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

Trial Summary

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 data supports the effectiveness of the drug 89Zr-trastuzumab for HER2-PET imaging in breast cancer?

Research shows that 89Zr-trastuzumab PET imaging can help identify HER2-positive breast cancer lesions, even in cases where standard methods struggle to determine HER2 status. This imaging technique can also predict how well patients respond to pre-surgery treatments, potentially reducing the need for surgery. ^{1 2 3 4 5}

Is 89Zr-trastuzumab safe for use in humans?

Studies have shown that 89Zr-trastuzumab is generally safe for use in humans, with no toxicities reported in trials involving patients with HER2-positive breast cancer. ^{3 5 6 7 8}

How is HER2-PET Imaging for Breast Cancer different from other treatments?

HER2-PET Imaging for Breast Cancer is unique because it uses a special imaging technique with a tracer called 89Zr-trastuzumab to detect HER2-positive cancer cells, even when standard tests can't determine HER2 status. This approach helps in making more informed treatment decisions and can identify HER2-positive metastases in patients who initially had HER2-negative breast cancer. ^{2 3 4 5 9}

What is the purpose of this trial?

A strategy to target the oncogenic receptor HER2 using a version of the anti-HER2 therapeutic antibody trastuzumab coupled to desferrioxamine (DFO) and radiolabeled with zirconium-89 (\[89Zr\]-DFO-trastuzumab) has been successfully evaluated in our group in preclinical settings. Clinical studies by other groups in recent years have shown the potential of targeting HER2+ lesions with \[89Zr\]-DFO-trastuzumab in patients with HER2+ cancers. We now want to establish the diagnostic potential of a protocol adding \[89Zr\]-DFO-trastuzumab PET imaging to FDG PET already used in the clinic for the detection of HER2-expressing cancers, including low expression levels considered until now as HER2-negative (HER2-low, IHC score 1+ and 2+ without FISH amplification of the HER2 locus). The HER2-low status has recently gained relevance thanks to large studies showing the efficacy of immunotherapy combined with drugs such as Enhertu (trastuzumab-deruxtecan), while trastuzumab alone was traditionally only effective for HER2+ cancers (IHC score 2+/FISH+, or 3+). In particular, we aim to develop a method to assess whole-body intertumoral heterogeneity in HER2 expression in order to detect cases with heterogeneous diseases and thus better stage patients and guide the optimal choice of personalized and targeted treatment to use. More specifically, the project aims to image with \[89Zr\]-DFO-trastuzumab PET patients with cancer, particularly breast cancer, but also esophageal, gastric, ovarian, endometrial and lung cancer, and whose primary tumor status is HER2-low.

Research Team

Éric E Turcotte, MD, FRCPC

Principal Investigator

Université de Sherbrooke

Eligibility Criteria

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

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

Treatment Details

Interventions

• 89Zr-trastuzumab

Participant Groups

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+

Findings from Research

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]

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 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]

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 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 [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]

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]

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]

References

1. 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]

2. 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]

3. United States 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. [2018]

4. Germany 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. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Evaluation of [89Zr]trastuzumab-PET/CT in differentiating HER2-positive from HER2-negative breast cancer. [2022]

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

[89Zr]Trastuzumab: Evaluation of Radiation Dosimetry, Safety, and Optimal Imaging Parameters in Women with HER2-Positive Breast Cancer. [2022]

7. Iran pubmed.ncbi.nlm.nih.gov

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

8. United States 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. [2019]

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

Monitoring afatinib treatment in HER2-positive gastric cancer with 18F-FDG and 89Zr-trastuzumab PET. [2021]