Stopping HER-2 Directed Therapy for Breast Cancer
(Free-HER Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
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
Approved in 5 Jurisdictions
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.
12345Is 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.
16789How 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.
1341011Eligibility 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.
+7 more
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
+5 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: anti-HER-2 GroupExperimental Treatment1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of MiamiMiami, FL
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Who Is Running the Clinical Trial?
University of MiamiLead Sponsor
References
Dual HER2 Suppression with Lapatinib plus Trastuzumab for Metastatic Inflammatory Breast Cancer: A Case Report of Prolonged Stable Disease. [2022]Continuous therapy targeting human epidermal growth factor receptor 2 (HER2) is recommended until disease progression for patients with HER2-overexpressing (HER2+) metastatic breast cancer. Prolonged stable disease has been observed with such maintenance therapy using trastuzumab, but the frequency of these cases remains low. Whether combined maintenance therapy with two different HER2-targeted agents could improve the rates of durable progression-free survival compared with trastuzumab alone is under investigation.
[Trastuzumab (Herceptin) in the adjuvant treatment of HER-2-positive early breast cancer]. [2015]The prognosis of HER-2-positive breast cancer (characterized by amplification of the HER-2 oncogene and/or overexpression of HER-2 receptor) is unfavourable. Trastuzumab (Herceptin), a monoclonal antibody against HER-2 receptor can improve the outcome of HER-2-positive breast cancer. Up to now this was proven only in advanced disease. Recently five large multicentric phase III adjuvant trials gave level one evidence on the benefit of adjuvant treatment with Herceptin, concerning disease-free survival (DFS) and overall survival (OS). Herceptin has decreased the relative risk of recurrence with about 50% and that of death with nearly 30% in HER-2-positive early breast cancer. Based on these results Herceptin, together with chemotherapy, has been recently approved for the adjuvant treatment of HER-2-positive breast cancer.
Duration of trastuzumab in patients with HER2-positive metastatic breast cancer in prolonged remission. [2022]Outcomes in metastatic breast cancer (mbc) positive for her2 (human epidermal growth factor receptor 2) are generally unfavourable. Trastuzumab has revolutionized the prognosis of her2-positive mbc. Some her2-positive mbc patients go into prolonged remission, and a few patients remain in remission even after discontinuation of trastuzumab, suggesting the possibility of a cure. In our practice, 4 her2-positive mbc patients treated with chemotherapy and trastuzumab have remained in remission on maintenance therapy for 5 years or more. Of those 4 patients, 2 have continued in remission after discontinuation of trastuzumab for more than 1 year. The objective of the present paper was therefore to address the duration of trastuzumab therapy in her2-positive mbc patients in prolonged remission.
Anti-HER2 Drugs for the Treatment of Advanced HER2 Positive Breast Cancer. [2023]Approximately 15-20% of breast cancers (BC) demonstrate HER2 overexpression/gene amplification. Historically, before the era of HER2-directed therapies, this subtype was associated with poor prognosis. Anti-HER2 agents dramatically changed the natural course of disease and significantly prolonged patients' survival. In recent years, a number of new anti-HER2 therapies have been developed, and their approvals offer new therapeutic options for patients with advanced HER2-positive breast cancer. At present, HER2 pathway blocking drugs used in the treatment of metastatic breast cancer worldwide include trastuzumab and pertuzumab in the first-line treatment; trastuzumab deruxtecan and trastuzumab emtansine in the second line; and tucatinib, neratinib, lapatinib, and margetuximab in further lines of treatment of advanced HER2 positive breast cancer. Additionally, there are many clinical trials underway evaluating drugs blocking the HER2 pathway in advanced disease setting. This article presents new treatment options, discussing the most important findings from clinical trials and real-world reports, clinical benefits and risks of treatment, as well as efficacy of re-treatment with trastuzumab in metastatic breast cancer. New data challenge the current standards, and a number of questions arise regarding the optimal sequence of anti-HER2 targeted therapies, the optimal combination, including endocrine agents in luminal HER2 positive tumors and treatment of special patient population such as patients with brain metastases (BM).
Perspective of trastuzumab treatment. [2019]Trastuzumab (Herceptin) has many benefits for metastatic breast cancer patients with HER2 overexpression/amplification. Trastuzumab alone or trastuzumab in combination with chemotherapy regimens are standard treatment worldwide as first line therapy for metastatic breast cancer patients with HER2 overexpression/amplification. Furthermore, an international collaboration for adjuvant trastuzumab trials showed last year that trastuzumab treatment improves disease-free and overall survival after or in combination with adjuvant chemotherapy. However, there are many uncertain issues concerning trastuzumab adjuvant and metastatic treatment, such as treatment beyond disease progression (PD), combination with hormone therapy, duration of adjuvant treatment, and cardiac safety of long term treatment.
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.
Long-term outcome of HER2 positive metastatic breast cancer patients treated with first-line trastuzumab. [2015]Trastuzumab has changed the natural history of metastatic HER2 positive breast cancer. Some patients remain well and in remission for many years. There is currently no established duration after which trastuzumab in the advanced setting can be safely discontinued. This study aims to evaluate long-term efficacy and cardiac safety of trastuzumab when used as first-line treatment for patients with metastatic HER2 positive breast cancer.
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.
Trastuzumab treatment after progression in HER2-positive metastatic breast cancer following relapse of trastuzumab-based regimens: a meta-analysis. [2020]Background: This meta-analysis assessed the safety and effectiveness of retreatment with trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (HER2+MBC). Materials and methods: Randomized controlled trials (RCTs) and cohort studies that compared the clinical outcomes of continuation and termination of trastuzumab treatment in HER2+MBC after failure of trastuzumab-based regimens were analyzed. Pooled estimates of time to progression (TTP) survival, overall survival (OS), the incidence of adverse events and central nervous system (CNS) perturbations were determined. Results: Four RCTs and six cohort studies with 2,409 patients were identified. The continuation of trastuzumab presented a statistical significance in prolonging TTP (HR 0.88; 95% CI: 0.82-0.94; P<0.000) and OS (HR 0.87; 95% CI: 0.82-0.93; P<0.000). Furthermore, retreatment with trastuzumab did not add to the risk of cardiac events (relative risk, 2.48; 95% CI: 0.86-7.15) or the incidence of CNS metastasis (P=0.83). Conclusion: Our findings confirm the clinical benefits and safety of retreatment therapy with trastuzumab for HER2-positive patients with metastatic cancer of the breast that had progressed during trastuzumab-based treatment regimens.
Resumption of Trastuzumab in Patients With Disease Recurrence After (Neo-) Adjuvant Anti-HER2-therapy in Patients With HER2-positive Breast Cancer. [2020]HER2-positive breast cancers eventually relapse in about one third of patients. Is anti-HER2-directed therapy with Herceptin® (trastuzumab) effective in re-treatment? Between 2008 and 2018, 216 patients with recurrent HER2-positive breast cancer (BC) were re-treated with Herceptin (HER) during first-line therapy. This study assessed the effectiveness and tolerability of re-treatment with HER.
Prolonged complete remission of metastatic HER2-positive breast cancer after continuous trastuzumab treatment: a case report and review of the literature. [2022]Metastatic breast cancer is considered an incurable disease. Targeted treatments against the human epidermal growth factor receptor 2 (HER2), however, significantly improve survival in patients with metastatic HER2-positive breast cancer. Some patients may respond with prolonged complete remission. Evidence on safety of long-term trastuzumab and risk of relapse after trastuzumab cessation is limited. We present a case of an 81-year-old patient with HER2-amplified metastatic breast cancer (MBC) in the liver. Following taxane-based chemotherapy in combination with trastuzumab after local treatment resulted in a complete radiological remission after 21 months of trastuzumab maintenance therapy. The patient remains in complete remission 6 years later and continues to receive trastuzumab as maintenance therapy. Prolonged remission in cases with complete response under trastuzumab-based regimens for metastatic HER2-positive breast cancer can be observed in some patients. Reviewing the few available cases published in the literature, these patients share some common characteristics: hormone receptor negative disease and metastases to the liver. There is no evidence that trastuzumab maintenance treatment can be safely interrupted after a certain time period.