Shorter HER2-targeted Therapy for Breast Cancer

Overseen By Danielle Allard, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Ottawa Hospital Research Institute

Must be taking: HER2 targeted therapy

Disqualifiers: Metastatic disease, Residual invasive disease, 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: 3

Duration: 6 months

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests if a shorter treatment period is effective for early-stage, HER2-positive breast cancer patients who have responded well to initial treatment. The aim is to reduce side effects and costs while maintaining treatment effectiveness. For many years, a longer treatment period has been the standard for these patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is trastuzumab safe for humans?

Trastuzumab, also known as Herceptin, is generally safe for humans, but it can cause some side effects. The most common serious side effect is heart-related issues, especially in patients who have had certain other cancer treatments. Other side effects can include mild reactions when the drug is first given, but these are usually not severe. ^{1 2 3 4 5}

How does the drug trastuzumab differ from other treatments for HER2-positive breast cancer?

Trastuzumab is unique because it specifically targets the HER2 protein on cancer cells, which is overexpressed in some aggressive breast cancers. This targeted approach can improve the effectiveness of chemotherapy and has been shown to significantly reduce relapse rates in HER2-positive breast cancer patients. ^{6 7 8 9 10}

What data supports the effectiveness of the drug Trastuzumab for breast cancer?

Research shows that Trastuzumab, when used alone or with chemotherapy, helps shrink tumors and improve survival in patients with HER2-positive breast cancer. It has been effective in both early and advanced stages of the disease, making it a successful targeted therapy for this type of cancer. ^{6 7 11 12 13}

Who Is on the Research Team?

Sharon McGee

Principal Investigator

Ottawa Hospital Research Institute

Are You a Good Fit for This Trial?

This trial is for people with early-stage HER2-positive breast cancer who've had a complete response to initial chemo and HER2 therapy. They should not have any remaining invasive cancer after pre-surgery treatment, be able to consent in English or French, and haven't yet received 6 months of HER2 therapy.

Inclusion Criteria

I had successful breast cancer treatment with no cancer found after surgery and took HER2 therapy for less than 6 months.

My breast cancer is in stages I-III and may be ER/PR positive or negative, but is HER2 positive.

I can give verbal consent and fill out forms in English or French.

Exclusion Criteria

My cancer is still present after initial treatment or has spread.

Anything in your life that might make it hard for you to follow the trial rules.

I cannot receive more HER2-targeted therapy after my initial treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 6 months of HER2-targeted therapy after achieving a pathological complete response to neoadjuvant systemic therapy

6 months

Every 3 weeks

Follow-up

Participants are monitored for disease-free survival, overall survival, and cardiac events

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Trastuzumab

Trial Overview The study tests if 6 months of HER2-targeted therapy (Trastuzumab) is effective for patients who responded well to initial treatments. It's a single-arm, multicentre trial focused on those with non-metastatic breast cancer seeking less intensive post-surgery treatment.

How Is the Trial Designed?

Group I: De-escalated HER2 targeted treatment Experimental Treatment 1 Intervention

Patients with early-stage HER2-positive breast cancer who demonstrate a pathological complete response at time of surgery.

Who Is Running the Clinical Trial?

Ottawa Hospital Research Institute

Lead Sponsor

Trials

585

Recruited

3,283,000+

Published Research Related to This Trial

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 a humanized monoclonal antibody that effectively targets the HER2/neu receptor, showing significant antitumor activity in patients with HER2/neu-amplified metastatic breast cancer based on multiple clinical trials.

When used in combination with chemotherapy, trastuzumab enhances treatment outcomes, improving time to progression, response rates, and overall survival, marking it as a pioneering example of targeted therapy in breast cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of treatment results with trastuzumab (Herceptin) in metastatic breast cancer. Hortobagyi, GN.[2016]

Trastuzumab significantly improves survival rates in breast cancer patients with HER2 overexpression, but it is associated with an increased risk of cardiac toxicity, particularly in patients who have previously received anthracyclines.

The mechanism of trastuzumab-related cardiac toxicity is not fully understood, but it may sensitize heart cells to stress and injury, leading to myocardial dysfunction without causing visible structural damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab cardiotoxicity: biological hypotheses and clinical open issues. Bria, E., Cuppone, F., Milella, M., et al.[2019]

The Short-HER study is a large phase III trial involving 2500 patients with HER2-positive breast cancer, designed to compare the effectiveness of long-term (18 doses) versus short-term (9 doses) trastuzumab treatment after chemotherapy.

The primary goal of the study is to determine which treatment duration leads to better disease-free survival, helping to optimize adjuvant therapy for patients with HER2-overexpressing tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicentric, randomized phase III trial of two different adjuvant chemotherapy regimens plus three versus twelve months of trastuzumab in patients with HER2- positive breast cancer (Short-HER Trial; NCT00629278). Guarneri, V., Frassoldati, A., Bruzzi, P., et al.[2018]

Adjuvant chemotherapy with trastuzumab for HER2 positive breast cancer significantly improves patient outcomes, providing an additional 0.84 quality-adjusted life years (QALY) and 1.16 life years gained (LYG) compared to chemotherapy without trastuzumab.

The cost-effectiveness analysis indicates that trastuzumab therapy has an incremental cost-effectiveness ratio (ICER) of approximately US$19,599.26 per QALY and US$14,180.68 per LYG, suggesting it may be considered cost-effective in Brazil under specific economic thresholds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of trastuzumab for early breast cancer in Brazil. Botelho, CH., Estevez-Diz, MDP., Campolina, AG.[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 (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]

Trastuzumab (Herceptin) is an effective treatment for metastatic breast cancer, especially when combined with paclitaxel, showing significant efficacy in a phase III study.

While trastuzumab is generally safe, it can cause infusion reactions and cardiotoxicity, particularly in patients with a history of high cumulative doses of anthracyclines, necessitating careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Trastuzumab (Herceptin)]. Tokuda, Y., Suzuki, Y., Saitou, Y., et al.[2015]

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]

Trastuzumab, while effective for treating HER2-positive breast cancer, can cause severe adverse effects such as significant edema, as demonstrated in a case of a 46-year-old woman who experienced extensive swelling after a single dose.

Treatment with methylprednisone was initiated to manage the edema, showing some mild reduction in symptoms, suggesting that early intervention may help mitigate this specific adverse reaction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab treatment of invasive breast ductal carcinoma induces severe edema: a case report. Zhao, H., Zheng, J., Wang, Q., et al.[2022]

The addition of trastuzumab (Herceptin®) to chemotherapy significantly improves overall survival in patients with HER2-positive early breast cancer, as shown by a systematic review of 31 studies published between 2008 and 2016.

The survival benefit of trastuzumab combined with chemotherapy has become more precise over time, reinforcing its status as the standard of care for HER2-positive early breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Herceptin® (trastuzumab) in HER2-positive early breast cancer: a systematic review and cumulative network meta-analysis. Wilson, FR., Coombes, ME., Brezden-Masley, C., et al.[2019]

Trastuzumab (Herceptin) is effective in reducing relapse rates in patients with HER2+ breast cancer, which represents 20% to 25% of cases, but many patients either do not respond or develop resistance to the treatment.

The review highlights the basal molecular subtype as a potential predictor of increased risk and a contributing factor to drug resistance in HER2+ breast cancer, suggesting the need for alternative therapies to overcome this challenge.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of anti-human epidermal growth factor receptor 2 therapies: predicting and overcoming herceptin resistance. Chung, A., Cui, X., Audeh, W., et al.[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]

Citations

1. England pubmed.ncbi.nlm.nih.gov

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

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

Overview of treatment results with trastuzumab (Herceptin) in metastatic breast cancer. [2016]

3. England pubmed.ncbi.nlm.nih.gov

Trastuzumab cardiotoxicity: biological hypotheses and clinical open issues. [2019]

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

Multicentric, randomized phase III trial of two different adjuvant chemotherapy regimens plus three versus twelve months of trastuzumab in patients with HER2- positive breast cancer (Short-HER Trial; NCT00629278). [2018]

5. England pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of trastuzumab for early breast cancer in Brazil. [2022]

6. England pubmed.ncbi.nlm.nih.gov

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

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

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

8. Japan pubmed.ncbi.nlm.nih.gov

[Trastuzumab (Herceptin)]. [2015]

9. Slovakia pubmed.ncbi.nlm.nih.gov

Trastuzumab in the adjuvant treatment of breast cancer. [2016]

10. China pubmed.ncbi.nlm.nih.gov

Trastuzumab treatment of invasive breast ductal carcinoma induces severe edema: a case report. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Herceptin® (trastuzumab) in HER2-positive early breast cancer: a systematic review and cumulative network meta-analysis. [2019]

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

Current status of anti-human epidermal growth factor receptor 2 therapies: predicting and overcoming herceptin resistance. [2021]

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

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