MRI + Biomarkers for Throat Cancer

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Disqualifiers: Systemic disease, Previous tumor, Pregnancy, others

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

Compensation: Varies

Number of Visits: 4

60 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to explore biomarker development in patients with newly diagnosed Head and neck squamous cell carcinoma (HNSCC) receiving curative therapy.

Do I need to stop my current medications for the trial?

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 for throat cancer?

Research shows that pimonidazole, a component of the treatment, is effective in identifying hypoxic (low oxygen) areas in tumors, which are important for predicting how well a tumor will respond to radiotherapy. This suggests that using pimonidazole in combination with MRI could help in better targeting and treating throat cancer. ^{1 2 3 4 5}

Is the MRI and Pimonidazole treatment safe for humans?

MRI is generally considered safe for humans as it does not use ionizing radiation. Pimonidazole, used to detect low oxygen levels in tumors, has been tested in humans with no serious adverse events reported, and any mild side effects resolved without intervention. ^{2 6 7 8 9}

How does the MRI + Biomarkers treatment for throat cancer differ from other treatments?

This treatment is unique because it uses advanced MRI techniques to provide detailed images and biomarkers (biological indicators) that help understand the tumor's biology and response to treatment, which is not typically available with standard treatments. ^{6 10 11 12 13}

Eligibility Criteria

This trial is for adults over 18 with a confirmed diagnosis of Head and Neck Squamous Cell Carcinoma, who can lie on their back for an hour and are set to receive curative therapy. They must be able to understand the study details and consent, have decent kidney function, and not have had another solid tumor treated in the last five years or any condition that would exclude them from MRI scans.

Inclusion Criteria

You are able to comprehend both verbal and written instructions relating to the study, as well as provide a signed agreement of consent.

I am willing to have more MRI scans.

My kidneys work well enough (creatinine clearance is 30ml/min or more).

Exclusion Criteria

I was treated for a solid tumor within the last 5 years.

As judged by investigator evidence of systemic disease that makes unsuitable for study

Contra-indication for serial MRI scans

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo a baseline fMRI scan and biopsy of the primary tumor

1 week

1 visit (in-person)

Radiotherapy (Cohort A)

Participants receive radiotherapy with biopsies and fMRI scans at week 2 and optionally at week 4

4 weeks

2-3 visits (in-person)

Surgery (Cohort B)

Participants undergo surgery with MRI scan within one week prior and tumor tissue collection

1 week

1 visit (in-person)

Follow-up

Participants are monitored for changes in fMRI and tumor microenvironment biomarkers

4 weeks

Treatment Details

Interventions

• Head and Neck MRI
• Oral Pimonidazole

Trial Overview The HN-BIO study is testing how well functional MRI (fMRI) imaging combined with a drug called Oral Pimonidazole works as biomarkers in patients undergoing treatment for head and neck cancer. The goal is to improve understanding of the tumor environment which could lead to better treatments.

Participant Groups

Group I: Cohort B Experimental Treatment 2 Interventions

Participants who are to receive standard of care curative surgery will have an MRI scan within one week prior to surgery. Tumor tissue from the surgery will also be collected for research. Oral pimonidazole will be taken the night before surgery.

Group II: Cohort A Experimental Treatment 2 Interventions

Participants who are to receive standard of care radiotherapy will have one biopsy and MRI scan before starting radiotherapy and during week two of radiotherapy. Participants will also have an the option to consent to an additional biopsy and MRI scan during week 4 of radiotherapy. Oral pimonidazole will be taken the night before each biopsy.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Findings from Research

In a study involving 20 patients with untreated locally advanced head and neck cancer, 18F-FMISO-PET scans taken at 2 hours post-injection showed a high correlation with those taken at 4 hours, indicating that earlier imaging can provide reliable data.

The results suggest that the total examination time for FMISO-PET can be reduced by omitting the 4-hour scan without losing important quantitative information, which could improve patient comfort and efficiency in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Optimal Post-Injection Timing of Hypoxic Imaging with 18F-Fluoromisonidazole-PET/CT. Kawamura, M., Yoshimura, M., Shimizu, Y., et al.[2022]

The administration of technetium-99m BRU 59-21 in ten head and neck cancer patients was found to be safe, with only mild adverse events reported, indicating its potential for clinical use.

The uptake of this novel hypoxic marker correlated significantly with pimonidazole staining, suggesting that it effectively identifies tumor hypoxia, which is important for understanding tumor behavior and treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study to identify tumour hypoxia in patients with head and neck cancer using technetium-99m BRU 59-21. Hoebers, FJ., Janssen, HL., Olmos, AV., et al.[2016]

In a study of 17 patients with untreated head and neck squamous cell carcinoma (HNSCC), [(18)F]FMISO-PET imaging was used to assess tumor hypoxia, revealing that high uptake of [(18)F]FMISO was associated with significantly lower local control rates and disease-specific survival rates after treatment.

The results suggest that [(18)F]FMISO-PET can be a useful tool for predicting treatment outcomes in HNSCC, indicating that tumors with high hypoxia may respond poorly to radiotherapy or surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-fluoromisonidazole positron emission tomography before treatment is a predictor of radiotherapy outcome and survival prognosis in patients with head and neck squamous cell carcinoma. Kikuchi, M., Yamane, T., Shinohara, S., et al.[2022]

The study found that the average hypoxic fraction (pHF) in FaDu tumours was about 12%, indicating a significant level of hypoxia, which is important because hypoxic cells are more resistant to radiation therapy.

However, the variability in pHF alone could not fully explain the differences in how these tumours responded to radiation, suggesting that other factors, such as clonogen density, need to be considered to better predict treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does heterogeneity of pimonidazole labelling correspond to the heterogeneity of radiation-response of FaDu human squamous cell carcinoma? Yaromina, A., Hölscher, T., Eicheler, W., et al.[2015]

In a study of 28 locoregionally advanced head-and-neck cancer patients treated with platinum-based chemotherapy and intensity-modulated radiotherapy, excellent locoregional control was achieved despite 90% showing detectable hypoxia on pretreatment PET scans.

The presence or absence of hypoxia, as indicated by mid-treatment PET scans, did not correlate with patient outcomes, suggesting that hypoxia may not be a reliable predictor of treatment success in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective trial incorporating pre-/mid-treatment [18F]-misonidazole positron emission tomography for head-and-neck cancer patients undergoing concurrent chemoradiotherapy. Lee, N., Nehmeh, S., Schöder, H., et al.[2022]

The article focuses on MR imaging for head and neck tumors, providing insights into imaging techniques and their relevance in clinical practice.

The authors clarify that the study is not associated with the two National Institutes of Health grants that were mistakenly referenced, ensuring accurate attribution of funding sources.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correction to: Differentiation of Malignant and Benign Head and Neck Tumors with Amide Proton Transfer-Weighted MR Imaging. Yu, L., Li, C., Luo, X., et al.[2020]

Oral administration of pimonidazole HCl is effective for detecting hypoxia in tumors, showing similar binding efficacy to intravenous administration in a study involving 12 dogs with cancer.

Pimonidazole binding was consistently higher than that of the control marker CCI-103F, indicating its potential as a superior hypoxia marker, particularly in regions with higher pH levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of oral and intravenous pimonidazole in canine tumors using intravenous CCI-103F as a control hypoxia marker. Kleiter, MM., Thrall, DE., Malarkey, DE., et al.[2016]

A prospective feasibility study was conducted to evaluate the use of ferumoxytol as a contrast agent for dynamic contrast-enhanced MRI in patients with node-positive head and neck squamous cell carcinomas (HNSCC) or melanoma, involving five enrolled patients.

The study was prematurely terminated due to an FDA black box warning, but it aimed to provide valuable clinical and imaging data for future research in molecular imaging despite the early halt.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Data from a terminated study on iron oxide nanoparticle magnetic resonance imaging for head and neck tumors. Elhalawani, H., Awan, MJ., Ding, Y., et al.[2021]

The newly developed hypoxia tracer [(18)F]FPIMO showed strong hypoxia-driven retention in tumor cells, achieving impressive retention ratios compared to established tracers, indicating its potential for assessing tumor hypoxia.

Despite its promising retention in vitro, [(18)F]FPIMO demonstrated lower absolute tumor signal and contrast in PET imaging compared to the established tracer [(18)F]FAZA, primarily due to rapid metabolism and high accumulation in liver and kidneys.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET imaging of tumor hypoxia using 18F-labeled pimonidazole. Busk, M., Jakobsen, S., Horsman, MR., et al.[2016]

Dynamic magnetic resonance (MR) imaging was performed on 79 head and neck lesions, but it did not improve the sensitivity for detecting malignancy compared to traditional imaging methods.

While dynamic imaging did not effectively differentiate between benign and malignant lesions, it may help in assessing vascularity and recurrence risk, particularly for lesions with specific signal intensity curve patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dynamic MR imaging in the head and neck. Takashima, S., Noguchi, Y., Okumura, T., et al.[2015]

Magnetic resonance imaging (MRI) is highly effective in predicting the resectability of head and neck tumors near the carotid arteries, achieving 100% sensitivity for identifying unresectable cases.

The study, which included 49 patients, found that tumors involving more than 270 degrees of the carotid artery are likely unresectable, while those involving 270 degrees or less can typically be surgically removed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carotid artery invasion by head and neck masses: prediction with MR imaging. Yousem, DM., Hatabu, H., Hurst, RW., et al.[2004]

Dynamic contrast-enhanced MRI successfully distinguished between tumor and nontumor nodes in the cervical lymph nodes of 21 patients with squamous cell carcinoma, highlighting its potential as a diagnostic tool.

The study identified significant differences in contrast enhancement parameters between tumor and nontumor nodes, suggesting that dynamic imaging can effectively aid in the assessment of cervical lymph node involvement in head and neck cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges in dynamic contrast-enhanced MRI imaging of cervical lymph nodes to detect metastatic disease. Noworolski, SM., Fischbein, NJ., Kaplan, MJ., et al.[2019]

Magnetic resonance imaging (MRI) is essential for evaluating head and neck tumors, providing detailed anatomical information crucial for diagnosing and staging both primary tumors and lymph node metastases.

Advanced MRI techniques, including diffusion and perfusion imaging, offer insights into the biological and physiological characteristics of tumors, helping to identify imaging biomarkers that can inform treatment response and disease follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced magnetic resonance imaging techniques for tumors of the head and neck. Santos Armentia, E., Martín Noguerol, T., Suárez Vega, V.[2021]

References

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

Evaluation of Optimal Post-Injection Timing of Hypoxic Imaging with 18F-Fluoromisonidazole-PET/CT. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Phase 1 study to identify tumour hypoxia in patients with head and neck cancer using technetium-99m BRU 59-21. [2016]

3. Japan pubmed.ncbi.nlm.nih.gov

18F-fluoromisonidazole positron emission tomography before treatment is a predictor of radiotherapy outcome and survival prognosis in patients with head and neck squamous cell carcinoma. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

Does heterogeneity of pimonidazole labelling correspond to the heterogeneity of radiation-response of FaDu human squamous cell carcinoma? [2015]

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

Prospective trial incorporating pre-/mid-treatment [18F]-misonidazole positron emission tomography for head-and-neck cancer patients undergoing concurrent chemoradiotherapy. [2022]

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

Correction to: Differentiation of Malignant and Benign Head and Neck Tumors with Amide Proton Transfer-Weighted MR Imaging. [2020]

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

A comparison of oral and intravenous pimonidazole in canine tumors using intravenous CCI-103F as a control hypoxia marker. [2016]

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

Data from a terminated study on iron oxide nanoparticle magnetic resonance imaging for head and neck tumors. [2021]

9. England pubmed.ncbi.nlm.nih.gov

PET imaging of tumor hypoxia using 18F-labeled pimonidazole. [2016]

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

Dynamic MR imaging in the head and neck. [2015]

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

Carotid artery invasion by head and neck masses: prediction with MR imaging. [2004]

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

Challenges in dynamic contrast-enhanced MRI imaging of cervical lymph nodes to detect metastatic disease. [2019]

13. Spain pubmed.ncbi.nlm.nih.gov

Advanced magnetic resonance imaging techniques for tumors of the head and neck. [2021]