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

Trial Summary

What is the purpose of this trial?

Our goal is to investigate the use of 89Zr-trastuzumab as a HER2 imaging agent to determine which patients are likely to respond to targeted HER2 agents as single agent therapy. We are proposing to perform a pilot study with goals of demonstrating the feasibility of imaging breast cancer patients with 89Zr-trastuzumab-PET/MRI, evaluating the relationship between tumor 89Zr-trastuzumab uptake and in vitro positivity of HER2, assessing the relationship between 89Zr-trastuzumab uptake and response to HER2 therapy.

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 data supports the effectiveness of the drug 89Zr-Trastuzumab for breast cancer?

Research shows that 89Zr-Trastuzumab can help visualize and measure the uptake of the drug in HER2-positive breast cancer lesions using PET scans, which may improve the accuracy of treatment response evaluation. This imaging technique has been shown to correlate with target expression levels, suggesting it could help predict how well a patient might respond to treatment. ^{1 2 3 4 5}

Is 89Zr-Trastuzumab PET Imaging safe for humans?

Initial clinical trials with 89Zr-Trastuzumab PET imaging have shown that it can be used to visualize and quantify tumor uptake in patients with HER2-positive breast cancer, but specific data on safety or side effects in humans is not detailed in the available studies. Further research is needed to fully understand its safety profile. ^{2 3 4 5 6}

How is 89Zr-Trastuzumab PET Imaging different from other breast cancer treatments?

89Zr-Trastuzumab PET Imaging is unique because it uses a radioactive tracer, Zirconium-89, attached to the trastuzumab antibody to visualize and measure the uptake of the drug in HER2-positive breast cancer lesions. This imaging technique helps predict how well a patient is responding to treatment, potentially allowing for more personalized and effective therapy decisions. ^{1 2 3 4 5}

Research Team

Suzanne E Lapi, PhD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

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 18 years old or older.

I am fully active or can carry out light work.

Exclusion Criteria

Inability to provide informed consent

I cannot stay still for imaging tests.

Pregnancy

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

(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 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]

References

1. Switzerland 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. [2023]

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

Biodistribution of 89Zr-trastuzumab and PET imaging of HER2-positive lesions in patients with metastatic breast cancer. [2022]

3. Switzerland 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? [2022]

4. Iran pubmed.ncbi.nlm.nih.gov

Development and evaluation of 89Zr-trastuzumab for clinical applications. [2023]

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

89Zr-Chloride Can Be Used for Immuno-PET Radiochemistry Without Loss of Antigen Reactivity In Vivo. [2020]

6. Germany pubmed.ncbi.nlm.nih.gov

Macrocycle-Based Hydroxamate Ligands for Complexation and Immunoconjugation of 89Zirconium for Positron Emission Tomography (PET) Imaging. [2019]