PET Scan Predictors for HER2+ Breast Cancer Treatment Response

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must be taking: Trastuzumab, Pertuzumab

Disqualifiers: Metastatic disease, Concurrent malignancy, others

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: 9

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to predict treatment effectiveness for women with HER2 positive breast cancer that has spread locally. It uses a special PET scan to forecast the effectiveness of two cancer treatments, trastuzumab (also known as Herceptin, Trazimera, Herzuma, or Ontruzant) and pertuzumab (also known as Perjeta), before surgery. Women with HER2 positive breast cancer, whose tumors are at least 2 cm in size and who have not received previous HER2-targeted treatments, might be suitable candidates for this study. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the trial involves specific cancer treatments, it's best to discuss your current medications with the trial team to ensure there are no conflicts.

What prior data suggests that copper Cu64-DOTA-trastuzumab PET is safe for predicting treatment response in HER2+ breast cancer?

Research shows that the treatments used in this study, trastuzumab and pertuzumab, are generally safe and well-tolerated by patients. Trastuzumab has been widely used and studied in HER2-positive breast cancer, significantly reducing cancer recurrence and death rates. Safety data indicate it is well-tolerated, with manageable side effects.

Pertuzumab, often used with trastuzumab, also has a good safety record. Studies have shown that adding pertuzumab can lower the risk of disease progression. Most patients handle it well, though some may experience mild to moderate side effects.

The copper Cu 64-DOTA-trastuzumab PET scan is a newer diagnostic tool. Early results suggest it is safe, with no major safety concerns reported. This imaging method helps doctors predict how well trastuzumab and pertuzumab will work before surgery.

In this phase II trial, the treatments' known safety records and the diagnostic tool's early safety data suggest they are generally well-tolerated by patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the combination of trastuzumab and pertuzumab for HER2+ breast cancer because it adds a novel layer of precision with PET scan imaging. Unlike the standard of care, which typically involves these drugs without imaging, this approach incorporates copper Cu 64-DOTA-trastuzumab, allowing doctors to visualize and predict how well the cancer will respond to treatment in real-time. This could potentially enable more personalized and timely adjustments to therapy, providing a clearer picture of treatment effectiveness much earlier than traditional methods.

What evidence suggests that copper Cu64-DOTA-trastuzumab PET is effective for predicting treatment response in HER2+ breast cancer?

Research has shown that trastuzumab significantly lowers the chances of HER2-positive breast cancer recurrence and reduces the risk of death from this cancer type. It effectively improves survival rates for patients with both early-stage and advanced cancer that has spread. In this trial, participants will receive trastuzumab and pertuzumab, which together offer a strong defense against HER2-positive breast cancer. Adding pertuzumab to the treatment helps patients live longer without disease progression and increases overall survival. Additionally, the trial will explore using special PET scans with copper Cu 64-DOTA-trastuzumab to predict patient response to these treatments, aiming to tailor and improve care. ^{1 2 3 4 5}

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 breast cancer that's locally advanced. They must have a tumor at least 2cm big or similarly sized lymph nodes, confirmed by imaging tests. Participants need normal heart function and haven't had prior HER2 treatments. Pregnant women can't join, nor those who've received treatment for the current cancer or have another active cancer.

Inclusion Criteria

My primary tumor or lymph nodes are at least 2cm large as confirmed by imaging.

I am a woman with lab-confirmed HER2 positive breast cancer.

I have not had treatments specifically targeting HER2.

Exclusion Criteria

I am not a candidate for the standard HER2 cancer treatment.

My cancer has not spread to distant parts of my body.

I have cancer other than non-melanoma skin cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

PET Imaging and Initial Treatment

Patients receive trastuzumab and copper Cu 64-DOTA-trastuzumab followed by PET scans to predict treatment response

1 week

2 visits (in-person)

Neoadjuvant Treatment

Patients receive trastuzumab and pertuzumab every 21 days for 6 cycles

18 weeks

6 visits (in-person)

Surgery

Patients undergo surgery after completion of neoadjuvant treatment

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Copper Cu 64-DOTA-Trastuzumab
• Pertuzumab
• Trastuzumab

Trial Overview The study is testing if a PET scan using Cu64-DOTA-trastuzumab can predict how well patients respond to pre-surgery treatment with trastuzumab and pertuzumab. It involves diagnostic procedures before receiving six cycles of combined therapy with these drugs plus chemotherapy.

How Is the Trial Designed?

Group I: Treatment (trastuzumab, copper Cu 64-DOTA-trastuzumab PET) Experimental Treatment 6 Interventions

Patients receive trastuzumab IV over 15 minutes immediately before receiving copper Cu 64-DOTA-trastuzumab IV on day 0. Patients undergo PET scans at 18-24 and 42-48 hours, on day 1 and day 2. Within 4 days after completion of PET scans, patients receive trastuzumab IV over 30-90 minutes weekly or every 3 weeks and pertuzumab IV over 30-60 minutes. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo surgery after 6 cycles of trastuzumab and pertuzumab.

Pertuzumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Perjeta for:

• Early breast cancer
• Metastatic breast cancer

Approved in United States as Perjeta for:

• Early breast cancer
• Metastatic breast cancer

Approved in Canada as Perjeta for:

• Early breast cancer
• Metastatic breast cancer

Approved in Japan as Perjeta for:

• Early breast cancer
• Metastatic breast cancer

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

Pertuzumab, a new monoclonal antibody targeting HER2, has shown improved patient outcomes in clinical trials for early-stage and metastatic HER2-positive breast cancer, especially when used in combination with chemotherapy and trastuzumab.

The review highlights that while trastuzumab has improved survival for HER2-positive breast cancer, there is still a need for better treatment options, which pertuzumab aims to address, particularly for patients who continue to relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab in human epidermal growth-factor receptor 2-positive breast cancer: clinical and economic considerations. Lamond, NW., Younis, T.[2021]

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 ... 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 of ...

4. jnm.snmjournals.org jnm.snmjournals.org/content/60/1/26

Development of 64Cu-NOTA-Trastuzumab for HER2 ... Conclusion: 64Cu-NOTA-trastuzumab was effectively targeted to the HER2-expressing tumor in vitro and in vivo, and it exhibited a relatively low ...

5. ejnmmires.springeropen.com ejnmmires.springeropen.com/articles/10.1186/s13550-021-00746-1

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