Advanced PET/MRI Imaging for Breast Cancer

Overseen By Sebastian Eady

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: University of Alabama at Birmingham

Disqualifiers: Pregnancy, Metal implants, others

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

Compensation: Varies

Number of Visits: 10

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new imaging drug, [18F]FMISO, can help doctors assess how well trastuzumab (Herceptin) works alongside chemotherapy in individuals with advanced HER2 positive breast cancer. This study focuses solely on imaging and will not alter any current treatment plans, but it aims to enhance future understanding of breast cancer treatment. Ideal candidates for this trial are those diagnosed with locally advanced HER2 positive breast cancer who have not yet started treatment. Participants will undergo several PET/MRI scans to track changes over time. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Since this study is for imaging purposes only and not a treatment study, it is likely that you can continue your current medications, but you should confirm with the study team.

What prior data suggests that this imaging method is safe for breast cancer patients?

Research has shown that [18F]FMISO, a substance used in PET scans (a type of imaging), is likely safe for humans. Previous studies have used it in medical settings without major safety concerns, indicating that it hasn't caused significant problems or side effects in patients during imaging.

This study does not focus on treatment. Instead, it uses [18F]FMISO to gain insights into how breast cancer treatments like Herceptin work. So far, [18F]FMISO has been generally well-tolerated in imaging, with patients reporting few issues in similar studies. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it uses advanced [18F]FMISO PET/MRI imaging to enhance the understanding of how HER2+ breast cancer responds to treatments like Herceptin. Unlike standard imaging techniques, which often provide limited insight into tumor oxygenation levels, [18F]FMISO PET/MRI can offer more detailed information about tumor hypoxia, a condition where tumor regions are deprived of oxygen and can be more resistant to therapy. By capturing these details before and during treatment, researchers hope to tailor therapies more effectively, potentially improving outcomes for patients with locally advanced HER2+ breast cancer.

What evidence suggests that this imaging method is effective for monitoring breast cancer?

Research has shown that using the investigational drug [18F]FMISO with PET/MRI scans can track changes in certain breast tumors known as HER2-positive. In this trial, participants will divide into two cohorts: one receiving Herceptin monotherapy and the other receiving combination therapy including Herceptin. Studies have found that this imaging technique can monitor how these tumors respond to trastuzumab (Herceptin). Specifically, one study showed that this method is practical and promising for breast cancer patients. The imaging provides important details about the tumor, such as its size and activity level, helping doctors understand how the cancer responds to treatment. ^{1 2 3 4 6}

Who Is on the Research Team?

Jonathan McConathy, MD, PhD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with advanced HER2+ breast cancer, eligible for neoadjuvant therapy and not yet started treatment. Participants must have a tumor identifiable by imaging and an expected lifespan over one year. Pregnant or breastfeeding women, those with MRI contraindications like certain metal implants, tattoos, or weighing over 350 lbs., are excluded.

Inclusion Criteria

I have stage II-III HER2+ breast cancer and haven't started treatment yet.

You must have at least one tumor that can be measured and is larger than 1 cm in diameter.

My breast cancer is HER2 positive based on lab tests.

Exclusion Criteria

Lactating, known or suspected pregnancy. Women with child-bearing potential must have a negative serum β-hCG pregnancy test within 48 hours or a negative urine β-hCG pregnancy test within 48 hours of each PET imaging study

I cannot use a specific dye (ProHance) for MRI scans due to health reasons.

Contraindication for MRI study (e.g. non-removable metal implants or certain tattoos)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Imaging Visits

Participants undergo PET/MRI imaging sessions to monitor the effect of trastuzumab on chemotherapy

Varies by cohort

3-4 visits (in-person)

Follow-up

Participants are monitored for changes in imaging metrics and clinical response

5 years

Every 6 months (medical record review)

What Are the Treatments Tested in This Trial?

Interventions

• [18F]FMISO

Trial Overview [18F]FMISO PET/MRI imaging is being tested to monitor the response of HER2+ breast cancer to trastuzumab (Herceptin) combined with chemotherapy. This study aims to improve future treatments but won't alter current patient care plans.

How Is the Trial Designed?

Group I: Herceptin monotherapy cohort Experimental Treatment 1 Intervention

Herceptin monotherapy cohort. Locally advanced HER2+ breast cancer patients receiving neoadjuvant Herceptin monotherapy prior to combination therapy will undergo three contrast-enhanced \[18F\]FMISO PET/MRI scans. Each imaging session will be identical. Imaging session one will be after diagnosis and before beginning monotherapy. Imaging session two will be within 10 days prior to beginning combination therapy with targeted HER2 agents. Imaging session three will be within 10 days prior to beginning the second round of combination therapy with targeted HER2 agents.

Group II: Combination therapy cohort Experimental Treatment 1 Intervention

Locally advanced HER2+ breast cancer patients that receiving neoadjuvant combination therapy including Herceptin will undergo two contrast-enhanced \[18F\]FMISO PET/MRI imaging. Imaging session one will be after diagnosis and before beginning combination therapy. Imaging session two will be within 10 days prior to beginning the second round of combination therapy with targeted HER2 agents.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

The study demonstrated that 18F-FES PET imaging is effective for early prediction of tumor response to endocrine therapy in estrogen receptor-positive breast cancer, showing a strong correlation with tumor growth and ER levels.

In contrast, the other PET tracers, 18F-FDG and 18F-FMISO, did not correlate well with treatment response, highlighting the unique efficacy of 18F-FES in monitoring therapy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of 18F-FES, 18F-FDG, and 18F-FMISO PET Imaging Probes for Early Prediction and Monitoring of Response to Endocrine Therapy in a Mouse Xenograft Model of ER-Positive Breast Cancer. He, S., Wang, M., Yang, Z., et al.[2018]

Molecular imaging techniques, such as (18)F-FDG PET/CT and scintimammography, provide functional information that enhances the diagnosis, staging, and monitoring of breast cancer compared to traditional imaging methods.

The development of new radiopharmaceuticals allows for better visualization of specific biomarkers related to breast cancer, which can lead to more targeted therapies and improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nuclear Medicine in diagnosis of breast cancer]. Iakovou, IP., Giannoula, E.[2016]

Positron emission tomography (PET) is becoming an important tool in both the clinical management and research of breast cancer, helping to visualize and understand the disease better.

Current applications primarily use the radiotracer (18)F-fluorodeoxyglucose (FDG), but there is ongoing research into other radiopharmaceuticals that could provide more insights into breast cancer biology and may soon be tested in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and future use of positron emission tomography (PET) in breast cancer. Mankoff, DA., Eubank, WB.[2018]

The study successfully synthesized two radiotracers, [18F]FMISO and [18F]PM-PBB3, using a new method called 18F-fluoroalkylation, which produced sufficient radioactivity for clinical applications.

Both radiotracers demonstrated appropriate radiochemical yields, with [18F]FMISO achieving a yield of 26% and [18F]PM-PBB3 achieving a yield of 16%, indicating their potential effectiveness for imaging hypoxia and tau pathology in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automated radiosynthesis of two 18F-labeled tracers containing 3-fluoro-2-hydroxypropyl moiety, [18F]FMISO and [18F]PM-PBB3, via [18F]epifluorohydrin. Ohkubo, T., Kurihara, Y., Ogawa, M., et al.[2021]

The second phase 3 clinical trial of Fluorine-18 Flurpiridaz PET myocardial perfusion imaging (MPI) aims to assess its effectiveness in diagnosing significant coronary artery disease (CAD) in patients suspected of having the condition, using invasive coronary angiography as the gold standard.

This study will also compare the diagnostic efficacy of F-18 Flurpiridaz PET MPI to the traditional Tc-99m-labeled SPECT MPI, particularly in specific subgroups such as females, obese patients, and diabetics, providing a comprehensive evaluation of its performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing myocardial perfusion in suspected coronary artery disease: rationale and design of the second phase 3, open-label multi-center study of flurpiridaz (F-18) injection for positron emission tomography (PET) imaging. Bourque, JM., Hanson, CA., Agostini, D., et al.[2022]

Positron emission tomography/computed tomography (PET/CT) is a rapidly growing imaging technique in cancer management, but the commonly used radiotracer [(18)F]fluorodeoxyglucose (FDG) is not specific for malignant disease, highlighting the need for more tumor-specific PET radiopharmaceuticals.

Over the past 15 years, various alternative (18)F-labeled radiotracers have been developed and evaluated, which may provide better characterization of tumor biology, emphasizing the importance of regulatory compliance and safety in their clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

(18)F-labeled positron emission tomographic radiopharmaceuticals in oncology: an overview of radiochemistry and mechanisms of tumor localization. Vallabhajosula, S.[2022]

This pilot study involving nine breast cancer patients demonstrated that sequential multiparametric 18[F]FDG/[18F]FMISO PET-MRI can effectively assess tumor heterogeneity and correlate with important prognostic indicators, such as tumor proliferation and recurrence risk.

Strong correlations were found between PET imaging parameters and clinical outcomes, particularly with disease-specific death and metastasis, suggesting that this imaging technique could enhance precision medicine approaches in breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential [18F]FDG-[18F]FMISO PET and Multiparametric MRI at 3T for Insights into Breast Cancer Heterogeneity and Correlation with Patient Outcomes: First Clinical Experience. Andrzejewski, P., Wengert, G., Helbich, TH., et al.[2020]

The fourth synthesis approach for [18F]FMISO, using [18F]epifluorohydrin, achieved a reliable production with a radiochemical yield of 7-12% and a high specific activity of over 400 Ci/mmol in just 1.5 hours.

Preliminary PET studies indicate that [18F]FMISO could be a promising tracer for identifying ischemic but viable heart tissue, suggesting its potential clinical utility in cardiac imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No-carrier-added synthesis of 3-[18F]fluoro-1-(2-nitro-1-imidazolyl)-2-propanol. A potential PET agent for detecting hypoxic but viable tissues. Hwang, DR., Dence, CS., Bonasera, TA., et al.[2019]

Fluorodeoxyglucose (FDG) PET imaging is crucial for diagnosing, staging, and managing breast cancer, with its sensitivity varying based on tumor size and histology.

FDG PET can significantly alter staging and treatment plans, especially in cases of recurrent disease, and it also provides valuable prognostic and predictive information about the cancer's progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET Imaging of Breast Cancer: Role in Patient Management. Lebron, L., Greenspan, D., Pandit-Taskar, N.[2016]

In a study of 14 patients with head and neck cancer, FMISO-PET imaging showed a significant decrease in tumor hypoxia during radiotherapy, as indicated by reduced standard uptake values (SUV) and tumor-muscle ratios (TMR).

The majority of patients (11 out of 14) exhibited a change in their hypoxia status towards lower levels after receiving 30Gy of radiation, suggesting that radiotherapy may induce reoxygenation of tumors, which could potentially improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypoxia-imaging with (18)F-Misonidazole and PET: changes of kinetics during radiotherapy of head-and-neck cancer. Eschmann, SM., Paulsen, F., Bedeshem, C., et al.[2022]

PET imaging, particularly using FDG PET/CT, is crucial for diagnosing and managing breast cancer, although it has specific clinical indications and limitations.

The review also discusses the emerging role of PET/MRI and the newly approved radiopharmaceutical FES for imaging estrogen receptors, which could enhance the understanding of breast cancer biology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET Imaging for Breast Cancer. Fowler, AM., Cho, SY.[2021]

PET-MRI is a promising hybrid imaging technology that combines metabolic and functional data from PET with detailed anatomical information from MRI, enhancing the early detection and clinical staging of breast cancer.

Ongoing research into targeted radiopharmaceuticals and automated analysis tools is expected to improve the effectiveness of PET-MRI in diagnosing, staging, and monitoring treatment responses in breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical advances in PET-MRI for breast cancer. Fowler, AM., Strigel, RM.[2023]

PET/MRI, introduced in 2010, combines high-resolution MRI with metabolic PET data, showing high diagnostic value for whole-body cancer staging, particularly in breast cancer.

This imaging modality improves detection of distant metastases and lymph node involvement, potentially allowing for less invasive treatments and reducing the need for extensive surgeries like mastectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Role of PET/MR in Breast Cancer? Bruckmann, NM., Morawitz, J., Fendler, WP., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04332588

Monitoring HER2+ Breast Cancer Neoadjuvant Treatment ... The purpose of the study is to see if using an investigational drug called [18F]FMISO with PET/MRI imaging can help monitor and predict the effect of ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6341235/

Sequential [18F]FDG-[18F]FMISO PET and Multiparametric ... We demonstrated the feasibility and potential of multiparametric [18F]FDG/[18F]FMISO PET-MRI in breast cancer patients. Our pilot study showed ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-00341

[18F]FMISO-PET/MRI Scan for the Monitoring of Treatment ... This phase I trial studies the usefulness of [18F]FMISO-PET/MRI in monitoring treatment response in patients with HER2+ stage II-III breast cancer who are ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12345643/

Multiparametric Analysis of PET and Quantitative MRI for ... This study explores how combined PET/MRI imaging can track early biological changes within HER2-positive breast tumors treated with trastuzumab, ...

5. withpower.com withpower.com/trial/phase-1-breast-neoplasms-11-2021-eef33

Advanced PET/MRI Imaging for Breast Cancer The research suggests that using [18F]FMISO in combination with PET/MRI imaging can provide important information about breast cancer, such as tumor ...

6. breast-cancer-research.biomedcentral.com breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-018-0970-6

Intracellular hypoxia measured by 18 F-fluoromisonidazole ... FMISO-PET/CT is useful for assessing the prognosis of patients with breast cancer, but it should be stratified by ER status.