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)

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.

Trial Description

Primary Outcome:

• Toxicity defined by CTCAE v.5.0.
• Relative abundance of MET-4 associated bacterial strains in stool samples collected at week 4, end of CRT and 2-month follow-up timepoints.

Secondary Outcome:

• Bacterial composition and diversity between baseline, week 4, end of CRT and 2 month follow-up samples
• Bacterial composition and diversity of oral and stool samples in ROMA 1 (CRT alone) compared to ROMA 2 (CRT plus MET-4).

Past findings suggest oral microbiome might be used to predict recurrence and response to therapies, as past studies have shown surgery, radiation therapy 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 tumour 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 tumour 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.

View this trial on ClinicalTrials.gov