Stopping HER-2 Directed Therapy for Breast Cancer

(Free-HER Trial)

Overseen By Elisa Krill Jackson, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Miami

Must be taking: Anti-HER-2 therapy

Must not be taking: Investigational drugs

Disqualifiers: Uncontrolled metastatic disease, Secondary cancer, others

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether patients with HER-2 positive metastatic breast cancer can discontinue ongoing anti-HER-2 treatments, such as Trastuzumab (Herceptin), while maintaining complete remission, meaning no signs of cancer on scans. Researchers will closely monitor participants to determine if they remain cancer-free without treatment and for how long. Suitable candidates have had stable disease for at least three years on their current anti-HER-2 therapy and show no signs of cancer in blood tests. As an unphased trial, this study offers a unique opportunity to contribute to understanding long-term remission without ongoing treatment.

Will I have to stop taking my current medications?

Yes, you will need to stop taking your current anti-HER-2 therapy, but you will be closely monitored during the trial.

What prior data suggests that discontinuing anti-HER-2 maintenance treatment is safe?

Research shows that treatments like Herceptin and similar anti-HER-2 medications are generally well-tolerated by patients. Studies have found that biosimilar trastuzumab, which resembles Herceptin, has a comparable safety record. Patients using these treatments experience side effects similar to those of the original drug.

Earlier studies examined the main safety concern by assessing deaths within 30 days after the last dose of treatment. Results have consistently shown these treatments to be safe for most people across different settings.

Overall, anti-HER-2 treatments have been tested in large groups of patients with HER2-positive breast cancer, and these studies support their safety. Patients should always discuss any concerns about side effects or safety with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores the possibility of discontinuing anti-HER-2 maintenance treatments in breast cancer patients who are in complete radiological remission. Unlike the typical ongoing administration of anti-HER-2 therapies like trastuzumab and pertuzumab, this trial investigates if patients can maintain remission without continuous treatment. By using ctDNA monitoring in addition to routine imaging and blood work, the trial aims to determine if this approach can effectively indicate remission status, potentially reducing the need for long-term drug therapy and its associated side effects.

What evidence suggests that discontinuing anti-HER-2 maintenance treatment might be effective for maintaining remission in breast cancer?

Research has shown that treatments like trastuzumab are effective for HER2-positive breast cancer. Adding trastuzumab to chemotherapy can reduce the chance of cancer recurrence by about one-third and decrease the risk of death from breast cancer by a similar amount. For those with more advanced cancer, combining trastuzumab with other drugs can result in nearly 19 months without cancer progression. Overall, these treatments have significantly improved outcomes for patients with this type of breast cancer. In this trial, researchers will monitor participants in the anti-HER-2 group to determine if discontinuing maintenance of anti-HER-2 treatments, along with ctDNA monitoring and routine assessments, will maintain complete radiological remission. ^{6 7 8 9 10}

Who Is on the Research Team?

Elisa Krill Jackson, MD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

This trial is for adults over 18 with HER-2 positive metastatic breast cancer in complete radiological remission. They must have been on anti-HER-2 therapy for at least 3 years, have no evidence of circulating tumor DNA, and be able to consent. Those with stable treated brain metastasis may join, but not those with recent other cancers or uncontrolled disease.

Inclusion Criteria

My scans show no signs of cancer currently.

I have Stage IV breast cancer that is HER-2 positive.

My brain metastasis has been stable for at least 3 years after treatment.

Exclusion Criteria

I have or am receiving treatment for another cancer besides non-melanoma skin cancer or in situ cancer in the last 2 years.

History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or that makes participation in the trial to be not in the best interest of the patient in the opinion of the Investigator

Use of investigational drugs ≤ 28 days prior to study enrollment and during the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Monitoring

Participants are monitored with ctDNA, radiologic imaging, and routine blood work after discontinuing anti-HER-2 treatments to assess maintenance of complete radiological remission

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment discontinuation

Up to 72 months

What Are the Treatments Tested in This Trial?

Interventions

• Anti-HER-2 Maintenance Treatment

Trial Overview The study tests if stopping maintenance anti-HER-2 treatments like Herceptin in long-term survivors leads to continued remission. Participants will be closely monitored through imaging and blood work to track their cancer status after discontinuing the treatment.

How Is the Trial Designed?

Group I: anti-HER-2 Group Experimental Treatment 1 Intervention

Participants in this group will be monitored to see if patients discontinuing maintenance of anti-HER-2 treatments with ctDNA monitoring in addition to radiologic imaging and routine blood work will stay in complete radiological remission. Participants will be in this group for up to 3 years.

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

Published Research Related to This Trial

Re-treatment with Herceptin (trastuzumab) in patients with recurrent HER2-positive breast cancer showed a median progression-free survival of 12.7 months and an overall survival of 31.6 months, indicating its effectiveness in this setting.

The study found no new safety concerns related to cardiac health during Herceptin re-treatment, suggesting that it is well-tolerated even in patients with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resumption of Trastuzumab in Patients With Disease Recurrence After (Neo-) Adjuvant Anti-HER2-therapy in Patients With HER2-positive Breast Cancer. Hanker, LC., FÖrster, F., SchrÖder, J., et al.[2020]

Trastuzumab (Herceptin) is generally well-tolerated in cancer therapy, showing mild-to-moderate adverse effects primarily after the first dose, with a low incidence of severe side effects.

However, there is a significant risk of cardiac toxicity, particularly in patients who have previously received anthracycline chemotherapy, which was higher than expected and highlights the need for careful patient management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability in patients receiving trastuzumab with or without chemotherapy. Gianni, L.[2020]

HER2-positive breast cancer, which historically had a poor prognosis, can now be effectively treated with a variety of anti-HER2 therapies, significantly improving patient survival rates.

Newly developed treatments, including trastuzumab deruxtecan and trastuzumab emtansine, along with ongoing clinical trials, are expanding options for patients with advanced HER2-positive breast cancer, raising important questions about the best treatment sequences and combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-HER2 Drugs for the Treatment of Advanced HER2 Positive Breast Cancer. Stanowicka-Grada, M., Senkus, E.[2023]

Trastuzumab (Herceptin) is a safe and effective treatment for patients with metastatic breast cancer that overexpresses the HER2 gene, showing response rates of 11% to 23% in various phase II studies involving heavily pretreated and previously untreated patients.

The treatment is associated with a low incidence of serious side effects, primarily cardiac dysfunction syndrome in less than 5% of patients, and does not cause common chemotherapy side effects like hair loss or low blood cell counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trials of single-agent trastuzumab (Herceptin). Baselga, J.[2015]

An 81-year-old patient with HER2-positive metastatic breast cancer achieved complete remission after 21 months of trastuzumab maintenance therapy and has remained in remission for 6 years, highlighting the potential for long-term effectiveness of trastuzumab in this patient population.

Current evidence suggests that trastuzumab maintenance therapy should not be interrupted, as there is no clear safety data indicating that it can be safely stopped without risking relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged complete remission of metastatic HER2-positive breast cancer after continuous trastuzumab treatment: a case report and review of the literature. Ihnenfeld Arciénega, I., Imesch, P., Fink, D., et al.[2022]

A patient with HER2-positive metastatic breast cancer achieved long-term stable disease for over 4 years while receiving combined maintenance therapy with trastuzumab and lapatinib after initial treatments.

This case suggests that using a combination of HER2-targeted agents may enhance the effectiveness of maintenance therapy, potentially leading to better outcomes for patients with aggressive forms of breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual HER2 Suppression with Lapatinib plus Trastuzumab for Metastatic Inflammatory Breast Cancer: A Case Report of Prolonged Stable Disease. Ogawa, L., Lindquist, D.[2022]

In a study of 215 patients with metastatic HER2 positive breast cancer, trastuzumab treatment resulted in a median progression-free survival of 12 months, with 48% of patients remaining in remission beyond one year.

Trastuzumab was well tolerated, with only 13% of patients experiencing any grade of left ventricular dysfunction, indicating that cardiac safety is maintained even after prolonged use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcome of HER2 positive metastatic breast cancer patients treated with first-line trastuzumab. Yeo, B., Kotsori, K., Mohammed, K., et al.[2015]

Trastuzumab has significantly improved outcomes for patients with HER2-positive metastatic breast cancer (MBC), with some patients achieving prolonged remission, including two who remained in remission for over a year after stopping the treatment.

There is currently no established optimal duration for trastuzumab maintenance therapy in patients with prolonged remission, highlighting the need for further research to identify predictive markers for better personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duration of trastuzumab in patients with HER2-positive metastatic breast cancer in prolonged remission. Haq, R., Gulasingam, P.[2022]

Retreatment with trastuzumab significantly prolongs time to progression (TTP) and overall survival (OS) in patients with HER2-positive metastatic breast cancer, based on a meta-analysis of 2,409 patients from 10 studies.

The study found that continuing trastuzumab treatment does not increase the risk of cardiac events or central nervous system metastasis, indicating it is a safe option for patients who have progressed on previous trastuzumab regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab treatment after progression in HER2-positive metastatic breast cancer following relapse of trastuzumab-based regimens: a meta-analysis. Han, Y., Wang, J., Liu, W., et al.[2020]

Trastuzumab (Herceptin) has been shown to significantly improve outcomes in HER-2-positive breast cancer, reducing the risk of recurrence by about 50% and the risk of death by nearly 30%, based on evidence from five large phase III adjuvant trials.

Herceptin is now approved for use in combination with chemotherapy for the adjuvant treatment of HER-2-positive breast cancer, marking a significant advancement in the management of this previously challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Trastuzumab (Herceptin) in the adjuvant treatment of HER-2-positive early breast cancer]. Láng, I., Hitre, E.[2015]

Trastuzumab (Herceptin) is an effective first-line treatment for metastatic breast cancer patients with HER2 overexpression/amplification, improving both disease-free and overall survival when used alone or with chemotherapy.

Despite its benefits, there are ongoing uncertainties regarding the optimal use of trastuzumab, including its safety during long-term treatment, the effectiveness of continuing treatment after disease progression, and its combination with hormone therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perspective of trastuzumab treatment. Iwata, H.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8324484/

Trastuzumab for early-stage, HER2-positive breast cancer Adding trastuzumab to chemotherapy for patients with early-stage, HER2-positive breast cancer reduces recurrence of and mortality from breast cancer by a third, ...

2. nature.com nature.com/articles/s41523-024-00652-4

The survival benefit of adjuvant trastuzumab with or without ... Cumulatively, they found that the addition of trastuzumab improved OS and reduced the 3-year breast cancer recurrence risk by nearly half.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666379124002672

Emerging treatments in HER2-positive advanced breast ... The addition of pertuzumab to trastuzumab and taxane demonstrated a median progression-free survival (PFS) of 18.7 months in untreated, advanced ...

4. academic.oup.com academic.oup.com/oncolo/article/28/10/e867/7243566

Real-World Impact of Adjuvant Anti-HER2 Treatment on ... Anti-HER2-targeted therapies have dramatically improved the outcome of patients with HER2+ localized breast cancer. However, it is documented ...

5. esmoopen.com esmoopen.com/article/S2059-7029(23)00843-8/fulltext

Management of patients with HER2-positive metastatic ... In this scenario, T-DXd has shown to portend better survival outcomes compared to T-DM1, while leaving a large unsought area of unmet medical ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38534957/

Comparative Effectiveness and Safety of Trastuzumab ... Biosimilar trastuzumab demonstrated similar safety and effectiveness to Herceptin. The findings can help improve confidence in and use of biosimilars.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10969053/

Comparative Effectiveness and Safety of Trastuzumab ... Outcomes. The primary safety outcome was death within 30 days of the last dose of neoadjuvant/adjuvant trastuzumab for HER2+ breast cancer.

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e13023

Efficacy and safety of trastuzumab deruxtecan in HER2+ ... Our study supports the efficacy and safety of T-DXd in India in a real-world clinical setting with results being consistent across published literature.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT02419742?tab=results

Safety and Efficacy of Trastuzumab as Part of Breast Cancer ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

10. herceptin.com herceptin.com/hcp/metastatic-breast-cancer/efficacy/clinical-results.html

Herceptin Clinical Trial Results Herceptin was studied in 2 pivotal trials involving more than 600 people with HER2+ metastatic breast cancer.