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Role of Microbiome as a Biomarkers in Locoregionally-Advanced Oropharyngeal Squamous Cell Carcinoma 2 (ROMA LA-OPSCC2)

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ClinicalTrials.gov Identifier: NCT03838601
Recruitment Status : Recruiting
First Posted : February 12, 2019
Last Update Posted : September 25, 2019
Sponsor:
Collaborator:
NuBiyota
Information provided by (Responsible Party):
University Health Network, Toronto

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Head and Neck Squamous Cell Carcinoma Drug: MET-4 Not Applicable

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Role of Microbiome as a Biomarkers in Locoregionally-Advanced Oropharyngeal Squamous Cell Carcinoma 2 (ROMA LA-OPSCC-2)
Actual Study Start Date : July 2, 2019
Estimated Primary Completion Date : November 2, 2020
Estimated Study Completion Date : November 2, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: MET-4
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.
Drug: MET-4
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.




Primary Outcome Measures :
  1. Toxicity defined by CTCAE v.5.0. [ Time Frame: 1 year ]
    Safety and toxicity profile of MET-4 when administered concurrent to CRT.

  2. 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 ]
    Presence of MET-4 associated Operational taxonomic units (OTUs) in stool samples at specified timepoints.


Secondary Outcome Measures :
  1. Bacterial composition and diversity between baseline, week 4, end of CRT and 2 month follow-up samples [ Time Frame: 4 months ]
    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.

  2. 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 ]
    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.


Other Outcome Measures:
  1. Correlation between blood immune profiling and changes in oral/intestinal microbiome in the context of CRT and MET-4 administration. [ Time Frame: 1 year ]
    Immune profiling at specified timepoints.

  2. Correlation between oral/intestinal microbiome and radiomics imaging analysis. [ Time Frame: 1 year ]
    Tumor radiomic signatures before and after CRT.

  3. Stool and serum metabolomic profiles before/after CRT and MET-4. [ Time Frame: 1 year ]
    Metabolomics correlates at specified timepoints.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed written and voluntary informed consent.
  2. Patient must be willing and able to provide:

    -Oropharyngeal swab, stool and blood specimen at protocol specified time points.

  3. Age > 18 years, male or female.
  4. Patient must be diagnosed with histologically confirmed squamous cell carcinoma of the oropharynx (soft palate, tonsils, base of tongue).
  5. Patients must be eligible for curative-intent concurrent treatment with radiotherapy and chemotherapy.

Exclusion Criteria:

  1. Any condition that, in the opinion of the Investigator, would interfere with patient safety, or evaluation of the collected specimen and interpretation of study result.
  2. Subjects unable to swallow orally administered medications or any subjects with gastrointestinal disorders likely to interfere with absorption (e.g. bowel obstruction, short gut syndrome, blind loop syndrome, ileostomy etc). Subjects with colostomies may be enrolled.
  3. Pregnant or planning to get pregnant in the next 6 months.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03838601


Contacts
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Contact: Anna Spreafico, MD 416-946-4501 ext 3308 tip@uhn.ca
Contact: Aileen Trang 416-946-4501 ext 7754 aileen.trang@uhn.ca

Locations
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Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Anna Spreafico, MD    416-946-4501 ext 3308    tip@uhn.ca   
Contact: Aileen Trang    416-946-4501 ext 7754    aileen.trang@uhn.ca   
Sponsors and Collaborators
University Health Network, Toronto
NuBiyota
Investigators
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Principal Investigator: Anna Spreafico, MD Princess Margaret Cancer Centre

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Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT03838601    
Other Study ID Numbers: ROMA LA-OPSCC-002
First Posted: February 12, 2019    Key Record Dates
Last Update Posted: September 25, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site