Sacituzumab Govitecan for Brain Metastases from Breast Cancer
Recruiting in Palo Alto (17 mi)
+142 other locations
Overseen byAndrew J Brenner
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: SWOG Cancer Research Network
Must not be taking: Antiretrovirals, Antiepileptics, Warfarin, others
Disqualifiers: Seizures, HIV, Hepatitis, others
No Placebo Group
Prior Safety Data
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?This phase II trial studies the effect of sacituzumab govitecan in treating patients with HER2-negative breast cancer that has spread to the brain (brain metastases). Sacituzumab govitecan is a monoclonal antibody, called sacituzumab, linked to a chemotherapy drug, called govitecan. Sacituzumab is a form of targeted therapy because it attaches to specific molecules on the surface of cancer cells, known as Trop-2 receptors, and delivers govitecan to kill them. Giving sacituzumab govitecan may shrink the cancer in the brain and/or extend the time until the cancer gets worse.
Will I have to stop taking my current medications?
The trial requires that you stop taking certain medications before joining. You must not have taken specific cancer treatments, enzyme-inducing anti-epileptic drugs, or warfarin shortly before starting the trial. If you're on HIV medications that interact with the trial drug, you may need to switch to different ones.
What data supports the effectiveness of the drug Sacituzumab Govitecan for brain metastases from breast cancer?
While there is no direct data on Sacituzumab Govitecan for brain metastases from breast cancer, other treatments like lapatinib and capecitabine have shown effectiveness in similar cases, suggesting that targeted therapies can be beneficial. Additionally, systemic treatments have shown significant antitumor activity in the central nervous system, indicating potential for drugs like Sacituzumab Govitecan.
12345What makes the drug Sacituzumab Govitecan unique for treating brain metastases from breast cancer?
Sacituzumab Govitecan is unique because it is an antibody-drug conjugate, which means it combines an antibody that targets cancer cells with a chemotherapy drug, potentially allowing for more direct delivery of the treatment to cancer cells. This approach may offer a novel way to treat brain metastases from breast cancer, where traditional treatments often struggle to penetrate the blood-brain barrier effectively.
36789Eligibility Criteria
This trial is for adults with HER2-negative breast cancer that has spread to the brain. They must have measurable brain metastasis, experienced CNS progression after treatment, and be in good physical condition (Zubrod status 0 or 1). Patients should not have had more than two seizures recently, no recent certain treatments or infections like HIV/hepatitis, and cannot be pregnant.Inclusion Criteria
I have another cancer, but it won't affect this trial's treatment.
I am fully active or restricted in physically strenuous activity but can do light work.
My heart is functioning well.
+10 more
Exclusion Criteria
I have had 2 or fewer seizures in the last 28 days.
Participants must not be pregnant or nursing
I haven't taken any cancer-targeting drugs in the last 21 days.
+8 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive sacituzumab govitecan intravenously over 1-3 hours on days 1 and 8. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Up to 2 years
Visits every 21 days
Follow-up
Participants are monitored for safety and effectiveness after treatment completion, with follow-ups every 3 months for 1 year and then every 6 months for another year.
2 years
Every 3 months for 1 year, then every 6 months for 1 year
Participant Groups
The trial tests Sacituzumab Govitecan's effectiveness on patients with brain metastases from breast cancer. It's a targeted therapy combining an antibody with chemotherapy to attack cancer cells directly without harming normal cells.
1Treatment groups
Experimental Treatment
Group I: Treatment (sacituzumab govitecan)Experimental Treatment1 Intervention
Patients receive sacituzumab govitecan IV over 1-3 hours on days 1 and 8. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Sacituzumab Govitecan is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Trodelvy for:
- Metastatic triple-negative breast cancer
- Locally advanced or metastatic urothelial cancer (withdrawn)
- Metastatic HR+/HER2- breast cancer
🇪🇺 Approved in European Union as Trodelvy for:
- Metastatic triple-negative breast cancer
🇨🇦 Approved in Canada as Trodelvy for:
- Metastatic triple-negative breast cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Rocky Mountain Cancer Centers-MidtownDenver, CO
Saint Alphonsus Medical Center-NampaNampa, ID
McKee Medical CenterLoveland, CO
McFarland Clinic PC - AmesAmes, IA
More Trial Locations
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Who Is Running the Clinical Trial?
SWOG Cancer Research NetworkLead Sponsor
Southwest Oncology GroupLead Sponsor
Gilead SciencesIndustry Sponsor
National Cancer Institute (NCI)Collaborator
References
All-oral combination of lapatinib and capecitabine in patients with brain metastases from HER2-positive breast cancer--a phase II study. [2022]Approximately one-third of patients with advanced, HER2+ve breast cancer (BC) develop brain metastases (BMs). The aim of this study is to investigate efficacy and tolerability of the combination of lapatinib and capecitabine (LC) in HER2+ve BC patients with brain metastases (BCBM).
CNS complications of breast cancer: current and emerging treatment options. [2021]In general, the development of CNS metastases of breast cancer depends on several prognostic factors, including younger age and a negative hormone receptor status. Also, the presence of a breast cancer 1, early onset (BRCA1) germline mutation and expression of the human epidermal growth factor receptor 2 (Her2/neu) proto-oncogene seem to contribute to an increased rate of development of CNS metastases. The choice of appropriate therapy for brain metastases also depends on prognostic factors, including the age of the patient, the Karnofsky performance score, the number of brain metastases and the presence of systemic disease. Surgery followed by whole brain radiation therapy (WBRT) is generally restricted to ambulant patients with a single brain metastasis without active extracranial disease. In patients who have two to four metastases, stereotactic focal radiotherapy (i.e. radiosurgery) with or without WBRT is usually indicated. In the remainder of patients, WBRT alone provides adequate palliation. Although breast carcinoma is sensitive to chemotherapy, the role of chemotherapy in the treatment of brain metastases is still unclear. Objective responses after cyclophosphamide-based therapies were reported in studies performed in the 1980s. Subgroup analysis of data from a randomised study indicates that survival may improve if WBRT is combined with the radiosensitiser efaproxiral. Interestingly, the Her2/neu antibody trastuzumab, which does not cross the blood-brain barrier, produces systemic responses and enhanced survival, without a clear effect on brain metastases. Breast cancer constitutes the most common solid primary tumour leading to leptomeningeal disease. Clinical symptoms such as cranial nerve dysfunction or a cauda equina syndrome can be treated with local radiotherapy. A randomised study in patients with leptomeningeal disease secondary to breast cancer has revealed that intrathecal chemotherapy is associated with substantially more adverse effects than non-intrathecal treatment, without a clear benefit in terms of response or survival. Intramedullary metastasis is rare but often presents with a rapidly progressive myelopathy. Local radiotherapy may preserve neurological function. Epidural spinal cord metastasis occurs in approximately 4% of patients and can lead to paraplegia. A randomised study has shown that surgical intervention together with local radiotherapy is superior to local radiotherapy alone.
Incidence, pattern and timing of brain metastases among patients with advanced breast cancer treated with trastuzumab. [2015]We aim to investigate the incidence, patterns and timing of brain metastases in advanced breast cancer patients who have previously received trastuzumab. Eighty-seven patients who had received trastuzumab for advanced breast cancer from November 1999 to September 2003 at the Royal Marsden Hospital were assessed. With a median follow-up period of 11 months from commencing trastuzumab, 23 patients developed brain metastases (30% at 1 year; 95% CI 58-82%). Among 57 patients who had clinical benefits on trastuzumab, 12 (21%) patients developed first disease progression in brain with 75% of them had isolated CNS progression. Moreover, among patients who received trastuzumab as first line treatment, isolated brain metastases were the initial site of progression in 17% patients. Nearly all patients developed parenchymal brain disease. This study shows brain metastases are common phenomenon in HER2 positive advanced breast cancer patients receiving trastuzumab and also may implicate the brain as a sanctuary site for early relapse in this patient cohort.
Impact of anti-HER2 therapy on overall survival in HER2-overexpressing breast cancer patients with brain metastases. [2021]Trastuzumab-based therapy after diagnosis of brain metastases (BM) may improve survival due to prolonged systemic disease control. We investigated whether lapatinib may yield additional survival benefit.
[Systemic treatment of brain metastases from breast cancer: cytotoxic chemotherapy and targeted therapies]. [2018]Prevalence of brain metastases is increasing in breast cancer. Brain metastases represent a poor-prognosis disease for which local treatments continue to play a major role. In spite of the presence of a physiological blood-brain barrier limiting their activity, some systemic treatments may display a significant antitumor activity at the central nervous system level. In HER2-positive metastatic breast cancer with brain metastases not previously treated with whole brain radiotherapy, capecitabine and lapatinib combination obtains a volumetric reponse in two thirds of patients (LANDSCAPE study). If confirmed, these results could modify in selected patients the layout of therapeutic strategies. Promoting novel targeted approaches and innovative therapeutic combinations is a critical need to improve survival of breast cancer patients with brain metastases.
HER2-positive breast cancer brain metastases: multiple responses to systemic chemotherapy and trastuzumab--a case report. [2018]Brain metastases from metastatic breast cancer typically occur in 10-15% of patients and are associated with survival of 3-6 months. Recent series have shown that women with HER2-positive metastatic breast cancer receiving the drug trastuzumab develop brain metastases more frequently than this, but also that continuation of trastuzumab after diagnosis of brain metastases in such patients is associated with extended survival. Authors have speculated that this is due to improved systemic control of disease; however, a possibility is that trastuzumab may have a beneficial effect on cerebral metastases themselves. We report the case of a woman with HER2-positive metastatic breast cancer who developed multiple brain metastases while on trastuzumab, in whom the addition of systemic chemotherapy to continued trastuzumab has produced multiple treatment responses associated with prolonged survival. This is the first report of its kind.
[Current possibilities of targeted therapy in the treatment of breast cancer with overexpression of HER-2/neu and metastatic lesions in the brain]. [2018]Targeted therapy (lapatinib and/or trastuzumab) in combination with chemotherapy (capecitabine) is highly effective in metastatic lesions of the brain in breast cancer patients with overexpress HER-2/neu. An objective response in the brain was achieved in 19 patients (55.9%). Complete regression was observed in 5 cases (14.7%), partial regression--14 (41.2%). Stabilization of tumor process in the brain was revealed in 12 patients (35.3%). There was marked improvement in the quality of life of the majority of patients due to the regression of symptoms and good tolerability of treatment.
Effective Treatment of Solitary Pituitary Metastasis with Panhypopituitarism in HER2-Positive Breast Cancer by Lapatinib. [2018]Brain metastasis affects one third of patients with HER2-positive breast cancer after treatment with trastuzumab. Surgical resection and radiation therapy are often unsuccessful at accomplishing complete control of metastasis. Lapatinib is presumed to cross the blood-brain barrier, and exhibits clinical activities for treatment of HER2-positive breast cancer. A 43-year-old woman was treated for early breast carcinoma with total mastectomy, axillary lymph-node dissection, and adjuvant chemotherapy with cyclophosphamide plus doxorubicin. After the end of adjuvant trastuzumab therapy, she was diagnosed with panhypopituitarism due to pituitary metastasis. Surgical removal and whole brain radiation therapy were performed, but a portion of viable tumor remained. Only taking lapatinib, the size of the metastatic lesion began to shrink. Trastuzumab may have controlled the micro-metastasis of breast cancer, but it was unable to control its progression to the central nervous system. Lapatinib is a possible option for HER2-positive metastatic breast cancer patients with brain metastasis.
Preclinical and Clinical Efficacy of Trastuzumab Deruxtecan in Breast Cancer Brain Metastases. [2023]Brain metastases can occur in up to 50% of patients with metastatic HER2-positive breast cancer. Because patients with active brain metastases were excluded from previous pivotal clinical trials, the central nervous system (CNS) activity of the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) is not well characterized.