Adaptive Radiation Therapy for Cancer

Overseen By Vanderbilt-Ingram Services for Timely Access

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Vanderbilt-Ingram Cancer Center

Disqualifiers: Brain disease, Uncontrolled illness, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new ways to use MRI and PET imaging to enhance radiation therapy for certain cancers. It aims to understand how tumors in head and neck cancer and brain metastases resist treatment, potentially causing cancer recurrence or progression. Participants will undergo imaging with 18F-fluoromisonidazole, a special imaging agent, to identify areas that might not respond well to radiation. Individuals with measurable tumors from head and neck squamous cell carcinoma or brain metastases from other cancers may be suitable for this study. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking advancements in cancer therapy.

Do I need to stop my current medications for this 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 coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that 18F-fluoromisonidazole, the imaging agent used in this trial, has been studied in several projects. These studies suggest it can help monitor low oxygen levels in tumors and changes related to radiation treatment. However, there isn't enough evidence yet to support its regular use for adjusting radiation doses in head and neck cancer.

MRI (Magnetic Resonance Imaging) is generally well-tolerated because it doesn’t use harmful radiation. It is considered safe for ongoing imaging, which is useful for tracking tumor changes over time.

PET (Positron Emission Tomography) is commonly used in cancer care and has proven to be a safe method for guiding radiation treatment. PET scans involve a small amount of radioactive material, but they are widely used because the benefits for diagnosis and treatment planning outweigh the risks.

Overall, these tools are generally safe and have been used in many studies and clinical settings. They are chosen for trials because they provide important information with a low risk of serious side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it leverages cutting-edge imaging techniques to improve cancer treatment precision. Unlike traditional methods that rely heavily on static imaging, this approach uses 18F-fluoromisonidazole with MRI and PET scans to dynamically assess tumor behavior and response. This could lead to more personalized and effective radiation therapy, potentially improving outcomes for patients with locally advanced squamous cell carcinoma of the head and neck, as well as those with brain metastases. By tailoring treatment in real time, this method could overcome limitations of current standards, offering a promising advancement in cancer care.

What evidence suggests that this trial's treatments could be effective for cancer?

In this trial, participants with locally advanced squamous cell carcinoma of the head and neck or brain metastases will undergo magnetic resonance imaging (MRI) scans and positron emission tomography (PET) scans using the imaging agent 18F-fluoromisonidazole. Research has shown that this special type of scan, called an 18F-fluoromisonidazole PET scan, can help predict the effectiveness of radiation therapy for head-and-neck cancer. This scan identifies low-oxygen areas in tumors, which are often difficult to treat with radiation. Studies have found that detecting these low-oxygen areas before treatment can provide insights into the potential success of the therapy. The scan helps doctors identify tumor parts that might resist treatment, allowing for more effective therapy planning. While promising, further research is needed to confirm these benefits in everyday medical care. ^{1 3 6 7 8}

Who Is on the Research Team?

Evan Osmundson, MD

Principal Investigator

Vanderbilt University/Ingram Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with certain head and neck cancers or brain tumors, who can be measured by scans, have a life expectancy over 6 months, and are in good physical condition. They must not be pregnant, agree to use birth control, and able to consent.

Inclusion Criteria

I have a tumor that can be measured with a scan or clinical exam.

Agreement to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and up until the day after 18F-FMISO administration. Informing treating physician immediately if pregnancy is suspected

I am mostly able to care for myself and carry out daily activities.

Exclusion Criteria

My brain tumor is larger than 3.0 cm.

Pregnant patients

You can't have an MRI if you're very scared of small spaces, have metal objects inside you, or weigh more than 350 pounds.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment Assessment

Participants undergo MRI and PET scans to assess tumor hypoxia using 18F-fluoromisonidazole

1-2 weeks

Treatment

Participants receive standard of care stereotactic radiosurgery guided by MRI-based markers of tumor hypoxia

6-8 weeks

Follow-up

Participants are monitored for tumor recurrence, progression, and radiation necrosis post-treatment

3 months

Long-term Follow-up

Participants are evaluated for long-term effects of treatment on tumor hypoxia and radiation necrosis

4 years

What Are the Treatments Tested in This Trial?

Interventions

• 18F-fluoromisonidazole
• Magnetic Resonance Imaging (MRI)
• Positron Emission Tomography (PET)

Trial Overview

The study tests if new MRI methods combined with PET scans using a tracer called 18F-fluoromisonidazole can predict tumor resistance to radiation therapy due to low oxygen levels in the tumor.

How Is the Trial Designed?

Group I: Locally Advanced Squamous Cell Carcinoma of the Head and Neck Experimental Treatment 3 Interventions

Participants will undergo magnetic resonance imaging (MRI) scans and positron emission tomography (PET) scans and administered the imaging agent 18F-fluoromisonidazole.

Group II: Brain metastases Experimental Treatment 3 Interventions

Participants will undergo magnetic resonance imaging (MRI) scans and positron emission tomography (PET) scans and administered the imaging agent 18F-fluoromisonidazole.

Who Is Running the Clinical Trial?

Vanderbilt-Ingram Cancer Center

Lead Sponsor

Trials

221

Recruited

64,400+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

In a study of 19 acute ischemic stroke patients, FMISO PET scans were able to predict early infarct growth with a sensitivity of 100% and a specificity of 82%, indicating its potential as a reliable imaging tool.

The results showed that increased FMISO uptake was significantly associated with infarct growth, as 8 out of 10 patients with high FMISO uptake experienced growth, while none of the 9 patients without uptake showed any growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

(18)F-fluoromisonidazole (FMISO) Positron Emission Tomography (PET) Predicts Early Infarct Growth in Patients with Acute Ischemic Stroke. Lee, GH., Kim, JS., Oh, SJ., et al.[2017]

Adaptive radiotherapy (ART) enhances treatment accuracy by using real-time MRI to monitor changes in tumor and surrounding structures, allowing for personalized adjustments during radiotherapy without additional radiation exposure.

The integration of functional MRI sequences can provide imaging biomarkers that support both geometric and biological adaptations in treatment, potentially improving outcomes across various tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive Radiotherapy Enabled by MRI Guidance. Hunt, A., Hansen, VN., Oelfke, U., et al.[2022]

In a study of 20 head and neck cancer patients, (18)F-fluoromisonidazole ((18)F-FMISO) PET scans showed a strong correlation in intratumor hypoxia distribution in 71% of patients, indicating its potential for identifying hypoxic regions that contribute to radioresistance.

However, when focusing on specific hypoxic zones, only 46% of patients exhibited strong correlation, suggesting variability in (18)F-FMISO uptake and the need for further research to understand these changes before using single-time-point PET scans for hypoxia-targeted radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reproducibility of intratumor distribution of (18)F-fluoromisonidazole in head and neck cancer. Nehmeh, SA., Lee, NY., Schröder, H., et al.[2021]

Magnetic resonance imaging (MRI)-guided adaptive radiotherapy enhances the precision of radiation treatment by providing real-time anatomical and functional imaging during therapy sessions.

This advanced imaging technique could lead to improved treatment outcomes by allowing for adjustments in radiation delivery based on the patient's changing anatomy throughout the course of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance-guided adaptive radiotherapy: a solution to the future. Kupelian, P., Sonke, JJ.[2022]

The study provides an overview of the development of [18F]fluoromisonidazole ([18F]FMISO) as a radiotracer for imaging hypoxic conditions in tumors, highlighting its importance in assessing oxygen demand in cancer cells for better treatment planning.

A new GMP-compliant method for synthesizing [18F]FMISO achieved a radiochemical yield of 49% in just 48 minutes, with over 99% purity, making it a reliable and efficient option for research and preclinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis of [18F]FMISO, a hypoxia-specific imaging probe for PET, an overview from a radiochemist's perspective. Kniess, T., Zessin, J., Mäding, P., et al.[2023]

This study analyzed 171 MRI scans from 8 patients with locally advanced rectal cancer during neoadjuvant radiochemotherapy, finding that MRI can help predict treatment response, specifically identifying volumetric changes that correlate with pathological complete response (pCR).

The research established that T2- and diffusion-weighted imaging (DWI) volumetric measurements at two and four weeks into treatment were significant predictors of pCR, while average tumor ADC values were not effective in distinguishing between treatment responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring MR regression patterns in rectal cancer during neoadjuvant radiochemotherapy with daily T2- and diffusion-weighted MRI. Bostel, T., Dreher, C., Wollschläger, D., et al.[2021]

MRI-guided radiotherapy (MRgRT) offers superior soft tissue imaging compared to CT, allowing for more precise targeting of tumors and better protection of nearby sensitive organs during treatment for head and neck squamous cell carcinoma (HNSCC).

The integration of adaptive workflows in MRgRT enables real-time adjustments to treatment plans based on changes in tumor size and position, which is crucial for optimizing radiation delivery and minimizing damage to surrounding healthy tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Target Definition in MR-Guided Adaptive Radiotherapy for Head and Neck Cancer. Ridder, M., Raaijmakers, CPJ., Pameijer, FA., et al.[2022]

In a study of 22 patients undergoing radiotherapy, tumor hypoxia identified by 18F-misonidazole PET/CT before treatment was significantly correlated with initial tumor response, indicating its potential as a predictive biomarker for clinical outcomes.

Patients with lower levels of hypoxia (measured by SUVmax, T/M ratios, and hypoxic volume) had significantly better overall survival and loco-regional control rates compared to those with higher levels, suggesting that assessing tumor hypoxia can guide treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor Hypoxia Detected by 18F-fluoromisonidazole Positron Emission Tomography (FMISO PET) as a Prognostic Indicator of Radiotherapy (RT). Tachibana, I., Nishimura, Y., Hanaoka, K., et al.[2018]

MRI screening for women at high familial risk of breast cancer is approximately twice as sensitive as X-ray mammography, allowing for earlier detection of smaller, node-negative lesions.

The findings from the UK MARIBS study and other comparative studies have led to updated screening recommendations for high-risk women, emphasizing the importance of MRI in their screening protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breast cancer screening in women at high risk using MRI. Leach, MO.[2009]

In a study of 320 high-risk women who underwent 757 breast MRI procedures from 2007 to 2013, the number of false-positive findings (harms) decreased with each subsequent MRI, indicating improved screening efficiency over time.

Despite the initial higher rate of false positives, breast MRI continued to successfully detect cancer, with a total of 6 malignancies identified from 75 biopsy procedures, demonstrating its ongoing utility as a screening tool for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time-Related Changes in Yield and Harms of Screening Breast Magnetic Resonance Imaging. Pederson, HJ., O'Rourke, C., Lyons, J., et al.[2015]

Breast MRI is the most sensitive method for detecting breast cancer and is primarily used for screening high-risk patients due to its high cost.

Innovations like fast abbreviated MRI and functional techniques such as diffusion-weighted imaging show promise for improving treatment response monitoring and evaluating disease extent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Breast Magnetic Resonance Imaging: Technique, Indications, and Future Applications. Greenwood, HI., Freimanis, RI., Carpentier, BM., et al.[2018]

Combining MRI with annual mammography significantly improves the ability to rule out cancerous lesions in women at very high risk for breast cancer, with a negative likelihood ratio of 0.14 compared to 0.70 for mammography alone.

The study analyzed 11 prospective studies involving various patient populations, indicating that the dual screening method is more effective in detecting potential breast cancer in high-risk women, particularly those with BRCA1 or BRCA2 mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review: using magnetic resonance imaging to screen women at high risk for breast cancer. Warner, E., Messersmith, H., Causer, P., et al.[2022]

The introduction of MRI alongside mammography for breast cancer screening in high-risk women showed a high sensitivity of 93%, leading to the detection of fewer lymph node-positive cancers compared to mammography alone.

While there was no significant difference in 10-year survival rates between the MRI + mammography and mammography-only groups, the MRI-screened group had a significantly higher survival rate (95.3%) compared to those with no intensive screening (73.7%), indicating a potential benefit of MRI in high-risk populations, especially BRCA2 carriers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRI breast screening in high-risk women: cancer detection and survival analysis. Evans, DG., Kesavan, N., Lim, Y., et al.[2022]

Fluorine-18 fluoromisonidazole (FMISO) effectively identifies hypoxic and radioresistant tumors, showing significantly higher uptake in these tumors compared to control tumors, which suggests its potential as a reliable imaging agent in cancer diagnostics.

The study found that FMISO uptake inversely correlates with methionine uptake, indicating that areas of high FMISO uptake correspond to low metabolic activity, while 2-deoxyglucose (2DG) showed a more uniform distribution, suggesting that combining FMISO with other tracers could enhance the prediction of tumor response to radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the distribution of fluorine-18 fluoromisonidazole, deoxyglucose and methionine in tumour tissue. Kubota, K., Tada, M., Yamada, S., et al.[2019]

A new GPU-accelerated Monte Carlo-based dose verification module for the Unity MR-LINAC was developed, demonstrating high accuracy with a relative dose difference of less than 1.6% in phantom tests and 99.36% agreement in clinical cases.

This module allows for fast and reliable independent dose verification in adaptive radiotherapy, significantly improving quality assurance processes in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and clinical application of a GPU-based Monte Carlo dose verification module and software for 1.5 T MR-LINAC. Cheng, B., Xu, Y., Li, S., et al.[2023]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7616449/

Is there a role for [18F]-FMISO PET to guide dose adaptive ...

Combined uptake of [18F]FDG and [18F]FMISO correlates with radiation therapy outcome in head-and-neck cancer patients. Radiother Oncol. 2006;80:151–6. doi ...

2.

link.springer.com

link.springer.com/article/10.1007/s40336-023-00607-y

Is there a role for [18F]-FMISO PET to guide dose adaptive ...

Our results show that currently there is insufficient evidence to propose [ 18 F]FMISO PET for radiotherapy dose adaptation in HNC in a routine clinical ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC1325034/

Kinetic analysis of dynamic 18F-fluoromisonidazole PET ...

Kinetic analysis of dynamic 18F-fluoromisonidazole PET correlates with radiation treatment outcome in head-and-neck cancer - PMC.

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S0167814022001700

A randomized phase II study using dynamic [18F]FMISO ...

Kinetic analysis of dynamic 18F-fluoromisonidazole PET correlates with radiation treatment outcome in head-and-neck cancer. BMC Cancer, 5 (2005), p. 152. View ...

5.

ar.iiarjournals.org

ar.iiarjournals.org/content/38/3/1775

Tumor Hypoxia Detected by 18F-fluoromisonidazole ...

Tumor hypoxia detected by FMISO PET/CT before RT may predict clinical outcome. Hypoxic tumor cells are considered radioresistant and/or chemoresistant.

6.

sciencedirect.com

sciencedirect.com/science/article/pii/S0753332219333815

18 F-FMISO-based micro PET for imaging of tumor hypoxia ...

The present experiments indicate that 18F-HX4 and 18F-FMISO PET/CT could be used as biomarkers for monitoring tumor hypoxia and radiotherapy-associated changes.

7.

thegreenjournal.com

thegreenjournal.com/article/S0167-8140(22)00170-0/fulltext

A randomized phase II study using dynamic [18F]FMISO ...

This study presents results of a randomized phase II trial on hypoxia dose escalation in head and neck cancer (HNC)

8.

cdn.clinicaltrials.gov

cdn.clinicaltrials.gov/large-docs/13/NCT02471313/Prot_SAP_000.pdf

[18F] FMISO Imaging post TACE CC Protocol

Data collection for this study will include imaging data used to identify acute post-embolization tumor hypoxia, as well as conventional post- ...