Investigational Scan for Breast Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: City of Hope Medical Center

Must be taking: Trastuzumab deruxtecan

Disqualifiers: Immediate intervention, Lung disease, Corneal disease, Cardiac issues

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This clinical trial examines an investigational scan (64Cu-DOTA-trastuzumab positron emission tomography \[PET\]/magnetic resonance imaging \[MRI\]) in imaging patients with HER2+ breast cancer that has spread to the brain (brain metastasis). Diagnostic procedures, such as 64Cu-DOTA-trastuzumab PET/MRI, may help find HER2+ breast cancer that has spread to the brain and determine whether cancer in the brain takes up trastuzumab, which may predict for response to trastuzumab deruxtecan (the standard of care chemotherapy).

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the trial involves imaging and not a new treatment, it's possible that you may not need to stop them. Please consult with the trial coordinators for specific guidance.

What data supports the effectiveness of the investigational scan for breast cancer treatment using 64Cu-DOTA-Trastuzumab PET/MRI?

Research shows that 64Cu-DOTA-Trastuzumab PET imaging can effectively detect HER2-positive tumors in breast cancer patients, indicating its potential to help identify appropriate candidates for anti-HER2 therapies. Studies in mice and patients with HER2-positive cancers have demonstrated high uptake of the tracer in tumors, suggesting it can accurately assess HER2 expression and guide treatment decisions. ^{1 2 3 4 5}

Is 64Cu-DOTA-Trastuzumab safe for humans?

A study on 64Cu-DOTA-Trastuzumab PET imaging in patients with HER2-positive breast cancer aimed to determine its safety, suggesting that there is some safety data available for this treatment in humans. ^{1 2 6 7 8}

How does the investigational scan for breast cancer differ from other treatments?

The investigational scan for breast cancer uses a radiolabeled version of trastuzumab, a drug that targets HER2, to non-invasively image HER2 expression in tumors. This approach is unique because it allows for the visualization of HER2 status throughout the body, potentially optimizing the use of anti-HER2 therapies by identifying which patients are most likely to benefit from them. ^{1 2 3 4 7}

Research Team

Joanne E Mortimer, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for adults over 18 with HER2+ breast cancer that has spread to the brain. They must have a certain level of hemoglobin, kidney function, heart function, and blood cell counts. Patients already planning treatment with fam-trastuzumab deruxtecan can join. Those with serious recent heart issues or lung disease needing steroids cannot participate.

Inclusion Criteria

I am scheduled to receive fam-trastuzumab deruxtecan treatment.

Your absolute neutrophil count is higher than 1.5 x 10^9 per liter.

I am a woman with HER2 positive breast cancer that has spread to my brain.

Exclusion Criteria

I have a lung condition treated with steroids but it's not caused by an infection.

I have a serious eye condition affecting the cornea.

I haven't had a heart attack or serious heart issues in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive trastuzumab IV on day 0, followed by 64Cu-DOTA-trastuzumab IV and PET/MRI scan on day 1. Repeat brain MRI every 6 weeks for 24 weeks, then every 9 weeks until disease progression. Trastuzumab deruxtecan IV every 21 days in the absence of disease progression or unacceptable toxicity.

24 weeks

Multiple visits for MRI and IV administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• 64Cu-DOTA-Trastuzumab PET/MRI
• Trastuzumab
• Trastuzumab Deruxtecan

Trial Overview The study is testing a new scan combining PET and MRI using a tracer called 64Cu-DOTA-Trastuzumab to see if it's better at detecting HER2+ breast cancer in the brain and predicting response to standard chemotherapy (trastuzumab deruxtecan).

Participant Groups

Group I: Treatment ( 64Cu-DOTA-trastuzumab PET/MRI) Experimental Treatment 5 Interventions

Patients receive trastuzumab IV over 15 minutes on day 0. Patients then receive 64Cu-DOTA-trastuzumab IV and then undergo PET/MRI scan on day 1. Patients undergo repeat brain MRI every 6 weeks for 24 weeks and then every 9 weeks until disease progression. Patients then receive trastuzumab deruxtecan IV every 21 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a pilot study involving 8 patients with gastric adenocarcinoma, the use of 64 Cu-DOTA-trastuzumab for PET imaging showed limited toxicity and some uptake in HER2+ lesions, but it was not effective in distinguishing between tumor and background tissue.

The study indicates that the 5 mg dose of 64 Cu-DOTA-trastuzumab was insufficient for effective imaging of HER2+ gastric cancer, suggesting that future research should focus on optimizing dosage and timing for better identification of HER2 overexpressing tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of HER2 targeted 64 Cu-DOTA-tagged PET imaging in gastric cancer patients. Hernandez, MC., Yazaki, P., Mortimer, JE., et al.[2023]

Trastuzumab, when labeled with (64)Cu and used in PET imaging, specifically targets and accumulates in non-small cell lung carcinoma (NSCLC) tumors that overexpress the Her2/neu gene, demonstrating its potential as a non-invasive imaging tool.

The study showed that (64)Cu-DOTA-trastuzumab had significantly higher uptake in Her2/neu positive tumors compared to negative ones, indicating its effectiveness in identifying patients who may benefit from trastuzumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging and biodistribution of Her2/neu expression in non-small cell lung cancer xenografts with Cu-labeled trastuzumab PET. Paudyal, P., Paudyal, B., Hanaoka, H., et al.[2019]

The study evaluated (64)Cu-DOTA-trastuzumab PET/CT in 8 women with HER2-positive metastatic breast cancer, showing high sensitivity for detecting tumors (77% to 93%) and effective imaging of HER2 expression without observed toxicities.

A 45-mg predose of trastuzumab significantly reduced liver uptake of the radiotracer, enhancing the imaging of tumors, indicating that this method could help personalize anti-HER2 therapies for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional imaging of human epidermal growth factor receptor 2-positive metastatic breast cancer using (64)Cu-DOTA-trastuzumab PET. Mortimer, JE., Bading, JR., Colcher, DM., et al.[2022]

The study found that the uptake of 64Cu-DOTA-trastuzumab in metastatic breast cancer patients is strongly associated with HER2 status, indicating that this imaging technique can effectively reflect the binding of trastuzumab to HER2-positive tumors.

Among the 18 patients studied, those with HER2-positive tumors showed significantly higher radiolabel uptake compared to HER2-negative patients, suggesting that 64Cu-DOTA-trastuzumab PET/CT could help tailor trastuzumab treatments based on individual HER2 status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor Uptake of 64Cu-DOTA-Trastuzumab in Patients with Metastatic Breast Cancer. Mortimer, JE., Bading, JR., Park, JM., et al.[2021]

The study successfully optimized the labeling of trastuzumab with copper-64, achieving high radiochemical purity (>97%) for both DOTA-trastuzumab and NODAGA-trastuzumab, which are important for accurate imaging in HER2-positive breast cancer.

In a preliminary mouse model, both labeled tracers demonstrated significant tumor uptake (3-9% ID/g), indicating their potential effectiveness for imaging HER2-expressing tumors in cancer diagnostics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[(64) Cu]-labelled trastuzumab: optimisation of labelling by DOTA and NODAGA conjugation and initial evaluation in mice. Schjoeth-Eskesen, C., Nielsen, CH., Heissel, S., et al.[2021]

PET/CT imaging using 64Cu-NOTA-pertuzumab F(ab')2 effectively detected changes in HER2 expression in ovarian cancer models, indicating its potential for monitoring treatment response to trastuzumab.

This method resulted in a significantly lower radiation dose to the body (0.015 mSv/MBq) compared to the previously used 111In-labeled pertuzumab, making it a safer imaging option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and preclinical studies of 64Cu-NOTA-pertuzumab F(ab')2 for imaging changes in tumor HER2 expression associated with response to trastuzumab by PET/CT. Lam, K., Chan, C., Reilly, RM.[2019]

The study involving 16 women with breast cancer showed that 68Ga-DOTA-F(ab')2-trastuzumab is well tolerated, with a half-life of approximately 3.6 hours and a low radiation dose to the kidneys, indicating its safety for use in patients.

Tumor targeting was observed in 4 out of 8 patients with HER2-positive breast cancer, suggesting that this imaging agent may effectively assess HER2 expression and monitor treatment response, although further studies with larger doses and better-defined patient groups are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of 68Ga-DOTA-F(ab')2-trastuzumab in patients with breast cancer. Beylergil, V., Morris, PG., Smith-Jones, PM., et al.[2021]

The study demonstrated that (64)Cu-DOTA-trastuzumab PET imaging is safe and effective for identifying HER2-positive tumors in breast cancer patients, with optimal imaging occurring 48 hours post-injection.

The radiation exposure from (64)Cu-DOTA-trastuzumab PET is comparable to that of conventional (18)F-FDG PET, and the imaging successfully detected brain metastases and primary tumors, indicating its potential for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

64Cu-DOTA-trastuzumab PET imaging in patients with HER2-positive breast cancer. Tamura, K., Kurihara, H., Yonemori, K., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Pilot study of HER2 targeted 64 Cu-DOTA-tagged PET imaging in gastric cancer patients. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Imaging and biodistribution of Her2/neu expression in non-small cell lung cancer xenografts with Cu-labeled trastuzumab PET. [2019]

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

Functional imaging of human epidermal growth factor receptor 2-positive metastatic breast cancer using (64)Cu-DOTA-trastuzumab PET. [2022]

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

Tumor Uptake of 64Cu-DOTA-Trastuzumab in Patients with Metastatic Breast Cancer. [2021]

5. England pubmed.ncbi.nlm.nih.gov

[(64) Cu]-labelled trastuzumab: optimisation of labelling by DOTA and NODAGA conjugation and initial evaluation in mice. [2021]

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

Development and preclinical studies of 64Cu-NOTA-pertuzumab F(ab')2 for imaging changes in tumor HER2 expression associated with response to trastuzumab by PET/CT. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Pilot study of 68Ga-DOTA-F(ab')2-trastuzumab in patients with breast cancer. [2021]

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

64Cu-DOTA-trastuzumab PET imaging in patients with HER2-positive breast cancer. [2022]