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

Trial Summary

What is the purpose of this trial?

The purpose of this preliminary research study is to see if patients discontinuing maintenance Herceptin and/or other anti-HER-2 treatments with monitoring in addition to radiologic imaging and routine blood work will stay in complete radiological remission and to determine how long patients are able to stay in complete radiological remission without 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 data supports the effectiveness of the drug trastuzumab for HER2-positive breast cancer?

Trastuzumab (Herceptin) has been shown to improve outcomes for patients with HER2-positive breast cancer, significantly reducing the risk of cancer recurrence and death. It is effective both in early-stage and advanced breast cancer, with studies showing prolonged remission in some patients even after stopping the drug. ^{1 2 3 4 5}

Is trastuzumab safe for humans?

Trastuzumab has been shown to be generally safe in humans, with the most significant side effect being cardiac dysfunction (heart problems) occurring in less than 5% of patients. It is not associated with common chemotherapy side effects like hair loss or low white blood cell counts. ^{1 6 7 8 9}

How does stopping HER-2 directed therapy for breast cancer differ from other treatments?

Stopping HER-2 directed therapy for breast cancer is unique because it explores the possibility of discontinuing treatment in patients who have achieved prolonged remission, which is not commonly done with standard HER-2 therapies that are typically continued until disease progression. This approach is being investigated to see if patients can maintain remission without ongoing treatment, potentially reducing side effects and treatment burden. ^{1 3 4 10 11}

Research Team

Elisa Krill Jackson, MD

Principal Investigator

University of Miami

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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]

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]

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 (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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

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

2. Hungary pubmed.ncbi.nlm.nih.gov

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

3. Switzerland pubmed.ncbi.nlm.nih.gov

Duration of trastuzumab in patients with HER2-positive metastatic breast cancer in prolonged remission. [2022]

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

Anti-HER2 Drugs for the Treatment of Advanced HER2 Positive Breast Cancer. [2023]

5. Japan pubmed.ncbi.nlm.nih.gov

Perspective of trastuzumab treatment. [2019]

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

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

7. Netherlands pubmed.ncbi.nlm.nih.gov

Long-term outcome of HER2 positive metastatic breast cancer patients treated with first-line trastuzumab. [2015]

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

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

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

Trastuzumab treatment after progression in HER2-positive metastatic breast cancer following relapse of trastuzumab-based regimens: a meta-analysis. [2020]

10. Greece 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. [2020]

11. France 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. [2022]