Stopping Anti-HER2 Therapy for Breast Cancer

Not currently recruiting at 15 trial locations

Overseen By Heather A Parsons, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must be taking: Anti-HER2 therapy

Must not be taking: Investigational agents

Disqualifiers: Psychiatric illness, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety of stopping anti-HER2 treatment for patients with HER2-positive metastatic breast cancer (MBC) after an exceptional response, defined as cancer control for at least three years. The study will compare two groups: one will stop treatment and undergo close monitoring, while the other will continue their current treatment. It seeks participants who have been on anti-HER2 therapy (such as Trastuzumab, also known as Herceptin) for at least three years without cancer progression and are willing to stop treatment for the trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires participants to stop anti-HER2 therapy if they are in the intervention arm. However, if you have ER-positive disease, you should continue your endocrine therapy.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that stopping trastuzumab, a common treatment for HER2-positive cancer, is usually well-tolerated. One study found that only 13.3% of patients experienced a recurrence of cancer within 11 to 66 months after stopping trastuzumab. This suggests that many patients do not face a quick return of cancer after discontinuing the drug.

The FDA has approved trastuzumab for other uses, which supports its safety profile. Although some risks exist, data indicates that many patients stop the treatment without serious issues. Patients should always consult their doctor to determine if this is the right choice. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores the potential of stopping anti-HER2 therapy for certain breast cancer patients. Unlike the standard approach where patients remain on Trastuzumab indefinitely, this trial investigates whether patients can safely discontinue the treatment after a period of stability. The trial's unique feature is its focus on long-term outcomes, aiming to determine if patients can maintain their health without ongoing therapy, which could reduce side effects and improve quality of life. By studying this new treatment protocol, researchers hope to find a balance between effective cancer control and minimizing treatment burdens.

What evidence suggests that stopping anti-HER2 treatment could be effective for HER2-positive metastatic breast cancer?

Research has shown that treatments like trastuzumab effectively manage HER2-positive metastatic breast cancer. In previous studies, only about 13.3% of patients who stopped trastuzumab after responding well experienced cancer recurrence over an average follow-up of 32 months. This trial will compare two approaches: one group will stop anti-HER2 therapy, while another will continue treatment. The focus is on identifying patients whose cancer has been controlled for three years or more. If cancer returns, restarting trastuzumab has proven effective and does not cause unexpected side effects. This evidence suggests that stopping the treatment might be safe for carefully selected patients. ^{1 2 3 4 6}

Who Is on the Research Team?

Nancy U Lin, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults over 18 with HER2-positive metastatic breast cancer who've had a great response to anti-HER2 therapy for at least 3 years. They must be able to follow the study plan and continue endocrine therapy if they have ER-positive disease. Those with certain stable brain conditions or other cancers that don't affect this study can join too.

Inclusion Criteria

I've been on a first-line anti-HER2 therapy for my metastatic disease for at least 3 years without my cancer getting worse.

My breast cancer is advanced, cannot be surgically removed, and is HER2 positive.

I had a single cancer growth treated without affecting my brain.

Exclusion Criteria

All English-speaking patients will participate in the PRO measures. Patients that do not read or understand English are eligible to participate but will be exempt from the patient completed questionnaires

You are currently taking any experimental drugs for breast cancer treatment.

Participants with psychiatric illness/social situations that would limit compliance with study requirements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment Cessation

Participants in cohort 2 stop anti-HER2 therapy and undergo clinical follow-up

1 year

Visits every 4-6 weeks, at 12 weeks, and every 12 weeks thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment cessation

10 years

Imaging surveillance every 3-6 months

What Are the Treatments Tested in This Trial?

Interventions

• Cessation of anti-HER2 treatment
• Trastuzumab

Trial Overview The STOP-HER2 trial is testing whether patients with an exceptional response to anti-HER2 treatment can safely stop the therapy without their cancer progressing. An 'exceptional response' means their cancer has been under control for three years or more on current treatment.

How Is the Trial Designed?

Group I: Cohort 2: - Stop Anti-HER2 Therapy Experimental Treatment 1 Intervention

Participants will have scans 30 days prior to starting study. Week 1 participants will stop anti-HER2 therapy then undergo clinical follow-up every 4-6 weeks, at 12 weeks, and every 12 weeks thereafter. Visits will include interval history, physical exam, concomitant medications and blood draw for tumor marker assessment and research blood. Participants will undergo restaging scans every 12 weeks (+/- 2 weeks). Participants remaining progression-free after one year off treatment, may continue off anti-HER2 therapy indefinitely, with imaging surveillance suggested to be every 3-6 months at the discretion of the treating oncologist and will be followed up to 10 years Participants with disease progression after stopping anti-HER2 therapy, treatment is at discretion of the treating physician but resuming the pre-study regimen is strongly encouraged.

Group II: Cohort 1: Observational Continue Anti-HER2 Therapy Active Control 1 Intervention

Participants will have scans 30 days prior to starting study then undergo clinical follow-up 4-6 weeks after study initiation, at 12 weeks, and every 12 weeks thereafter. Visits will include interval history, physical exam, concomitant medications and blood draw for tumor marker assessment and research blood. Participants will undergo restaging scans every 12 weeks (+/- 2 weeks).

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

Approved in European Union as Herceptin for:

• Early breast cancer
• Metastatic breast cancer
• Advanced gastric cancer

Approved in United States as Herceptin for:

• Adjuvant treatment of HER2-positive breast cancer
• Metastatic breast cancer
• Advanced gastric cancer

Approved in Canada as Herceptin for:

• Early breast cancer
• Metastatic breast cancer
• Advanced gastric cancer

Approved in Japan as Herceptin for:

• Breast cancer
• Gastric cancer

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Gateway for Cancer Research

Collaborator

Trials

47

Recruited

2,500+

Susan G. Komen Breast Cancer Foundation

Collaborator

Trials

68

Recruited

220,000+

Translational Breast Cancer Research Consortium

Collaborator

Trials

27

Recruited

3,100+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Omalizumab, a monoclonal antibody targeting IgE, has been shown to significantly reduce or eliminate symptoms of chronic urticaria in clinical trials conducted between 2011 and 2013.

The recommended dosage for treating chronic urticaria is 300 mg every 4 weeks, which is different from the dosing used for asthma, but it is important to note that omalizumab does not lead to lasting symptom remission, and the optimal treatment duration remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential role of omalizumab in the treatment of chronic urticaria. Stitt, JM., Dreskin, SC.[2015]

A case report highlighted that switching from omalizumab to mepolizumab resulted in a relapse of urticaria, indicating the importance of monitoring patients during medication changes.

The successful combination of biologics in this case suggests that using multiple treatments may be an effective strategy for managing persistent urticaria symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The six million dollar man. Volpato, M., Nowak, S., Bourrain, JL., et al.[2021]

In a study of 33 patients with relapsing-remitting multiple sclerosis who switched from natalizumab (NAT) to fingolimod (FTY), 61% experienced relapses after stopping NAT, with the highest relapse rates occurring 13-24 weeks post-switch.

The last Expanded Disability Status Scale (EDSS) score before switching was a strong predictor of future relapses during FTY therapy, with patients having an EDSS >3 showing a significantly higher risk of relapse compared to those with an EDSS ≤3.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors for multiple sclerosis relapses after switching from natalizumab to fingolimod. Hoepner, R., Havla, J., Eienbröker, C., et al.[2022]

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]

Trastuzumab significantly improves treatment outcomes for women with HER2 positive breast cancer, as shown in four large randomized trials.

The main safety concerns associated with trastuzumab are serious infusion-related reactions and cardiotoxicity, highlighting the need to weigh the benefits against these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab in the adjuvant treatment of breast cancer. Svetlovska, D., Mardiak, J., Kristova, V.[2016]

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]

Herceptin (trastuzumab) is an effective treatment for metastatic breast cancer that overexpresses the HER2/Neu proto-oncogene, showing significant tumor regression and improved patient survival when used with chemotherapy.

As a single-agent therapy, Herceptin also provides a clear clinical benefit and is well tolerated, making it a strong first-line option for patients with HER2-amplified breast tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab, an appropriate first-line single-agent therapy for HER2-overexpressing metastatic breast cancer. Arteaga, CL.[2021]

Trastuzumab (Herceptin) is highly effective in treating metastatic breast cancers that overexpress the HER-2/neu receptor, showing response rates comparable to traditional chemotherapy with significantly lower toxicity.

The success of trastuzumab in advanced cases has prompted ongoing clinical trials to explore its potential benefits in early-stage HER-2/neu-overexpressing breast cancer, indicating a shift towards more targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab: targeted therapy for the management of HER-2/neu-overexpressing metastatic breast cancer. Emens, LA.[2015]

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]

Discontinuing natalizumab (NTZ) in patients with relapsing-remitting multiple sclerosis (RRMS) can lead to a significant risk of disease reactivation, with clinical relapses occurring in 9-80% of patients, peaking at 4-7 months after stopping treatment.

Younger patients, those with a higher number of previous relapses, and those with more gadolinium-enhanced lesions before starting NTZ are at greater risk for experiencing post-NTZ disease reactivation, according to a meta-analysis of 1183 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-natalizumab disease reactivation in multiple sclerosis: systematic review and meta-analysis. Prosperini, L., Kinkel, RP., Miravalle, AA., et al.[2022]

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]

Biological therapy for rheumatoid arthritis can potentially be stopped in many patients after achieving low disease activity or remission for at least 6 months, but success rates vary widely from 0-97% across different studies.

Retreatment with biological therapy is effective in 70-100% of patients who experience a disease flare after discontinuation, with only mild infusion reactions reported, indicating that monitoring and retreatment are generally safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do we need guidelines to stop as well as to start biological therapies for rheumatoid arthritis? van den Broek, M., Lems, WF., Allaart, CF.[2017]

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]

In a study of 39 elderly patients with HER-2-positive breast cancer, 82.1% completed one year of trastuzumab treatment, indicating good tolerance to the therapy.

While 28.2% experienced adverse events, including congestive heart failure and lower left ventricular ejection fraction, most patients managed to recover with appropriate treatment, highlighting the need for careful monitoring in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of adjuvant trastuzumab for HER-2-overexpressing elderly breast cancer patients: a multicenter cohort study. Sawaki, M., Mukai, H., Tokudome, N., et al.[2015]

Trastuzumab (Herceptin) has demonstrated significant antitumor activity in patients with HER-2-positive metastatic breast cancer, improving response and survival rates when combined with first-line chemotherapy.

Recent clinical trials have focused on new chemotherapy approaches for node-positive breast cancer, laying the groundwork for ongoing studies that incorporate trastuzumab into treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ongoing and planned adjuvant trials with trastuzumab. Perez, EA., Hortobagyi, GN.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7735777/

Impact of Stopping Trastuzumab in Early Breast Cancer Adjuvant trastuzumab for early-stage (I-III) HER2-positive breast cancer (BC) has led to statistically significant improvement in cancer outcomes but ...

2. dana-farber.org dana-farber.org/clinical-trials/22-655

The STOP-HER2 Trial: A Phase 2 Study of ... This study is being done to see if anti-HER2 treatment be safely stopped in patients with. HER2-positive metastatic breast cancer (MBC) that have had ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10232540/

Termination of trastuzumab in HER2-positive metastatic ... After termination of trastuzumab, at a median follow-up of 32 months (11–66), recurrence was detected in two (13.3%) patients. We detected that ...

4. cardiooncologyjournal.biomedcentral.com cardiooncologyjournal.biomedcentral.com/articles/10.1186/s40959-020-00081-9

Clinical impact of interruption in adjuvant Trastuzumab ... A total of 369 patients received trastuzumab therapy; 106 (29%) patients experienced treatment interruption at least once and 42 (11%) ...

5. ar.iiarjournals.org ar.iiarjournals.org/content/40/7/3973

Resumption of Trastuzumab in Patients With Disease ... Re-therapy with HER in the first-line setting of advanced HER2-positive breast cancer is effective and without unexpected or intensified adverse events.

6. herceptin.com herceptin.com/hcp/adjuvant-breast-cancer/efficacy/clinical-results.html

Herceptin Clinical Trial Results Review information on clinical studies for Herceptin® (trastuzumab) in HER2+ Adjuvant Breast Cancer. See Full Safety and Boxed Warnings for more ...