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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates a new method to determine if a specific breast cancer treatment might benefit patients with HER2-positive breast cancer that has metastasized. It employs a special PET scan to track a drug linked with a small amount of radioactive material (Copper Cu 64-DOTA-Trastuzumab). This process helps doctors see the drug's distribution and assess if the patient might benefit from ado-trastuzumab emtansine. Women with metastatic HER2-positive breast cancer that has spread to the lungs, liver, soft tissue, or bone may be suitable candidates for this trial. As an unphased trial, this study provides patients the chance to contribute to innovative research that could influence future treatment options.

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 prior data suggests that this diagnostic method is safe for predicting treatment response in HER2 positive breast cancer?

Research has shown that copper Cu 64-DOTA-trastuzumab PET imaging is generally safe. Studies have found that patients tolerate the procedure well, with no major safety issues reported. Participants in these trials did not experience significant side effects.

The FDA has already approved ado-trastuzumab emtansine for certain breast cancer cases, indicating its safety is well understood and acceptable. However, like any treatment, it may cause side effects such as tiredness, nausea, or muscle pain, though serious side effects are less common.

Overall, both the imaging and the treatment have demonstrated a strong safety record based on available research. ^{1 2 3 4 5}

Why are researchers excited about this trial?

The treatment Copper Cu 64-DOTA-Trastuzumab PET is unique because it combines a diagnostic imaging technique with a targeted therapy approach for HER2 positive breast cancer. This treatment uses a radioactive copper tracer to enhance PET scans, providing detailed images of cancer spread, which helps in tailoring personalized treatment plans. Additionally, it leverages trastuzumab, a monoclonal antibody, to specifically target and bind to HER2 receptors on cancer cells, potentially improving the precision and effectiveness of therapy. Researchers are excited about this combination because it offers a dual benefit of accurate diagnosis and targeted treatment, potentially leading to better outcomes for patients.

What evidence suggests that copper Cu 64-DOTA-trastuzumab PET is effective for predicting treatment response in HER2 positive breast cancer?

Research has shown that a special type of scan, called a copper Cu 64-DOTA-trastuzumab PET scan, can effectively image breast cancer in patients with HER2-positive tumors. In this trial, participants will undergo this scan to help predict their response to treatment with ado-trastuzumab emtansine. Studies have found that these tumors absorb the tracer well, making this scan a promising way to assess treatment potential. This imaging technique allows doctors to see where the drug travels in the body, helping to identify patients likely to benefit from the treatment. The use of 64Cu-trastuzumab has proven effective in similar situations, suggesting it could reliably guide treatment decisions in advanced HER2-positive breast cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Joanne Mortimer

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02226276

NCT02226276 | Copper Cu 64-DOTA-Trastuzumab PET in ... Copper Cu 64-DOTA-Trastuzumab PET in Predicting Response to Treatment With Ado-Trastuzumab Emtansine in Patients With Metastatic HER2 Positive Breast Cancer.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9185799/

Copper-64 trastuzumab PET imaging: A reproducibility study Recent work has reported successful imaging of breast cancer using 64Cu-trastuzumab (19, 20), which has a 12.7-hour half-life. The use of 64Cu may enable ...

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

Towards integration of 64Cu-DOTA-trastuzumab PET-CT ... We present the results of utilizing a biophysical mathematical model to predict tumor response for two HER2 + breast cancer patients treated ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7818354/

A preliminary clinical trial to evaluate 64Cu-NOTA ... In our study, HER2-positive tumors showed a high 64Cu-NOTA-Trastuzumab uptake, whereas HER2-negative tumors did not. Adding to the previous preclinical results ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02827877

Study Details | Cu64-DOTA-trastuzumab PET and Markers ... Active, not recruiting. Cu64-DOTA-trastuzumab PET and Markers Predicting Response to Neoadjuvant Trastuzumab + Pertuzum in HER2+ Breast Cancer.

6. jnm.snmjournals.org jnm.snmjournals.org/content/55/1/23

Functional Imaging of Human Epidermal Growth Factor ... The purpose of this study was to evaluate PET/CT of 64Cu-DOTA-trastuzumab for detecting and measuring tumor uptake of trastuzumab in patients ...

7. withpower.com withpower.com/trial/phase-neoplasms-second-primary-2015-6dc8c

Copper Cu 64-DOTA-Trastuzumab PET for HER2 Positive ... 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 ...