FSRT in Breast Cancer Patients With Brain Metastases

Study Overview
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Brief Summary
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Brain metastasis accounted for 10-15% of all breast cancer patients and even higher in patients with triple negative and HER2 overexpressed subtype. Stereotactic radiation is the standard option for patients with 1-4 brain metastases. Among patients with 1-4 brain metastases, many studies suggest that stereotactic radiation results in fewer neurologic side effects than whole brain radiation. Also, several studies had demonstrated that 5-10 lesions had similar overall survival by using whole brain radiotherapy or stereotactic radiotherapy. Fractionated stereotactic radiotherapy(FSRT) is increasingly administered in the brain metastatic patients and retrospective studies had shown that FSRT had better local control and lower brain radiation necrosis than single fraction stereotactic radiation. Therefore, In this study, we explore to treat 1-10 brain metastasis lesion in breast cancer patients with FSRT.

Detailed Description
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Breast cancer patients with 1-10 brain metastasis will be treated with FSRT for brain metastasis. 3 to 5 fractions and 8Gy per fraction will be used for these patients based on the lesion number and volume.

Official Title
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A Phase II Pilot Study of Fractionated Stereotactic Radiotherapy(FSRT) in Breast Cancer Patients With 1 to 10 Brain Metastases

Conditions
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Breast Cancer, Brain Metastases

Intervention / Treatment
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* Radiation: Fractionated stereotactic radiotherapy(FSRT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed HER2 positive advanced breast cancer Age>18 years. 1 to 10 brain metastases confirmed by enhanced brain MRI KPS≥70 Life expectancy of more than 12 weeks Prior therapy of oral dexamethasone not exceeding 16mg/d Time interval from prior therapy was more than 2 weeks, and evaluation of adverse events is no more than grade 1. Maximum diameter of intracranial metastases is less than 3cm measured by enhanced brain MRI(2-3mm) Prior endocrine therapy were allowed Anti-Her2 targeted treatment were allowed Screening laboratory values must meet the following criteria( and should be obtained within 28 days prior to registration): Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L, Platelets≥ 90 x 109/L, Hemoglobin ≥ 90 g/L Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≤2.5 x ULN without liver metastasis,≤ 5 x ULN with liver metastases Serum BUN and creatinine ≤ 1.5 x Upper Limit of Normal (ULN) Time interval from chemotherapy was more than 2 weeks, endocrine therapy and anti-Her2 targeted treatment are allowed to be used concurrently with FSRT Signed the informed consent form prior to patient entry Exclusion Criteria: Leptomeningeal or hemorrhagic metastases Uncontrolled epilepsy Severe complication: cardiovascular disease, end-stage renal disease, severe hepatic disease, infection etc. Pregnancy or lactation period， women of child-bearing age who are unwilling to accept contraceptive measures. Inability to complete enhanced MRI Patients who are difficult or unable to be followed-up Not suitable for inclusion for specific reasons judged by sponsor Patients who are receiving cytotoxic drug concomitantly Have received prior radiotherapy for brain metastasis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FSRT<br>3 to 5 fractions and 8Gy per fraction will be used for breast cancer patients with 1-10 brain metastases based on the lesion number and volume. | Radiation: Fractionated stereotactic radiotherapy(FSRT)<br>* 3 to 5 fractions and 8Gy per fraction will be used for breast cancer patients with 1-10 brain metastases based on the lesion number and volume.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| intracranial local tumor control rate |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intracranial distant metastasis rate | intracranial distant metastasis after FSRT will be determined by the development of intracranial distant metastasis is determined by new lesions outside of the irradiated area. | 2 years | 
| Intracranial Progression-Free Survival (PFS) | Time from the date of radiotherapy to the investigator-determined date of progression or death due to any cause, whichever occurs first | 2 years | 
| overall survival(OS) | time from the date of informed consent until to the date of death, regardless of the cause of death. | 3 years | 
| Adverse events | AEs were graded according to the National Cancer Institute's Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0.3 | 2 years |