MET-4 with Chemoradiotherapy for Throat Cancer

(ROMA LA-OPSCC2 Trial)

Overseen By Anna Spreafico, MD PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Disqualifiers: Pregnancy, Swallowing disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called MET-4, administered alongside standard chemoradiotherapy (CRT) for throat cancer, specifically Locoregionally-Advanced Oropharyngeal Squamous Cell Carcinoma (LA-OPSCC). The main goal is to assess the safety and efficacy of MET-4 in combination with CRT. Participants suitable for this trial have been diagnosed with this specific throat cancer and are eligible for CRT with a curative intent. As an unphased trial, it offers patients the chance to contribute to groundbreaking research that could lead to new treatment options.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What prior data suggests that MET-4 is safe for use with chemoradiotherapy?

Research is investigating the safety of MET-4 when combined with chemoradiotherapy (CRT) for throat cancer. Although specific information about MET-4's safety in humans is not yet available, the study focuses on safety and closely monitors any side effects.

CRT can cause serious side effects. One study found that 71% of patients experienced severe side effects from CRT. Researchers are testing MET-4 to determine if it can be safely used with CRT. As this study is in an early phase, MET-4 is relatively new in this context. While there is hope for its safety, some unknowns remain. Always consult your doctor to determine if this trial is suitable for you. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard of care for Locoregionally-Advanced Oropharyngeal Squamous Cell Carcinoma, which typically involves chemoradiotherapy (CRT), MET-4 offers something new by being an oral treatment. Researchers are excited because MET-4 is designed to be taken alongside CRT, potentially enhancing the treatment's effectiveness against throat cancer. This combination could mean better outcomes with a novel approach, as MET-4 is administered as an initial loading dose followed by a maintenance dose, which is a different delivery method compared to traditional treatments. This could lead to reduced toxicity and improved patient experience during treatment.

What evidence suggests that MET-4 might be an effective treatment for throat cancer?

Research has shown that adding MET-4 to the usual treatment for throat cancer, which includes chemotherapy and radiation, might improve outcomes. This trial will evaluate MET-4, a probiotic treatment, in combination with standard chemoradiotherapy for subjects diagnosed with Locoregionally-Advanced Oropharyngeal Squamous Cell Carcinoma (LA-OPSCC). Studies on advanced throat cancer have reported encouraging survival rates, with 86% of patients living for at least five years. MET-4 could enhance the body's response to these treatments by supporting gut health, which is linked to overall immune health. Although MET-4 remains under investigation, early findings suggest it might reduce the risk of cancer recurrence and improve survival when used with standard treatment. ^{5 6 7 8 9}

Who Is on the Research Team?

Anna Spreafico, MD PhD

Principal Investigator

Princess Margaret Cancer Centre

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a specific throat cancer (Locoregionally-Advanced Oropharyngeal Squamous Cell Carcinoma) who can undergo standard chemoradiotherapy. Participants must be able to provide various biological samples and have no conditions affecting study safety or results interpretation, such as gastrointestinal disorders that impact medication absorption.

Inclusion Criteria

I am willing to provide mouth swab, stool, and blood samples when needed.

I am older than 18 years.

Signed written and voluntary informed consent.

Exclusion Criteria

I cannot take pills by mouth or have a gut condition affecting drug absorption, but I can join if I have a colostomy.

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.

Pregnant or planning to get pregnant in the next 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MET-4 in addition to standard chemoradiotherapy (CRT). MET-4 is administered orally as an initial daily loading dose over 2 days followed by a daily maintenance dose until week 4 of CRT or unacceptable toxicity.

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including microbiome and metabolomic profiling.

2 months

Long-term follow-up

Continued monitoring of microbiome and immune profiling, with sample collection and analysis at specified timepoints.

1 year

What Are the Treatments Tested in This Trial?

Interventions

• MET-4

Trial Overview The trial tests the safety and effects of MET-4 bacteria strains alongside usual chemoradiotherapy in treating throat cancer. All patients will receive MET-4 orally, starting with a loading dose followed by maintenance until week 4 of treatment or until side effects become too severe.

How Is the Trial Designed?

Group I: MET-4 Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

NuBiyota

Collaborator

Trials

9

Recruited

240+

Published Research Related to This Trial

Preoperative simultaneous radiation therapy combined with Cisplatin (CTRT) significantly improved treatment outcomes in patients with Stage III/IV head and neck squamous cell carcinoma, showing a 68% complete clinical response compared to 36% in the control group.

CTRT also resulted in lower toxicity rates (45% vs 76% in the control group) and reduced recurrence (33% vs 66%), suggesting it may be a more effective and safer treatment option for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative simultaneous fractionated cisplatin and radiation therapy in the treatment of advanced operable stage III and IV squamous cell carcinoma of the head and neck. Davis, MA., Tyrrell, J., Slotman, GJ., et al.[2019]

Combination therapies for head and neck cancer, including agents like cisplatin and 5-fluorouracil, have shown improved response rates but no significant survival advantage over monotherapy.

Docetaxel has demonstrated promising response rates of 23-42% as a monotherapy and up to 100% when combined with cisplatin and 5-FU, leading to a phase III trial to evaluate its effectiveness in standard neoadjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The chemotherapy of head and neck cancer. de Mulder, PH.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4734935/

Advanced oropharyngeal squamous cell carcinoma Excellent patient outcomes were reported, including a five year overall survival of 86%. Similarly, locoregional recurrences were quite low, with a 90% ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4424158/

Long-term Outcomes after Surgical or Nonsurgical Initial ... We found that the potential for long-term (>10-year) survival among patients with T4 larynx cancer is significant, and that the choice of treatment is ...

3. jamanetwork.com jamanetwork.com/journals/OTOL/articlepdf/2275418/ooi150028.pdf

Treatment Outcomes for T4 Oropharyngeal Squamous Cell ... age (mean 59.8 vs 55.4 years [P = .005]), sex (male, 95% vs 84% [P = .04]), body mass index. (<18.5 [calculated as weight in kilograms ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2780537

Association of Advanced-Stage Oropharyngeal Squamous ... This comparative effectiveness research investigates survival outcomes for chemoradiotherapy vs surgical treatment among patients with ...

5. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.33491

Outcomes of patients with oropharyngeal squamous cell ... The 3-year OS rate was significantly lower in patients receiving IC (75.7%) versus CRT alone (92.9%). In a multicovariate analysis, receipt of ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK563268/

Oropharyngeal Squamous Cell Carcinoma - StatPearls - NCBI Oropharyngeal squamous cell carcinoma, commonly known as throat cancer or tonsil cancer, is a type of head and neck cancer that refers to the cancer of the ...

7. cancer.gov cancer.gov/types/head-and-neck/hp/adult/oropharyngeal-treatment-pdq

Oropharyngeal Cancer Treatment (PDQ®) - NCI Oropharyngeal cancer treatment options may include radiation therapy, surgery, chemoradiation, chemotherapy alone, and immunotherapy.

8. hopkinsmedicine.org hopkinsmedicine.org/health/conditions-and-diseases/oropharyngeal-cancer

Oropharyngeal Cancer There are many types of cancer of the oropharynx. The vast majority are squamous cell carcinomas, which can be divided into two types based on human ...

9. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.3322%2Fcaac.21293

Oral cavity and oropharyngeal squamous cell carcinoma— ... This update presents the latest evidence regarding OC-SCC and OP-SCC. In particular, the authors compare and contrast tumors at these two sites.