Copper Cu 64-DOTA-Trastuzumab PET for HER2 Positive Breast Cancer

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: City of Hope Medical Center

Must not be taking: Trastuzumab

Disqualifiers: Concurrent malignancy, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 12

Duration: Up to 1 year

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial uses a special scan to track a drug in patients with advanced HER2 positive breast cancer. The scan helps predict if the treatment will be effective by showing how much of the drug reaches the tumors. Patients are then treated with a specific cancer drug.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have received trastuzumab within 6 weeks before the PET scan.

What data supports the effectiveness of the drug Copper Cu 64-DOTA-Trastuzumab PET for HER2 Positive Breast Cancer?

The drug ado-trastuzumab emtansine, a component of the treatment, has been shown to improve survival rates in patients with HER2-positive early breast cancer, as demonstrated in the KATHERINE trial. Additionally, Copper Cu 64-DOTA-Trastuzumab PET imaging has been effective in detecting HER2-positive tumors, which helps in assessing the appropriate use of anti-HER2 therapies. ^{1 2 3 4 5}

Is Copper Cu 64-DOTA-Trastuzumab safe for humans?

Trastuzumab emtansine, a similar treatment, has been shown to be generally safe in humans, with common side effects including fatigue, nausea, and increased liver enzymes, which are manageable. Serious side effects like cardiotoxicity (heart damage) were not reported, and any blood-related issues were reversible. ^{2 3 6 7 8}

How is the drug ado-trastuzumab emtansine unique for treating HER2-positive breast cancer?

Ado-trastuzumab emtansine is unique because it combines trastuzumab, which targets HER2-positive cancer cells, with emtansine, a powerful chemotherapy drug, allowing it to deliver chemotherapy directly to cancer cells while minimizing damage to healthy cells. This targeted approach improves effectiveness and reduces some of the side effects typically associated with chemotherapy. ^{2 4 8 9 10}

Research Team

Joanne Mortimer

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for women with HER2 positive metastatic breast cancer that has spread to the lung, liver, soft-tissue or bone. Participants must be able to consent, have a performance status of 0-2, a recent biopsy confirming HER2 positivity without subsequent HER2 therapy, normal heart function and at least one large enough metastasis. Pregnant women and those who've had trastuzumab within 6 weeks are excluded.

Inclusion Criteria

I am able to care for myself and perform daily activities.

My heart pumps well, with an ejection fraction of 50% or higher.

I haven't taken trastuzumab in the last 6 weeks.

Exclusion Criteria

Inability to provide informed consent

I have another type of cancer besides skin cancer.

My cancer has not spread to areas larger than 20 mm.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Diagnostic

Patients undergo whole body fludeoxyglucose F 18 PET/CT and receive trastuzumab IV before copper Cu 64-DOTA-trastuzumab IV, followed by PET scans at 24 and 48 hours

1 week

3 visits (in-person)

Treatment

Patients receive ado-trastuzumab emtansine IV every 3 weeks until complete response or disease progression

Up to 1 year

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Every 6 weeks (in-person)

Treatment Details

Interventions

• Ado-Trastuzumab Emtansine
• Copper Cu 64-DOTA-Trastuzumab
• Trastuzumab

Trial Overview The study tests if Copper Cu 64-DOTA-trastuzumab PET scans can predict the effectiveness of ado-trastuzumab emtansine treatment in patients. It involves attaching a radioactive substance to chemotherapy drug trastuzumab and using PET scans to track its movement in the body.

Participant Groups

Group I: Diagnostic (copper Cu 64-DOTA-trastuzumab PET) Experimental Treatment 7 Interventions

Patients undergo whole body fludeoxyglucose F 18 PET/CT. Patients then receive trastuzumab IV over 15 minutes immediately before receiving copper Cu 64-DOTA-trastuzumab IV and then undergo PET scans at 24 and 48 hours. Patients then receive ado-trastuzumab emtansine IV every 3 weeks until complete response or disease progression at the discretion of the treating oncologist. Patients undergo restaging by whole body fludeoxyglucose F 18 PET/CT every 6 weeks after initiation of treatment until disease progression.

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

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]

Ado-trastuzumab emtansine (KADCYLA) received FDA approval for treating HER2-positive early breast cancer patients with residual disease after chemotherapy, showing an impressive 88.3% event-free survival rate at 3 years compared to 77.0% for trastuzumab.

The treatment was associated with common side effects such as fatigue and nausea, but it represents a significant advancement as the first approved therapy for patients with residual disease post-neoadjuvant treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Ado-Trastuzumab Emtansine for the Adjuvant Treatment of HER2-positive Early Breast Cancer. Wedam, S., Fashoyin-Aje, L., Gao, X., 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]

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]

Trastuzumab emtansine is an effective treatment for HER2-positive breast cancer, showing significant improvements in overall survival compared to lapatinib plus capecitabine in a phase III study, with a maximum tolerated dose established at 3.6 mg/kg.

The treatment has a favorable safety profile, with minimal systemic toxicities and a low incidence of adverse events typically associated with chemotherapy, such as cardiotoxicity, making it a promising option for patients with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The success story of trastuzumab emtansine, a targeted therapy in HER2-positive breast cancer. Diéras, V., Bachelot, T.[2021]

Trastuzumab emtansine (Kadcyla®) is effective in reducing the risk of invasive disease recurrence or death by 50% compared to trastuzumab in patients with HER2-positive early breast cancer after neoadjuvant treatment, as shown in the KATHERINE trial.

The safety profile of trastuzumab emtansine is consistent with previous findings, with more adverse events reported compared to trastuzumab, leading to its recommendation as a preferred treatment option in updated guidelines for high-risk breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Emtansine: A Review of Its Adjuvant Use in Residual Invasive HER2-Positive Early Breast Cancer. Lyseng-Williamson, KA.[2022]

References

1. 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]

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

FDA Approval Summary: Ado-Trastuzumab Emtansine for the Adjuvant Treatment of HER2-positive Early Breast Cancer. [2021]

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

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

4. England pubmed.ncbi.nlm.nih.gov

Ado-trastuzumab emtansine for the treatment of human epidermal growth factor receptor 2-positive metastatic breast cancer. [2019]

5. 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]

6. France pubmed.ncbi.nlm.nih.gov

The success story of trastuzumab emtansine, a targeted therapy in HER2-positive breast cancer. [2021]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Trastuzumab Emtansine: A Review of Its Adjuvant Use in Residual Invasive HER2-Positive Early Breast Cancer. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Prognostic factors of ado-trastuzumab emtansine treatment in patients with metastatic HER-2 positive breast cancer. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine: determining its role in management of HER2+ breast cancer. [2019]

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

Ado-Trastuzumab Emtansine for Patients With HER2-Mutant Lung Cancers: Results From a Phase II Basket Trial. [2023]