HER2-PET Imaging for Breast Cancer

Overseen By Esteban Espinosa-Bentancourt

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Centre de recherche du Centre hospitalier universitaire de Sherbrooke

Disqualifiers: Pregnancy, Hepatic disorders, Renal disorders, others

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

Compensation: Varies

Number of Visits: 2

Duration: 1 week

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to develop a new imaging method to better detect and understand HER2-low breast cancer. By using a special PET scan with 89Zr-trastuzumab (a radiolabeled antibody), researchers seek to observe how cancer expresses HER2, a protein that can influence treatment decisions. The goal is to enhance how doctors stage the cancer and choose targeted treatments. Patients with metastatic HER2-low breast cancer who can lie on their back for at least 30 minutes may be suitable for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to benefit from 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's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this protocol is safe for HER2-low cancer patients?

Research shows that the treatment called 89Zr-trastuzumab has been tested in patients with HER2-positive breast cancer. In these studies, most participants tolerated the treatment well, with few experiencing serious problems. The main goal was to measure radiation absorption and determine the optimal timing for imaging.

When patients received 89Zr-trastuzumab, side effects were usually mild, and severe reactions were uncommon. This suggests the treatment is relatively safe. However, since this trial is in the early stages, researchers are still assessing its safety for patients with HER2-low cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard imaging methods for breast cancer, which typically focus on anatomical changes, 89Zr-trastuzumab PET/CT imaging targets the HER2 protein directly. This approach allows for more precise visualization of HER2-low breast cancer, potentially identifying tumors that might not be detected with conventional scans. Researchers are excited about this technique because it could enable more personalized treatment plans by accurately determining HER2 status, providing a clearer picture of how the cancer is behaving in the body.

What evidence suggests that this protocol is effective for imaging HER2-low breast cancer?

Research has shown that a special imaging technique called 89Zr-trastuzumab PET/CT is promising for detecting cancers with the HER2 protein, even in small amounts. This trial will use 89Zr-trastuzumab PET/CT imaging specifically for patients with HER2-low breast cancer. Studies have found that this method can accurately identify HER2-positive tumors and small areas of metastasis. For patients with low HER2 levels, this imaging helps doctors better understand the cancer stage and plan treatments. It provides detailed images of cancer spread, particularly in breast cancer cases, enabling doctors to create more personalized treatment plans by knowing the exact HER2 status throughout the body. ^{2 3 6 7 8}

Who Is on the Research Team?

Éric E Turcotte, MD, FRCPC

Principal Investigator

Université de Sherbrooke

Are You a Good Fit for This Trial?

Inclusion Criteria

My breast cancer is HER2-low and has spread.

Written informed consent

I can lie on my back for at least 30 minutes without discomfort.

Exclusion Criteria

Known hypersensitivity or allergy to trastuzumab, desferrioxamine, or any constituents of 89Zr-trastuzumab

I do not have significant liver conditions that could affect drug processing.

Pregnancy or concomitant breastfeeding

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 trastuzumab followed by 89Zr-trastuzumab, with PET/CT imaging conducted 3-6 days later

1 week

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 89Zr-trastuzumab

How Is the Trial Designed?

Group I: 89Zr-trastuzumab PET/CT imaging of HER2-low patients Experimental Treatment 1 Intervention

Following their inform consent, HER2-low breast cancer patients will be invited to come to our research center twice. The first time patients will receive an intravenous dose of 10-50mg trastuzumab, followed by a 0.5 MBq/kg (max 60 MBq) dose of 89Zr-trastuzumab. Patients will come back for a second visit 3-6 days later to get their PET/CT imaging examination. Images will be evaluated by two PET-trained physicians, and analysed by an imaging scientist.

Who Is Running the Clinical Trial?

Centre de recherche du Centre hospitalier universitaire de Sherbrooke

Lead Sponsor

Trials

64

Recruited

33,600+

Université de Sherbrooke

Collaborator

Trials

317

Recruited

79,300+

Published Research Related to This Trial

The study involving 12 women with HER2-positive breast cancer demonstrated that [89Zr]trastuzumab is safe for use, with no adverse effects reported during the imaging process.

Optimal imaging for [89Zr]trastuzumab occurs around 5 days post-injection, providing high-quality images and effective tumor detection, while the liver was identified as the dose-limiting organ in terms of radiation exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[89Zr]Trastuzumab: Evaluation of Radiation Dosimetry, Safety, and Optimal Imaging Parameters in Women with HER2-Positive Breast Cancer. Laforest, R., Lapi, SE., Oyama, R., et al.[2022]

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 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]

This first-in-human study involving 6 patients with HER2-positive metastatic breast cancer demonstrated that 89Zr-pertuzumab PET/CT is safe, with no reported toxicities during the trial.

The imaging technique effectively visualized HER2-positive metastases, confirming its potential for assessing HER2 status in lesions that are difficult to biopsy, and it accurately identified HER2-positive brain metastases in one patient, which was later confirmed by surgical resection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Human Epidermal Growth Factor Receptor 2-Targeted Imaging Using 89Zr-Pertuzumab PET/CT: Dosimetry and Clinical Application in Patients with Breast Cancer. Ulaner, GA., Lyashchenko, SK., Riedl, C., et al.[2019]

Imaging with Zr-trastuzumab PET/CT can successfully identify unsuspected HER2-positive metastases in some patients with HER2-negative primary breast cancer, as demonstrated in a study of 11 patients where 1 out of 4 suspicious lesions was confirmed HER2-positive.

However, the study also revealed a challenge with false-positive results, as 3 out of 4 suspicious lesions were found to be HER2-negative, indicating that while Zr-trastuzumab PET/CT is promising, its specificity needs to be improved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

89Zr-Trastuzumab PET/CT for Detection of Human Epidermal Growth Factor Receptor 2-Positive Metastases in Patients With Human Epidermal Growth Factor Receptor 2-Negative Primary Breast Cancer. Ulaner, GA., Hyman, DM., Lyashchenko, SK., et al.[2018]

In a study involving 50 women with breast cancer, [89Zr]trastuzumab-PET/CT successfully identified HER2-positive tumors in 88.2% of cases and HER2-negative tumors in 93.7%, indicating its potential as a non-invasive diagnostic tool.

The study found that while overall tumor uptake was not significantly different between HER2-positive and HER2-negative patients, excluding liver lesions revealed a significant difference, suggesting that [89Zr]trastuzumab can effectively differentiate HER2 status in most tumors without the need for invasive tissue sampling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of [89Zr]trastuzumab-PET/CT in differentiating HER2-positive from HER2-negative breast cancer. Dehdashti, F., Wu, N., Bose, R., et al.[2022]

The imaging agent (89)Zr-trastuzumab effectively identified HER2-positive gastric cancer and was able to monitor the effects of the drug afatinib, showing a significant decrease in its uptake after treatment, indicating a response to therapy.

Afatinib demonstrated antitumor activity in HER2-positive gastric cancer, leading to tumor reduction and downregulation of HER2 and EGFR within 24 hours of treatment, with effects sustained over 21 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring afatinib treatment in HER2-positive gastric cancer with 18F-FDG and 89Zr-trastuzumab PET. Janjigian, YY., Viola-Villegas, N., Holland, JP., et al.[2021]

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]

In a feasibility trial involving 20 patients with unclear HER2 status in breast cancer, 89Zr-trastuzumab PET imaging significantly aided clinical decision-making, supporting treatment adjustments in 15 out of 20 cases.

The PET scan improved physicians' understanding of the disease in 18 patients and altered treatment plans for 8 patients, demonstrating its potential as a valuable tool when standard methods fail to clarify HER2 status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

89Zr-trastuzumab PET supports clinical decision making in breast cancer patients, when HER2 status cannot be determined by standard work up. Bensch, F., Brouwers, AH., Lub-de Hooge, MN., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10605041/

89Zr-Trastuzumab PET/CT Imaging of HER2-Positive ... Our results suggest that quantitative assessment of 89Zr-trastuzumab PET/CT has potential for a more accurate response evaluation of the primary tumor after NAT ...

2. jnm.snmjournals.org jnm.snmjournals.org/content/early/2025/06/05/jnumed.124.268931

Quantitative [89Zr]Zr-Trastuzumab PET and Diffusion The goal of this study was to present quantitative imaging metrics from [89Zr]Zr-trastuzumab PET and simultaneous DW-MRI to characterize HER2- ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06732336?term=HER2%20imaging&viewType=Table&rank=1

HER2-PET Imaging in HER2-low Breast Cancers Evaluate 89Zr-trastuzumab PET imaging in a HER2 -low breast cancer patient cohort, Patients (n=40) will be injected with a dose of 89Zr-trastuzumab, then ...

4. ascopubs.org ascopubs.org/doi/10.1200/jco.2007.25.18_suppl.3508

Characterization of 89Zr-trastuzumab for clinical HER2 ... MicroPET imaging showed excellent tumor uptake and could easily detect metastases with a size approximating the spatial resolution of the ...

5. pubs.rsna.org pubs.rsna.org/doi/abs/10.1148/radiol.2020192828

Identification of HER2-Positive Metastases in Patients with ... HER2-targeted imaging with zirconium 89–pertuzumab PET/CT was successful in detecting HER2-positive metastases in women with HER2-negative primary breast ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5096950/

[89Zr]Trastuzumab: Evaluation of Radiation Dosimetry, Safety ... Purpose. To evaluate safety, human radiation dosimetry and optimal imaging time of [89Zr]trastuzumab in patients with HER2-positive breast cancer.

7. link.springer.com link.springer.com/article/10.1007/s00259-018-4099-8

89 Zr-trastuzumab PET supports clinical decision making in ... Zr-trastuzumab PET supports clinical decision making in breast cancer patients, when HER2 status cannot be determined by standard work up.

8. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/559542

HER2-PET Imaging in HER2-low Breast Cancers HER2-PET Imaging Using 89Zr-trastuzumab in Low HER2-expressing (HER2-low) Breast Cancers. Estimated trial completion date. Mar 31, 2026.