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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a special scan to detect breast cancer that has spread to the brain and assess its response to a specific type of chemotherapy. The scan combines PET, which shows how body tissues work, and MRI, which provides detailed images of organs and tissues. Women with HER2-positive breast cancer that has spread to their brain and who plan to undergo specific chemotherapy might be suitable for this trial. The scan used is called 64Cu-DOTA-Trastuzumab PET/MRI. As a Phase 4 trial, this research involves an FDA-approved treatment and aims to understand how it can benefit more patients.

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 is the safety track record for the investigational scan 64Cu-DOTA-trastuzumab PET/MRI?

Research shows that using 64Cu-DOTA-trastuzumab PET imaging is both feasible and safe for patients. This method helps identify HER2-positive breast cancer areas, even if they have metastasized to the brain. Studies suggest it can be performed safely without requiring an overnight hospital stay.

Trastuzumab, approved by the FDA for treating HER2-positive breast cancer, is generally well-tolerated, though some may experience side effects like fever, chills, or nausea.

Trastuzumab deruxtecan, another FDA-approved treatment for HER2-positive breast cancer, is effective but may cause side effects such as low blood cell counts or lung issues. Its approval indicates a well-understood safety profile.

Overall, research indicates these treatments are generally well-tolerated, with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the investigational scan for breast cancer because it combines advanced imaging with targeted therapy. Unlike standard treatments that may involve separate imaging and therapy sessions, this method uses 64Cu-DOTA-Trastuzumab, a radiolabeled antibody, to deliver precise imaging through PET/MRI and assess the effectiveness of trastuzumab treatment in real-time. This approach allows for a more personalized treatment plan by tracking how the cancer responds over time. Additionally, the use of trastuzumab deruxtecan, an antibody-drug conjugate, offers a novel way to deliver chemotherapy directly to cancer cells, potentially reducing side effects and improving outcomes. This innovative combination could lead to earlier detection of treatment response and more effective management of breast cancer.

What evidence suggests that this investigational scan is effective for imaging HER2+ breast cancer brain metastasis?

Research has shown that the 64Cu-DOTA-trastuzumab PET/MRI scan, which participants in this trial will undergo, can effectively detect HER2-positive breast cancer that has spread to the brain. This scan uses a special tracer that binds to the HER2 protein on cancer cells, making them visible. Studies indicate that this method can accurately locate cancerous areas, aiding doctors in determining if the cancer will respond to trastuzumab deruxtecan chemotherapy, also part of the treatment plan in this trial. The scan's ability to map cancer spread is particularly useful in planning treatment for cancer that has reached the brain. Overall, these findings support the scan's potential role in guiding treatment decisions for patients with HER2-positive breast cancer. ^{2 5 6 7 8}

Who Is on the Research Team?

Joanne E Mortimer, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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 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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9364339/

Use of 64Cu-DOTA-Trastuzumab PET to Predict Response ... We report the results of a pilot study testing whether pretreatment 64 Cu-DOTA-trastuzumab PET/CT can predict benefit from T-DM1 for HER2-positive metastatic ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05376878?term=trastuzumab&viewType=Table&rank=10

An Investigational Scan (64Cu-DOTA-Trastuzumab PET ... 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 ...

3. nature.com nature.com/articles/s41598-020-77397-0

Towards integration of 64Cu-DOTA-trastuzumab PET-CT ... The 64Cu-DT-PET data is used to define a normalized map of the distribution of the targeted anti-HER2 therapy trastuzumab based on the dosage ...

4. jnm.snmjournals.org jnm.snmjournals.org/content/54/11/1869

64Cu-DOTA-Trastuzumab PET Imaging in Patients with ... 64 Cu-DOTA-trastuzumab PET is feasible for the identification of HER2-positive lesions in patients with primary and metastatic breast cancer.

5. ascopubs.org ascopubs.org/doi/10.1200/jco.2014.32.15_suppl.618

Correlation of 64Cu DOTA-trastuzumab positron emission ... We have determined that administering trastuzumab (45 mg) prior to 64Cu-DOTA-trastuzumab sharply reduces liver uptake of the radiotracer.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24029656/

64Cu-DOTA-trastuzumab PET imaging in patients with ... Conclusion: The findings of this study indicated that (64)Cu-DOTA-trastuzumab PET is feasible for the identification of HER2-positive lesions ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05376878

NCT05376878 | An Investigational Scan (64Cu-DOTA- ... 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 ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4385241/

64Cu-DOTA-trastuzumab PET imaging and HER2 specificity ... Conclusions. Cu-DOTA-trastuzumab PET imaging was safe and feasible for outpatients. This technique can be used to visualize metastatic brain ...