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

30 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment MET-4 for throat cancer?

Research suggests that the MET receptor, which MET-4 targets, plays a role in the progression of head and neck cancers, and targeting it could potentially improve treatment outcomes. However, clinical trials specifically evaluating MET-4's effectiveness in throat cancer are still needed to confirm its benefits. ^{1 2 3 4 5}

Is MET-4 with Chemoradiotherapy generally safe for humans?

Research on MET inhibitors, which are related to MET-4, shows they can affect cancer cell growth and movement, but their safety in humans, especially in combination with other treatments, needs more study. Some studies suggest that targeting MET might help with treatment resistance, but the safety profile in clinical settings is not fully established. ^{1 6 7 8 9}

How does the MET-4 treatment differ from other throat cancer treatments?

The MET-4 treatment is unique because it targets the MET receptor, which is involved in cancer cell growth and resistance to traditional therapies like chemotherapy and radiation. By inhibiting MET, this treatment may improve the effectiveness of existing therapies and help overcome treatment resistance in throat cancer. ^{1 7 8 9 10}

What is the purpose of this trial?

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.

Research Team

Anna Spreafico, MD PhD

Principal Investigator

Princess Margaret Cancer Centre

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Biological, diagnostic and therapeutic relevance of the MET receptor signaling in head and neck cancer. [2014]

2. England pubmed.ncbi.nlm.nih.gov

The chemotherapy of head and neck cancer. [2019]

3. United States 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. [2019]

4. Germany pubmed.ncbi.nlm.nih.gov

Organ-preservation (chemo)radiotherapy for T4 laryngeal and hypopharyngeal cancer: is the effort worth? [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Hepatocyte Growth Factor Receptor overexpression predicts reduced survival but its targeting is not effective in unselected HNSCC patients. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Patient-oriented toxicity endpoints after head and neck reirradiation with intensity modulated radiation therapy. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

The MET receptor tyrosine kinase is a potential novel therapeutic target for head and neck squamous cell carcinoma. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Prevalence and clinical impact of Met Y1253D-activating point mutation in radiotherapy-treated squamous cell cancer of the oropharynx. [2009]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Tyrosine Kinase c-MET as Therapeutic Target for Radiosensitization of Head and Neck Squamous Cell Carcinomas. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

c-Met expression is a marker of poor prognosis in patients with locally advanced head and neck squamous cell carcinoma treated with chemoradiation. [2021]