Super-selective Intra-arterial Cerebral Infusion of Trastuzumab for the Treatment of Cerebral Metastases of HER2/Neu Positive Breast Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety of administering a single dose of trastuzumab into the artery for the treatment of brain metastasis(es) from HER2/neu positive breast cancer. This study will try to determine the best tolerated single dosage of trastuzumab administered into arteries by gradually increasing the dosage given to participants as the study progresses. Early participants will receive a dosage of 1 mg/kg. As more participants enroll into the study, this single dosage will be increased at designated levels up to 8 mg/kg, if it's determined to be safe to increase. Trastuzumab is a type of antibody, which is a protein used by the body's immune system to fight against pathogens such as bacteria and viruses. This antibody binds to cell receptors known as the HER2/neu tyrosine kinase receptor. These receptors are expressed in certain cancer subtypes such as breast cancer. By blocking signaling through this HER2/neu receptor, trastuzumab can slow down or stop the over-expression of the HER2/neu protein. Over-expression of HER2/neu has been shown to play a role in the development and progression of certain types of breast cancer. Therefore, by slowing down or stopping the expression of HER2/neu, investigators hope to slow down or stop the growth of metastasis(es) and increase the responsiveness to therapy.

Official Title
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Phase 1 Trial of Super-selective Intra-arterial Cerebral Infusion of Trastuzumab After Blood-Brain Barrier Disruption for the Treatment of Cerebral Metastases of HER2/Neu Positive Breast Cancer

Conditions
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Neoplasm Metastasis

Intervention / Treatment
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* Drug: Intra-arterial Cerebral Infusion of Trastuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients 18 years of age or older Karnofsky Performance Status (KPS) of 70 or higher Capable of giving informed consent or have an acceptable surrogate capable of giving consent of the subject's behalf Have a documented history of HER2/neu positive breast cancer that is 3+ on immunohistochemical staining or positive on fluorescent in-situ hybridization (FISH) or chromogenic in-situ hybridization (CISH) and have evidence of parenchymal metastatic tumor(s) on brain imaging studies. Adequate labs for procedure with trastuzumab, including but not limited to White Blood Count (WBC), Hemoglobin, Hematocrit, Platelet Count, Prothrombin Time (PT), International Normalized Ratio (INR), Sodium, Potassium, Chloride, Glucose, Blood Urea Nitrogen (BUN), Serum Creatinine (CR) Exclusion Criteria: Age less than 18 years KPS less than 70 Brain metastases without history of HER2/neu positive breast cancer Leptomeningeal dissemination of brain metastases Pregnancy or refusal to use contraception during a 3 month period before and 7 month period after Intra-arterial (IA) trastuzumab administration Prior administration of intraarterial trastuzumab Subjects with inadequate baseline Left Ventricular Ejection Fraction (LVEF) Subjects with history of infusion reaction with trastuzumab Subjects who have had blood brain barrier (BBB) disruption with mannitol within 48 hours Subjects with evidence of midline shift or herniation Subjects with resectable brain metastases or whose cerebral tumors are amenable to stereotactic radio-surgery Subjects who have not progressed after therapy for brain metastases

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Intra-arterial Cerebral Infusion of Trastuzumab<br>Super-selective Intra-arterial Cerebral Infusion of Trastuzumab After Blood-Brain Barrier Disruption | Drug: Intra-arterial Cerebral Infusion of Trastuzumab<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) | Maximum tolerated dose (MTD) the highest dose at which there are no dose limiting toxicities. | 30 days | 
| Adverse events and dose-limiting toxicities | A dose-limiting toxicity (DLT) will be defined as any grade 3 or 4 NCI Common Toxicity Criteria adverse event (CTCAE V4.0). | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Evaluation Criteria in Solid Tumors (RECIST) | RECIST Criteria | 1 year | 
| Overall Survival (OS) |  | 1 year | 
| Intracranial Time to Progression |  | 1 year |