89Zr-Trastuzumab PET Imaging for Breast Cancer

Overseen By Sebastian Eady, BS

Age: 18+

Sex: Female

Trial Phase: Phase < 1

Sponsor: University of Alabama at Birmingham

Must be taking: Anti-HER2 agents

Disqualifiers: Pregnancy, Metal implants, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 week

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to evaluate the effectiveness of certain breast cancer treatments. It employs a special imaging technique with 89Zr-trastuzumab, a radiolabeled antibody, to determine if a person's cancer might respond to treatments targeting HER2, a protein influencing cancer growth. Only individuals with HER2-positive breast cancer who can undergo radiation or specific drug treatments qualify. Participants receive a small dose of the drug through an IV, followed by imaging a few days later. The study aims to enhance how doctors select the best treatment for each patient. As an Early Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to experience this innovative approach.

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 might be best to discuss this with the trial coordinators or your doctor.

What prior data suggests that 89Zr-trastuzumab is safe for imaging breast cancer patients?

Research shows that [89Zr]-trastuzumab is generally safe for humans when used for imaging. Studies have found that patients with HER2-positive breast cancer tolerate it well. One study noted that the liver receives the most radiation, but this remains within safe limits. Imaging typically occurs at least 4 days after injection, allowing the body time to process the tracer. Overall, these studies consider the treatment safe, with no major side effects reported. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for breast cancer, which often include chemotherapy, hormone therapy, and targeted therapies like Herceptin (trastuzumab), [89Zr]-Df-Trastuzumab offers a new approach by combining a radioactive tracer with trastuzumab. What makes [89Zr]-Df-Trastuzumab unique is its ability to allow for precise PET/MRI imaging, potentially providing a clearer picture of how the cancer is responding to treatment. This could mean more personalized and effective treatment plans. Researchers are particularly excited about this method because it could lead to earlier and more accurate assessments of how well a treatment is working, thereby improving patient outcomes.

What evidence suggests that 89Zr-trastuzumab is effective for imaging breast cancer?

Research has shown that 89Zr-trastuzumab, which participants in this trial will receive, holds promise for imaging HER2-positive breast cancer. This imaging could help doctors predict a patient's response to certain treatments. Studies have found that this agent can effectively detect cancer spread to areas such as the liver, lungs, bones, and brain. Early results suggest a link between the amount of 89Zr-trastuzumab absorbed by tumors and the patient's response to HER2-targeted therapies. This means the imaging could assist doctors in selecting the best treatment options for individuals with this type of breast cancer. Although researchers continue to study this method, the initial results are encouraging. ^{2 3 5 6 7}

Who Is on the Research Team?

Suzanne E Lapi, PhD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for adults over 18 with HER2 positive breast cancer, meeting specific diagnostic criteria. They should be in good physical condition (ECOG status of 0 or 1) and have a heart ejection fraction above 50%. It's not suitable for those who can't undergo MRI, are pregnant, unable to consent, cannot stay still for imaging, or weigh more than 350 lbs.

Inclusion Criteria

I am eligible for treatment that targets the HER2 protein in my cancer.

I am fully active or can carry out light work.

My breast cancer is HER2 positive according to specific guidelines.

Exclusion Criteria

Inability to provide informed consent

I cannot stay still for imaging tests.

Pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an intravenous dose of [89Zr]-Df-Trastuzumab, followed by PET/MRI imaging 5-6 days post-injection

1 week

1 visit (in-person) for injection, 1 visit (in-person) for imaging

Follow-up

Participants are monitored for safety and effectiveness after imaging

4 weeks

Long-term follow-up

Participants are monitored for long-term outcomes related to HER2 therapy response

24 months

What Are the Treatments Tested in This Trial?

Interventions

• [89Zr]-Df-Trastuzumab

Trial Overview

The study tests if PET/MRI imaging using [89Zr]-Df-Trastuzumab can predict the effectiveness of targeted HER2 therapy in breast cancer patients. The goal is to see if the uptake of this tracer correlates with laboratory measures of HER2 and response to treatment.

How Is the Trial Designed?

Group I: [89Zr]-Df-Trastuzumab Experimental Treatment 2 Interventions

\[89Zr\]-Df-Trastuzumab \[89Zr\]-Df-Trastuzumab will be administered intravenously. The administered dose will be 2 millicurie (mCi) at the time of injection. The amount of injected drug is 5 mg of Trastuzumab. 5-6 days post injection the patients will undergo PET/MRI imaging.

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

(89)Zr-immuno-PET is a promising imaging technique that can visualize and quantify the distribution of monoclonal antibodies (mAbs) in tumors, helping to predict their efficacy and toxicity based on initial clinical trials.

Initial studies have shown that (89)Zr-immuno-PET correlates with target expression levels in tumors, indicating its potential as a predictive biomarker for personalized treatment, particularly in HER2-positive breast cancer with trastuzumab-emtansine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immuno-Positron Emission Tomography with Zirconium-89-Labeled Monoclonal Antibodies in Oncology: What Can We Learn from Initial Clinical Trials? Jauw, YW., Menke-van der Houven van Oordt, CW., Hoekstra, OS., et al.[2022]

The [89Zr]Zr-Trastuzumab radioimmunoconjugate demonstrated high purity and stability, with over 70% binding to HER2-positive BT474 cells, indicating its potential effectiveness for targeting HER2+ tumors.

In preclinical studies, [89Zr]Zr-Trastuzumab showed significant uptake in tumor sites and effectively delineated HER2+ metastasis in a patient with breast cancer, suggesting its utility in improving diagnosis and treatment planning for HER2-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and evaluation of 89Zr-trastuzumab for clinical applications. Mohammadpour-Ghazi, F., Yousefnia, H., Divband, G., et al.[2023]

The study explored the use of 89Zr-trastuzumab PET/CT imaging for evaluating the response to neoadjuvant systemic therapy in HER2-positive breast cancer patients, finding it feasible for identifying primary tumors and metastatic lymph nodes.

While qualitative assessment of PET/CT did not outperform standard MRI, the quantitative measures showed promise for more accurately evaluating treatment response, particularly in distinguishing between complete and partial responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

89Zr-Trastuzumab PET/CT Imaging of HER2-Positive Breast Cancer for Predicting Pathological Complete Response after Neoadjuvant Systemic Therapy: A Feasibility Study. Linders, DGJ., Deken, MM., van Dam, MA., et al.[2023]

The study involving 14 patients with HER2-positive metastatic breast cancer found that administering 50 mg of (89)Zr-trastuzumab to trastuzumab-naive patients and 10 mg to those already on trastuzumab was optimal for PET imaging, with the best assessment occurring 4-5 days post-injection.

(89)Zr-trastuzumab effectively allowed for the visualization and quantification of HER2-positive lesions, revealing both known and previously undetected tumors, indicating its potential utility in improving cancer diagnosis and treatment monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biodistribution of 89Zr-trastuzumab and PET imaging of HER2-positive lesions in patients with metastatic breast cancer. Dijkers, EC., Oude Munnink, TH., Kosterink, JG., et al.[2022]

The use of 89ZrCl4 for radiolabeling monoclonal antibodies like trastuzumab and cetuximab resulted in high specific activity and maintained over 95% purity for at least 3 days when formulated with L-methionine, indicating effective preparation for immuno-PET imaging.

89Zr-DFO-trastuzumab demonstrated sustained reactivity toward its target antigen in PET/CT imaging of lung cancer models, suggesting its potential utility in precision medicine for cancer diagnostics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

89Zr-Chloride Can Be Used for Immuno-PET Radiochemistry Without Loss of Antigen Reactivity In Vivo. Pandya, DN., Bhatt, NB., Almaguel, F., et al.[2020]

The novel chelator 89Zr-L4 demonstrated stability similar to the established 89Zr-DFO complex in biological conditions, indicating its potential for safe use in medical applications.

When conjugated to trastuzumab, the bifunctional chelator 89Zr-L5 showed excellent tumor targeting with a high tumor-to-blood ratio, suggesting it could be an effective tool for imaging and treating HER2-positive cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Macrocycle-Based Hydroxamate Ligands for Complexation and Immunoconjugation of 89Zirconium for Positron Emission Tomography (PET) Imaging. Boros, E., Holland, JP., Kenton, N., et al.[2019]

Citations

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The primary aim of this clinical trial was to evaluate the feasibility of using 89Zr-trastuzumab PET (for HER2-positive breast cancer) or 89Zr-bevacizumab PET [ ...

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Development and evaluation of 89Zr-trastuzumab for ...

The results also showed the ability of [89Zr]Zr-Trastuzumab immune-PET imaging to detect metastatic liver, lung, bone, and even brain lesions in patients with ...

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pubmed.ncbi.nlm.nih.gov

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[ 89 Zr]trastuzumab was safe and optimally imaged at least 4 days post-injection. The liver was the dose-limiting organ.

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[89Zr]Trastuzumab: Evaluation of Radiation Dosimetry ...

Purpose The purpose of the present study is to evaluate safety, human radiation dosimetry, and optimal imaging time of [89Zr]trastuzumab in patients with ...