Clinical trial NCT03838601: Role of Microbiome as a Biomarkers in Locoregionally-Advanced Oropharyngeal Squamous Cell Carcinoma 2
Official title: Role of Microbiome as a Biomarkers in Locoregionally-Advanced Oropharyngeal Squamous Cell Carcinoma 2 (ROMA LA-OPSCC-2)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Head and Neck Squamous Cell Carcinoma
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: NuBiyota
First posted: 2019-02-12
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Toxicity defined by CTCAE v.5.0.
timeFrame: 1 year
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.
timeFrame: 3 months
Secondary outcomes:
measure: Bacterial composition and diversity between baseline, week 4, end of CRT and 2 month follow-up samples
timeFrame: 4 months
measure: Bacterial composition and diversity of oral and stool samples in ROMA 1 (CRT alone) compared to ROMA 2 (CRT plus MET-4).
timeFrame: 4 months
Other outcomes:
measure: Correlation between blood immune profiling and changes in oral/intestinal microbiome in the context of CRT and MET-4 administration.
timeFrame: 1 year
measure: Correlation between oral/intestinal microbiome and radiomics imaging analysis.
timeFrame: 1 year
measure: Stool and serum metabolomic profiles before/after CRT and MET-4.
timeFrame: 1 year
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: Princess Margaret Cancer Centre
name: Anna Spreafico, MD
role: PRINCIPAL_INVESTIGATOR
References: