Shorter HER2-targeted Therapy for Breast Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Ottawa Hospital Research Institute
Must be taking: HER2 targeted therapy
Disqualifiers: Metastatic disease, Residual invasive disease, others
No Placebo Group
Prior Safety Data
Approved in 4 jurisdictions
Trial Summary
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.
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.
12345Is 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.
678910How 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.
24111213Eligibility Criteria
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.
Trial Timeline
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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: De-escalated HER2 targeted treatmentExperimental Treatment1 Intervention
Patients with early-stage HER2-positive breast cancer who demonstrate a pathological complete response at time of surgery.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
The Ottawa Hospital Cancer CentreOttawa, Canada
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Who Is Running the Clinical Trial?
Ottawa Hospital Research InstituteLead Sponsor
References
Trastuzumab, an appropriate first-line single-agent therapy for HER2-overexpressing metastatic breast cancer. [2021]Overexpression of the HER2/Neu (ErbB2) proto-oncogene is associated with breast cancer progression and poor patient prognosis. Herceptin (trastuzumab) is a humanized IgG1 against the ectodomain of the HER2 receptor. In combination with chemotherapy, it induces regression of HER2-overexpressing metastatic breast tumors and prolongs patient survival. Single-agent Herceptin in patients with HER2-amplified breast tumors also induces a definite objective response and clinical benefit rates, and is well tolerated. These data suggest that Herceptin is an effective first-line single-agent therapy for a predictable cohort of metastatic breast cancers and can therefore be used as a platform for therapeutic discovery against tumors that overexpress HER2.
Overview of treatment results with trastuzumab (Herceptin) in metastatic breast cancer. [2016]HER2/neu amplification/overexpression confers more aggressive and malignant characteristics on breast cancer cells. Patients with HER2/neu-amplified breast cancer have a worse prognosis than those with normal HER2/neu expression. Over the past decade, the intracellular signaling pathways associated with this growth factor receptor have been elucidated. Multiple therapeutic strategies that target the HER2/neu oncoprotein are under development. Trastuzumab (Herceptin; Genentech, Inc, South San Francisco, CA), a humanized monoclonal antibody that binds to the extracellular domain of the HER2/neu receptor, has undergone phase I, II, and III clinical trials. These studies have shown that, as a single agent, trastuzumab has substantial and reproducible antitumor activity in HER2/neu-amplified metastatic breast cancer. In addition, when added to chemotherapy, trastuzumab improves antitumor efficacy as measured by time to progression, response rate, and survival. Additional chemotherapy/trastuzumab combinations are under active evaluation, and new schedules of administration are being tested. Thus, trastuzumab is the first successful example of molecularly targeted therapy in the management of metastatic breast cancer.
Trastuzumab cardiotoxicity: biological hypotheses and clinical open issues. [2019]Trastuzumab has significantly improved the prognosis of breast cancer patients overexpressing the human epidermal growth factor receptor 2 (HER2). This result has been achieved in all disease settings, by increasing overall survival in early stage and advanced disease and by increasing pathological complete responses in neoadjuvant disease.
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]Trastuzumab, a monoclonal antibody against the HER2 receptor, is currently approved as a part of adjuvant therapy for patients with HER2-overexpressing breast tumors. The Short-HER study is a phase III randomized, multicentric Italian trial aimed at testing the optimal duration of adjuvant trastuzumab. In this trial, 2500 patients with HER2-positive breast cancer will be randomized to receive the following: (arm A, long) 4 courses of anthracycline- based chemotherapy (doxorubicin/cyclophosphamide or epidoxorubicin/cyclophosphamide) followed by 4 courses of docetaxel or paclitaxel in combination with trastuzumab, followed by 14 additional courses of trastuzumab administered every 3 weeks (for a total of 18 3-weekly doses of trastuzumab); or (arm B, short) 3 courses of 3-weekly docetaxel in combination with weekly trastuzumab (for a total of 9 weekly doses of trastuzumab) followed by 3 courses of 5-fluorouracil/epirubicin/cyclophosphamide. The primary objective is disease-free survival.
Cost-effectiveness analysis of trastuzumab for early breast cancer in Brazil. [2022]Adjuvant chemotherapy with trastuzumab for HER2 positive breast cancers has brought considerable benefits to disease-free survival and overall survival.
Tolerability in patients receiving trastuzumab with or without chemotherapy. [2020]One of the major expectations from the use of humanized monoclonal antibodies in cancer therapy has been that of exploiting the specificity and sensitivity of the immune system to achieve selective therapeutic effects devoid of the often severe toxicity caused by chemotherapy. The tolerability of trastuzumab (Herceptin) as it emerged from the trials where the drug was used as a single agent or in combination with chemotherapy largely confirmed that expectation. Adverse events most frequently encountered include mild-to-moderate, transient effects related to administration of the first dose of trastuzumab. The incidence of severe or serious adverse effects attributable to trastuzumab was low. However, the occurrence of cardiac toxicity that was unexpectedly high, especially in patients previously or concomitantly treated with anthracyclines, could not be predicted on the basis of the putative mechanism of action of the antibody. The safety profile of trastuzumab is discussed here with a particular focus on cardiotoxicity and the issues relating to patient management during trastuzumab therapy.
Clinical trials of single-agent trastuzumab (Herceptin). [2015]The HER2 gene (also known as neu and as c-erb-B2) encodes a 185-kd transmembrane glycoprotein receptor with intrinsic tyrosine kinase activity. HER2 is overexpressed in 25% to 30% of human breast cancers, plays a role in the pathogenesis of breast cancer, and predicts for a worse prognosis in patients with metastatic disease. Trastuzumab (Herceptin; Genentech, Inc, So. San Francisco, CA), a humanized monoclonal antibody that targets the HER2 oncogene receptor, was shown to be active in preclinical models. In initial phase I clinical trials, trastuzumab was found to be safe and to exhibit dose-dependent pharmacokinetics. Three phase II studies of single-agent trastuzumab, which was administered weekly in the outpatient setting, have now been conducted in patients with HER2-overexpressing metastatic breast cancer. In the initial phase II study, the response rate was 11% in a heavily pretreated patient population. In a pivotal follow-up study of single-agent trastuzumab, more than 200 patients who had received at least one prior chemotherapeutic regimen for metastatic disease were entered. Despite a number of unfavorable baseline characteristics, the response rate reported by an independent response evaluation committee was 15%. A more recent study in previously untreated patients has shown a 23% response rate. The median duration of response in these trials has ranged from 6.6 to 9.1 months. In these three phase II studies, trastuzumab has been shown to be safe. The most clinically significant adverse event has been cardiac dysfunction syndrome, which occurred in less than 5% of patients. Trastuzumab is not associated with the other commonly observed side effects of chemotherapy, such as alopecia, mucositis, and neutropenia. The results from these studies demonstrate that trastuzumab is active and safe in patients with metastatic HER2-overexpressing breast cancer.
[Trastuzumab (Herceptin)]. [2015]The HER 2/neu protein is thought to be a unique and useful molecular target for antibody therapy of cancers overexpressing the HER 2/neu gene. The recombinant humanized anti-HER 2 monoclonal antibody trastuzumab (Herceptin) has been available for clinical use in metastatic breast cancer in Japan since June 2001. Some breast cancer patients have responded to trastuzumab alone. A phase III study showed significant efficacy of combination use with paclitaxel compared with paclitaxel alone. Trastuzumab has some toxicities including infusion reaction and cardiotoxicity. It is very rare that infusion reaction manifests lethally. Although trastuzumab should not be concurrently used with an anthracycline, cardiotoxicity was also identified in patients treated with trastuzumab alone. The cumulative dose of anthracycline has not yet been identified as a risk factor, but patients who have received a high cumulative dose should be treated with special caution. In this article, the details of this novel biologic agent are reviewed from basic and clinical studies.
Trastuzumab in the adjuvant treatment of breast cancer. [2016]Four large randomized trials to assess efficacy and toxicity of trastuzumab in adjuvant systemic therapy of breast cancer have been initiated. Results clearly demonstrate, that adjuvant treatment of trastuzumab significantly improves outcomes for women with HER2 positive breast cancer. The clinically most significant adverse events of trastuzumab are serious-infusion related reactions and cardiotoxicity. Benefit for patient should be considered according to advantage versus risk (Tab. 1, Fig. 2, Ref. 17) Full Text (Free, PDF) www.bmj.sk.
Trastuzumab treatment of invasive breast ductal carcinoma induces severe edema: a case report. [2022]Trastuzumab, a monoclonal antibody which binds to the extracellular domain of human epidermal growth factor receptor 2 (HER2), is the first biological drug approved for the treatment of HER2-positive breast cancer. However, trastuzumab exhibits a series of clinical adverse effects, including cardiac toxicity, nerve damage, abnormal liver function, thrombocytopenia, etc.
Herceptin® (trastuzumab) in HER2-positive early breast cancer: a systematic review and cumulative network meta-analysis. [2019]Originator trastuzumab (Herceptin®; H) is an antibody-targeted therapy to treat patients with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (EBC). We investigated the overall survival (OS) advantage conferred by the addition of H to chemotherapy for HER2+ EBC patients and how the OS advantage changed over time.
Current status of anti-human epidermal growth factor receptor 2 therapies: predicting and overcoming herceptin resistance. [2021]Human epidermal growth factor receptor 2-overexpressing (HER2+) breast cancer occurs in 20% to 25% of cases and is associated with poor prognosis. Trastuzumab (Herceptin; Genentech, South San Francisco, CA) is a monoclonal antibody targeting the HER2 extracellular domain that has been shown to significantly reduce relapse rates. However, some patients with HER2+ tumors do not respond to Herceptin, and 60% to 85% of patients with HER2+ metastatic breast cancer acquire resistance within a short time period. In this review, we discuss proposed mechanisms of action of trastuzumab and trastuzumab resistance and various drugs that have been developed to overcome drug resistance. We introduce the basal molecular subtype as a predictor of increased risk in HER2+ breast cancer and a possible alternative cause of drug resistance.
Trastuzumab: targeted therapy for the management of HER-2/neu-overexpressing metastatic breast cancer. [2015]Breast cancers are a biologically heterogeneous group of mammary tumors with distinct natural histories and varied responses to established therapies. They have long been divided into those that are hormone sensitive [as defined by expression of the estrogen receptor alpha (ERalpha) and/or the progesterone receptor (PR)] and those that are not. Notably, only those breast cancers that express ERalpha and/or PR typically respond to hormonal therapy with tamoxifen, aromatase inhibitors, or the newer agent fulvestrant. More recently, the transmembrane tyrosine kinase receptor HER-2/neu was identified as an oncogene overexpressed by about 30% of breast cancers. These HER-2/neu-overexpressing breast cancers define a subset of breast tumors that are characteristically more aggressive, and women who develop them have a shorter survival. Trastuzumab (Herceptin), a humanized monoclonal antibody specific for HER-2/neu, has revolutionized the management of metastatic HER-2/neu-overexpressing breast cancers. As a single agent, it produces response rates similar to those of many single-agent chemotherapeutic agents active in metastatic breast cancer and has limited toxicity. Combining trastuzumab with chemotherapy can result in synergistic antitumor activity. The clear efficacy of trastuzumab against HER-2/neu-overexpressing metastatic breast cancer has led to a keen interest in testing its role in the management of early breast cancer, and multiple large clinical trials are currently in progress. This review summarizes the available clinical data on the use of trastuzumab in HER-neu-overexpressing breast cancer and briefly highlights emerging opportunities for innovative, trastuzumab-based breast cancer therapies.