<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/NCT03838601</url>
  </required_header>
  <id_info>
    <org_study_id>ROMA LA-OPSCC-002</org_study_id>
    <nct_id>NCT03838601</nct_id>
  </id_info>
  <brief_title>Role of Microbiome as a Biomarkers in Locoregionally-Advanced Oropharyngeal Squamous Cell Carcinoma 2</brief_title>
  <acronym>ROMA LA-OPSCC2</acronym>
  <official_title>Role of Microbiome as a Biomarkers in Locoregionally-Advanced Oropharyngeal Squamous Cell Carcinoma 2 (ROMA LA-OPSCC-2)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Health Network, Toronto</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>NuBiyota</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Health Network, Toronto</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single-centre feasibility study designed to assess the safety, tolerability and&#xD;
      engraftment of MET-4 bacterial strains when given in combination with chemoradiotherapy&#xD;
      (CRT). The study will involve a prospective cohort of 30 patients diagnosed with&#xD;
      Locoregionally-Advanced Oropharyngeal Squamous Cell Carcinoma (LA-OPSCC) to be treated with&#xD;
      CRT as per standard of care at Princess Margaret Cancer Centre. All patients enrolled will&#xD;
      receive MET-4 in addition to standard CRT. MET-4 is administered orally as an initial daily&#xD;
      loading dose over 2 days followed by a daily maintenance dose of MET-4 and will be&#xD;
      administered until week 4 of CRT or unacceptable toxicity whichever occurs earlier and in the&#xD;
      absence of criteria to discontinue MET-4. This protocol does not determine eligibility to&#xD;
      receive treatment with concurrent CRT. It is anticipated that patient accrual will be&#xD;
      completed within 12 months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Past findings suggest oral microbiome might be used to predict recurrence and response to&#xD;
      therapies, as past studies have shown surgery, radiotherapy and chemotherapy alter the&#xD;
      microbiome, which in turn modulates treatment effectiveness/toxicity.&#xD;
&#xD;
      Microbial Ecosystem Therapeutics (MET) is a new treatment approach developed as an&#xD;
      alternative to fecal transplantation. MET consists of a mixture of pure live cultures of&#xD;
      intestinal bacteria isolated from stool of a healthy donor. MET-1 administered by colonoscopy&#xD;
      was successfully used to treat 2 patients with recurrent Clostridium difficile infection&#xD;
      (rCDI). Thus far, MET-2 has been studied in 14 human patients with rCDI. While the&#xD;
      composition of MET-2 and MET-4 treatments are different, MET-4 contains several of the same&#xD;
      bacteria present in MET-2.&#xD;
&#xD;
      ROMA LA-OPSCC-001 is a minimal risk feasibility study to evaluate the oral and intestinal&#xD;
      microbiome using saliva, oropharyngeal swabs over tumor sites, stool and rectal swabs in&#xD;
      patients with locoregionally-advanced oropharyngeal squamous cell carcinoma (LA-OPSCC)&#xD;
      treated with chemoradiotherapy (CRT). This study involved analysis of samples from a&#xD;
      prospective cohort of up to 30 patients diagnosed with LA-OPSCC treated with CRT. The study&#xD;
      did not involve any therapeutic intervention. ROMA LA-OPSCC-001 is closed to accrual. A total&#xD;
      of 181 samples have been collected. There was similarity in profiles between stool and rectal&#xD;
      swab samples, and also between oropharyngeal swabs over the tumor site and saliva, but&#xD;
      distinct by anatomical site, indicating that these sample types are able to resolve&#xD;
      similarities by subject but distinguish anatomical compartments.&#xD;
&#xD;
      This data supports the study feasibility, compliance of sample acquisition and technical&#xD;
      proficiency of characterizing the taxa composition at baseline and after CRT by using 4&#xD;
      methods of sample collection and suggest a potential treatment effect on both oral and&#xD;
      intestinal microbiome.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 2, 2019</start_date>
  <completion_date type="Anticipated">August 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>N/A</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>Toxicity defined by CTCAE v.5.0.</measure>
    <time_frame>1 year</time_frame>
    <description>Safety and toxicity profile of MET-4 when administered concurrent to CRT.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Relative abundance of MET-4 associated bacterial strains in stool samples collected at week 4, end of CRT and 2-month follow-up timepoints.</measure>
    <time_frame>3 months</time_frame>
    <description>Presence of MET-4 associated Operational taxonomic units (OTUs) in stool samples at specified timepoints.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Bacterial composition and diversity between baseline, week 4, end of CRT and 2 month follow-up samples</measure>
    <time_frame>4 months</time_frame>
    <description>DNA extraction from swabs/stool using Zymo Bacterial DNA Mini Prep, then 16S rRNA amplification and high throughput sequencing using Illumina Miseq to create an amplicon library from individual samples, then bioinformatic analysis, then shotgun metagenomics sequencing on an Illumina NextSeq, strain and species-specific qPCR for MET isolates and Nanostring nucleic acid detection using a custom array designed to quantitate MET-4 species will be performed in stool samples collected.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bacterial composition and diversity of oral and stool samples in ROMA 1 (CRT alone) compared to ROMA 2 (CRT plus MET-4).</measure>
    <time_frame>4 months</time_frame>
    <description>DNA extraction from swabs/stool using Zymo Bacterial DNA Mini Prep, then 16S rRNA amplification and high throughput sequencing using Illumina Miseq to create an amplicon library from individual samples, then bioinformatic analysis, then shotgun metagenomics sequencing on an Illumina NextSeq, strain and species-specific qPCR for MET isolates and Nanostring nucleic acid detection using a custom array designed to quantitate MET-4 species will be performed in stool samples collected.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Correlation between blood immune profiling and changes in oral/intestinal microbiome in the context of CRT and MET-4 administration.</measure>
    <time_frame>1 year</time_frame>
    <description>Immune profiling at specified timepoints.</description>
  </other_outcome>
  <other_outcome>
    <measure>Correlation between oral/intestinal microbiome and radiomics imaging analysis.</measure>
    <time_frame>1 year</time_frame>
    <description>Tumor radiomic signatures before and after CRT.</description>
  </other_outcome>
  <other_outcome>
    <measure>Stool and serum metabolomic profiles before/after CRT and MET-4.</measure>
    <time_frame>1 year</time_frame>
    <description>Metabolomics correlates at specified timepoints.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Head and Neck Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>MET-4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects diagnosed with Locoregionally-Advanced Oropharyngeal Squamous Cell Carcinoma (LA-OPSCC) will receive treatment with MET-4 in addition to standard of care CRT. MET-4 is administered orally as an initial daily loading dose over 2 days followed by a daily maintenance dose of MET-4 and will be administered until week 4 of CRT or unacceptable toxicity whichever occurs earlier and in the absence of criteria to discontinue MET-4.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MET-4</intervention_name>
    <description>Microbial Ecosystem Therapeutics (MET) is a new treatment approach developed as an alternative to fecal transplantation. Unlike donor stool used in fecal transplants, which are incompletely characterised complex communities of microbes and associated metabolites and fecal material, MET consists of a defined mixture of pure live cultures of intestinal bacteria isolated from a stool sample of a healthy donor.</description>
    <arm_group_label>MET-4</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed written and voluntary informed consent.&#xD;
&#xD;
          2. Patient must be willing and able to provide:&#xD;
&#xD;
             -Oropharyngeal swab, stool and blood specimen at protocol specified time points.&#xD;
&#xD;
          3. Age &gt; 18 years, male or female.&#xD;
&#xD;
          4. Patient must be diagnosed with histologically confirmed squamous cell carcinoma of the&#xD;
             oropharynx (soft palate, tonsils, base of tongue).&#xD;
&#xD;
          5. Patients must be eligible for curative-intent concurrent treatment with radiotherapy&#xD;
             and chemotherapy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any condition that, in the opinion of the Investigator, would interfere with patient&#xD;
             safety, or evaluation of the collected specimen and interpretation of study result.&#xD;
&#xD;
          2. Subjects unable to swallow orally administered medications or any subjects with&#xD;
             gastrointestinal disorders likely to interfere with absorption (e.g. bowel&#xD;
             obstruction, short gut syndrome, blind loop syndrome, ileostomy etc). Subjects with&#xD;
             colostomies may be enrolled.&#xD;
&#xD;
          3. Pregnant or planning to get pregnant in the next 6 months.&#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>Anna Spreafico, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Princess Margaret Cancer Centre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Princess Margaret Cancer Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>February 5, 2019</study_first_submitted>
  <study_first_submitted_qc>February 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 12, 2019</study_first_posted>
  <last_update_submitted>January 8, 2023</last_update_submitted>
  <last_update_submitted_qc>January 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 10, 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</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03838601
org study id: ROMA LA-OPSCC-002
nct id: NCT03838601
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a single-centre feasibility study designed to assess the safety, tolerability and
      engraftment of MET-4 bacterial strains when given in combination with chemoradiotherapy
      (CRT). The study will involve a prospective cohort of 30 patients diagnosed with
      Locoregionally-Advanced Oropharyngeal Squamous Cell Carcinoma (LA-OPSCC) to be treated with
      CRT as per standard of care at Princess Margaret Cancer Centre. All patients enrolled will
      receive MET-4 in addition to standard CRT. MET-4 is administered orally as an initial daily
      loading dose over 2 days followed by a daily maintenance dose of MET-4 and will be
      administered until week 4 of CRT or unacceptable toxicity whichever occurs earlier and in the
      absence of criteria to discontinue MET-4. This protocol does not determine eligibility to
      receive treatment with concurrent CRT. It is anticipated that patient accrual will be
      completed within 12 months.
Past findings suggest oral microbiome might be used to predict recurrence and response to
      therapies, as past studies have shown surgery, radiotherapy and chemotherapy alter the
      microbiome, which in turn modulates treatment effectiveness/toxicity.

      Microbial Ecosystem Therapeutics (MET) is a new treatment approach developed as an
      alternative to fecal transplantation. MET consists of a mixture of pure live cultures of
      intestinal bacteria isolated from stool of a healthy donor. MET-1 administered by colonoscopy
      was successfully used to treat 2 patients with recurrent Clostridium difficile infection
      (rCDI). Thus far, MET-2 has been studied in 14 human patients with rCDI. While the
      composition of MET-2 and MET-4 treatments are different, MET-4 contains several of the same
      bacteria present in MET-2.

      ROMA LA-OPSCC-001 is a minimal risk feasibility study to evaluate the oral and intestinal
      microbiome using saliva, oropharyngeal swabs over tumor sites, stool and rectal swabs in
      patients with locoregionally-advanced oropharyngeal squamous cell carcinoma (LA-OPSCC)
      treated with chemoradiotherapy (CRT). This study involved analysis of samples from a
      prospective cohort of up to 30 patients diagnosed with LA-OPSCC treated with CRT. The study
      did not involve any therapeutic intervention. ROMA LA-OPSCC-001 is closed to accrual. A total
      of 181 samples have been collected. There was similarity in profiles between stool and rectal
      swab samples, and also between oropharyngeal swabs over the tumor site and saliva, but
      distinct by anatomical site, indicating that these sample types are able to resolve
      similarities by subject but distinguish anatomical compartments.

      This data supports the study feasibility, compliance of sample acquisition and technical
      proficiency of characterizing the taxa composition at baseline and after CRT by using 4
      methods of sample collection and suggest a potential treatment effect on both oral and
      intestinal microbiome.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Toxicity defined by CTCAE v.5.0.
time frame: 1 year
description: Safety and toxicity profile of MET-4 when administered concurrent to CRT.
measure: Relative abundance of MET-4 associated bacterial strains in stool samples collected at week 4, end of CRT and 2-month follow-up timepoints.
time frame: 3 months
description: Presence of MET-4 associated Operational taxonomic units (OTUs) in stool samples at specified timepoints.
measure: Bacterial composition and diversity between baseline, week 4, end of CRT and 2 month follow-up samples
time frame: 4 months
description: DNA extraction from swabs/stool using Zymo Bacterial DNA Mini Prep, then 16S rRNA amplification and high throughput sequencing using Illumina Miseq to create an amplicon library from individual samples, then bioinformatic analysis, then shotgun metagenomics sequencing on an Illumina NextSeq, strain and species-specific qPCR for MET isolates and Nanostring nucleic acid detection using a custom array designed to quantitate MET-4 species will be performed in stool samples collected.
measure: Bacterial composition and diversity of oral and stool samples in ROMA 1 (CRT alone) compared to ROMA 2 (CRT plus MET-4).
time frame: 4 months
description: DNA extraction from swabs/stool using Zymo Bacterial DNA Mini Prep, then 16S rRNA amplification and high throughput sequencing using Illumina Miseq to create an amplicon library from individual samples, then bioinformatic analysis, then shotgun metagenomics sequencing on an Illumina NextSeq, strain and species-specific qPCR for MET isolates and Nanostring nucleic acid detection using a custom array designed to quantitate MET-4 species will be performed in stool samples collected.
measure: Correlation between blood immune profiling and changes in oral/intestinal microbiome in the context of CRT and MET-4 administration.
time frame: 1 year
description: Immune profiling at specified timepoints.
measure: Correlation between oral/intestinal microbiome and radiomics imaging analysis.
time frame: 1 year
description: Tumor radiomic signatures before and after CRT.
measure: Stool and serum metabolomic profiles before/after CRT and MET-4.
time frame: 1 year
description: Metabolomics correlates at specified timepoints.
arm group label: MET-4
arm group type: Experimental
description: Subjects diagnosed with Locoregionally-Advanced Oropharyngeal Squamous Cell Carcinoma (LA-OPSCC) will receive treatment with MET-4 in addition to standard of care CRT. MET-4 is administered orally as an initial daily loading dose over 2 days followed by a daily maintenance dose of MET-4 and will be administered until week 4 of CRT or unacceptable toxicity whichever occurs earlier and in the absence of criteria to discontinue MET-4.
intervention type: Drug
intervention name: MET-4
description: Microbial Ecosystem Therapeutics (MET) is a new treatment approach developed as an alternative to fecal transplantation. Unlike donor stool used in fecal transplants, which are incompletely characterised complex communities of microbes and associated metabolites and fecal material, MET consists of a defined mixture of pure live cultures of intestinal bacteria isolated from a stool sample of a healthy donor.
arm group label: MET-4
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Anna Spreafico, MD
role: Principal Investigator
affiliation: Princess Margaret Cancer Centre
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Squamous Cell Carcinoma of Head and Neck
sharing ipd: No