the toxicity group (project 1)&#xD;
&#xD;
          7. Patients with no organ toxicity as the control group (project 1)&#xD;
&#xD;
          8. ICPI-related colitis and/or diarrhea of grade ≥ 2 as GI toxicity (initial episode or&#xD;
             recurrence) receiving standard treatment of immunosuppressive agents (steroid,&#xD;
             infliximab, vedolizumab, or ustekinumab) any time during the colitis disease course&#xD;
             until sustained resolution of GI toxicity, or one- year time point after enrollment&#xD;
             (Project 2)&#xD;
&#xD;
          9. ICPI-related colitis and/or diarrhea of grade ≥ 2 as GI toxicity without involvement&#xD;
             of non- GI toxicity within 45 days prior to FMT (Project 3)&#xD;
&#xD;
         10. ICPI-related colitis and/or diarrhea of grade ≥ 2 within 45 days prior to FMT with ANY&#xD;
             of the following characteristics (project 3):&#xD;
&#xD;
             (i) refractory to treatment of steroid and two doses of non-steroidal&#xD;
             immunosuppressants e.g. infliximab, vedolizumab or ustekinumab,&#xD;
&#xD;
             (ii) contraindication for immunosuppressive treatment,&#xD;
&#xD;
             (iii) recurrence after successful initial treatment,&#xD;
&#xD;
             (iv) recurrent symptoms once steroid is tapered down/off or diarrhea/colitis symptoms&#xD;
             are steroid dependent, or&#xD;
&#xD;
             (v) patients with a history of refractory ICPI-related colitis and/or diarrhea to&#xD;
             medical treatment, even if they have improved symptoms from supportive care within 45&#xD;
             days prior to FMT&#xD;
&#xD;
         11. No concern for active concomitant GI infection for the ICPI diarrhea/colitis work up&#xD;
             at the time of protocol therapy initiation as confirmed by stool tests or as per the&#xD;
             treating physician based on clinical presentation (project 3)&#xD;
&#xD;
         12. 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 (project 3)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Age younger than 18 years&#xD;
&#xD;
          2. History of inflammatory bowel disease, and/or radiation enteritis or colitis with&#xD;
             active disease status at the time of study treatment initiation&#xD;
&#xD;
          3. Pregnant and breastfeeding women&#xD;
&#xD;
          4. 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 date of study treatment&#xD;
&#xD;
          5. Patients who develop concurrent non- GI toxicity at the time of FMT treatment (project&#xD;
             3)&#xD;
&#xD;
          6. Patients with active bacterial or fungal infection (Project 3)&#xD;
&#xD;
          7. Donors at risk for monkeypox infection and/ or exposure as determined by a&#xD;
             questionnaire (Project 3)&#xD;
&#xD;
        Withdrawal Criteria&#xD;
&#xD;
          1. Patients may withdraw from the trial at any time&#xD;
&#xD;
          2. Patients who develop GI perforation or toxic colitis that require surgery from ICPI&#xD;
             colitis&#xD;
&#xD;
          3. In project 3, if the first 30% of cases fail the fecal transplant treatment, then&#xD;
             project 3 will be terminated&#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>Krishna Rajalu, MD</last_name>
    <phone>713-563-6086</phone>
    <email>kvaratharajalu@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>713-563-4382</phone>
      <email>ywang59@mdanderson.org</email>
    </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>June 2023</verification_date>
  <study_first_submitted>January 25, 2019</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>June 29, 2023</last_update_submitted>
  <last_update_submitted_qc>June 29, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 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>Lung Neoplasms</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Melanoma</mesh_term>
    <mesh_term>Skin Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisone</mesh_term>
    <mesh_term>Infliximab</mesh_term>
    <mesh_term>Cortisone</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/NCT03819296
org study id: 2018-0383
secondary id: NCI-2018-03437
secondary id: 2018-0383
nct id: NCT03819296
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This trial studies the role of the gut microbiome and effectiveness of a fecal transplant on
      medication-induced gastrointestinal (GI) complications in patients with melanoma or
      genitourinary cancer. The gut microbiome (the bacteria and microorganisms that live in the
      digestive system) may affect whether or not someone develops colitis (inflammation of the
      intestines) during cancer treatment with immune-checkpoint inhibitor drugs. Studying samples
      of stool, blood, and tissue from patients with melanoma or genitourinary cancer may help
      doctors learn more about the effects of treatment on cells, and help doctors understand how
      well patients respond to treatment. Treatment with fecal transplantation may help to improve
      diarrhea and colitis symptoms.
PRIMARY OBJECTIVES:

      I. To compare the difference in stool microbiome pattern between patients who develop
      immune-checkpoint inhibitor (ICPI)-related colitis and patients who don't develop
      ICPI-related colitis.

      II. To compare the difference in stool microbiome pattern in patients who developed
      ICPI-related colitis before and after colitis medical treatment.

      III. To assess the safety and tolerability and efficacy of fecal microbiota transplantation
      (FMT).

      SECONDARY OBJECTIVES:

      I. To identify and characterize immune profile and genetic factors associated with onset of
      ICPI-related colitis in blood and colon tissue.

      II. To identify and characterize immune profile and genetic factors in blood and colon tissue
      that are associated with quick response of ICPI-related colitis to medical treatment.

      III. To characterize the endoscopic and histologic features of ICPI-related colitis before
      and after medical treatment.

      IV. To document the changes of ICPI-related symptoms and the impact on functioning and
      quality of life (QoL) from fecal microbiota transplantation by patient-reported outcomes
      (PRO).

      V. To assess stool microbiome and cytokine features that are associated with good response to
      fecal microbiota transplantation.

      VI. To assess the factors in genetic/immune profile obtained from blood and colon tissue that
      are associated with good response to fecal microbiota transplantation.

      VII. To characterize the endoscopic and histologic features of ICPI-related colitis before
      and after fecal microbiota transplantation.

      EXPLORATORY OBJECTIVES:

      I. To identify and characterize immune profile and genetic factors associated with onset of
      ICPI-related colitis in inflamed colonic mucosa and its matched normal mucosa.

      II. To characterize the immune profile and genetic factors from the colon tissue in these
      colitis patients among different histological subtypes.

      III. To assess the pattern of stool microbiome that is associated with good tumor response to
      ICPI treatment.

      IV. To assess the association between stool inflammatory markers (i.e. lactoferrin and
      calprotectin) and the severity of endoscopic/histologic inflammation.

      V. To assess the sensitivity and specificity of stool inflammatory markers (i.e. lactoferrin
      and calprotectin) as an indicators of ICPI-relate colitis response to treatment.

      VI. To assess the microbiome pattern that triggers the infections on immunosuppressant
      treatment for ICPI colitis.

      OUTLINE:

      PROJECT 1: Patients receive standard of care and undergo collection of stool and blood
      samples.

      PROJECT 2: Patients receive prednisone, infliximab, or vedolizumab per standard of care and
      undergo standard of care endoscopy 2 months after treatment. Patients also undergo collection
      of stool, blood, and tissue samples.

      PROJECT 3: Patients undergo fecal microbiota transplant (FMT).

      After completion of study, patients are followed up periodically.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Difference in stool microbiome pattern
time frame: Up to 1 year
description: The primary endpoint is alpha diversity of bacteria species (measured using inverse Simpson index). It is a measure of diversity which takes into account the number of species present, as well as the relative abundance of each species. As species richness and evenness increase, so diversity increases.
measure: Incidence of adverse events (AE) of fecal microbiota transplantation (FMT) (Project 3)
time frame: Up to 1 year
description: Adverse events will be recorded by Common Terminology Criteria for Adverse Events version 5 as well as FMT-specific events. All events will be recorded with grade and attribution to FMT. Adverse events that are related to fecal microbiota transplantation will be summarized using frequency and percentage by AE grade, type and attributions.
measure: Immune profile factors associated with onset of ICPI-related colitis in blood and colon tissue
time frame: Up to 1 year
description: Immunohistochemistry study for inflammatory markers will be performed on colon biopsies to measure the change in pattern after treatment. Blood and stool samples will be compared before and after immunosuppressive treatment longitudinally and also horizontally between quick response patients and slow/refractory patient.
measure: Genetic factors associated with onset of ICPI-related colitis in blood and colon tissue
time frame: Up to 1 year
description: Genomic bacterial DNA will be extracted from fecal samples, with the addition of a bead-beating lysis step. Genomic 16S ribosomal-RNA V4 variable region will be amplified and sequenced on the Illumina MiSeq platform to obtain the microbiome structure and composition.
measure: Endoscopic and histologic features of ICPI-related colitis before and after medical treatment
time frame: Baseline up to 1 year
description: We will assess the resolution of the following endoscopic presentations of ICPI-related colitis including large, deep ulcerations, erosions, diffuse or patchy erythema, inflammatory exudate, loss of vascular pattern, aphthae, and edema after medical treatment.
We will assess the resolution of the following histological features of acute colitis and lymphocytic colitis including neutrophilic infiltration, cryptitis, crypt abscess, eosinophilia, intraepithelial apoptosis, and increased intraepithelial lymphocytic infiltration after medical treatment.
measure: Changes of ICPI-related symptoms
time frame: Up to 1 year
description: We will use MD Anderson Symptom Inventory (MDASI)-Colitis module to capture ICPI-related symptoms, which include 22 physical, psychological, and cognitive symptoms and colitis related symptoms. The ratings are on 0-10 numeric scales, ranging from "not present" to "as bad as you can imagine.
measure: Changes of quality of life (QoL)
time frame: Up to 1 year
description: MD Anderson Symptom Inventory (MDASI)-Colitis module includes 6 symptom interference items which could capture the impact of therapy on patient's physical and affective functioning. The ratings are on 0-10 numeric scales, ranging from "did not interfere " to "interfered completely ".
measure: Cytokine features that are associated with good response to FMT
time frame: Up to 1 year
description: We will compare the levels of many cytokines/chemokines by Luminex assays including IL-6, IL-17A, TNF-α, etc. between patients with good response and poor response to FMT.
measure: Genetic factors associated with onset of ICPI-related colitis in blood and colon tissue
time frame: Up to 1 year
description: Genomic bacterial DNA will be extracted from fecal samples, with the addition of a bead-beating lysis step. Genomic 16S ribosomal-RNA V4 variable region will be amplified and sequenced on the Illumina MiSeq platform to obtain the microbiome structure and composition. We will evaluate these factors between patients with good response and poor response to FMT.
measure: Changes of endoscopic and histologic features of ICPI-related colitis before and after fecal microbiota transplantation
time frame: Baseline up to 1 year
description: We will assess the resolution of the following endoscopic presentations of ICPI-related colitis including large, deep ulcerations, erosions, diffuse or patchy erythema, inflammatory exudate, loss of vascular pattern, aphthae, and edema after FMT.
We will assess the resolution of the following histological features of acute colitis and lymphocytic colitis including neutrophilic infiltration, cryptitis, crypt abscess, eosinophilia, intraepithelial apoptosis, and increased intraepithelial lymphocytic infiltration after FMT.
arm group label: Supportive Care (standard of care, sample collection, FMT)
arm group type: Experimental
description: PROJECT 1: Patients receive standard of care and undergo collection of stool and blood samples.
PROJECT 2: Patients receive prednisone, infliximab, or vedolizumab per standard of care and undergo standard of care endoscopy 2 months after treatment. Patients also undergo collection of stool, blood, and tissue samples.
PROJECT 3: Patients undergo FMT.
intervention type: Other
intervention name: Best Practice
description: Receive standard of care
arm group label: Supportive Care (standard of care, sample collection, FMT)
other name: standard of care
other name: standard therapy
intervention type: Other
intervention name: Biospecimen Collection
description: Undergo collection of stool, blood, and tissue samples
arm group label: Supportive Care (standard of care, sample collection, FMT)
intervention type: Procedure
intervention name: Endoscopic Procedure
description: Undergo endoscopy
arm group label: Supportive Care (standard of care, sample collection, FMT)
other name: Endoscopic Examination
other name: Endoscopy
intervention type: Procedure
intervention name: Fecal Microbiota Transplantation
description: Undergo FMT
arm group label: Supportive Care (standard of care, sample collection, FMT)
other name: Fecal Material Transplantation
other name: Fecal Transplantation
other name: FMT
other name: Poo Transplant
other name: Poop Transplant
other name: Stool Transplant
intervention type: Biological
intervention name: Infliximab
description: Given intravenously (IV)
arm group label: Supportive Care (standard of care, sample collection, FMT)
other name: Avakine
other name: cA2
other name: Remicade
other name: Remsima
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Ancillary studies
arm group label: Supportive Care (standard of care, sample collection, FMT)
intervention type: Drug
intervention name: Prednisone
description: Given orally
arm group label: Supportive Care (standard of care, sample collection, FMT)
other name: .delta.1-Cortisone
other name: 1, 2-Dehydrocortisone
other name: Adasone
other name: Cortancyl
other name: Dacortin
other name: DeCortin
other name: Decortisyl
other name: Decorton
other name: Delta 1-Cortisone
other name: Delta-Dome
other name: Deltacortene
other name: Deltacortisone
other name: Deltadehydrocortisone
other name: Deltasone
other name: Deltison
other name: Deltra
other name: Econosone
other name: Lisacort
other name: Meprosona-F
other name: Metacortandracin
other name: Meticorten
other name: Ofisolona
other name: Orasone
other name: Panafcort
other name: Panasol-S
other name: Paracort
other name: Perrigo Prednisone
other name: PRED
other name: Predicor
other name: Predicorten
other name: Prednicen-M
other name: Prednicort
other name: Prednidib
other name: Prednilonga
other name: Predniment
other name: Prednisone Intensol
other name: Prednisonum
other name: Prednitone
other name: Promifen
other name: Rayos
other name: Servisone
other name: SK-Prednisone
intervention type: Biological
intervention name: Vedolizumab
description: Given IV
arm group label: Supportive Care (standard of care, sample collection, FMT)
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: Krishna Rajalu, MD
phone: 713-563-6086
email: kvaratharajalu@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: Lung Neoplasms
mesh term: Neoplasms
mesh term: Melanoma
mesh term: Skin Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Prednisone
mesh term: Infliximab
mesh term: Cortisone
mesh term: Vedolizumab
mesh term: Immunoglobulins
mesh term: Immunoglobulin G