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

• Sponsor: Northwell Health (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02571530
• Collaborator: (none)
• Enrollment: 2
• Location: 1
• Arm: 1
• Actual Duration (Months): 70
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Neoplasm Metastasis	Drug: Intra-arterial Cerebral Infusion of Trastuzumab	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Aug 1, 2015
• Actual Primary Completion Date: Jun 1, 2021
• Actual Study Completion Date: Jun 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intra-arterial Cerebral Infusion of Trastuzumab Super-selective Intra-arterial Cerebral Infusion of Trastuzumab After Blood-Brain Barrier Disruption	Drug: Intra-arterial Cerebral Infusion of Trastuzumab

Outcome Measures

Primary Outcome Measures

1. Maximum tolerated dose (MTD) [30 days]

   Maximum tolerated dose (MTD) the highest dose at which there are no dose limiting toxicities.

2. Adverse events and dose-limiting toxicities [30 days]

   A dose-limiting toxicity (DLT) will be defined as any grade 3 or 4 NCI Common Toxicity Criteria adverse event (CTCAE V4.0).

Secondary Outcome Measures

1. Response Evaluation Criteria in Solid Tumors (RECIST) [1 year]

   RECIST Criteria

2. Overall Survival (OS) [1 year]

3. Intracranial Time to Progression [1 year]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male and female patients 18 years of age or older

2. Karnofsky Performance Status (KPS) of 70 or higher

3. Capable of giving informed consent or have an acceptable surrogate capable of giving consent of the subject's behalf

4. 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.

5. 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:

1. Age less than 18 years

2. KPS less than 70

3. Brain metastases without history of HER2/neu positive breast cancer

4. Leptomeningeal dissemination of brain metastases

5. Pregnancy or refusal to use contraception during a 3 month period before and 7 month period after Intra-arterial (IA) trastuzumab administration

6. Prior administration of intraarterial trastuzumab

7. Subjects with inadequate baseline Left Ventricular Ejection Fraction (LVEF)

8. Subjects with history of infusion reaction with trastuzumab

9. Subjects who have had blood brain barrier (BBB) disruption with mannitol within 48 hours

10. Subjects with evidence of midline shift or herniation

11. Subjects with resectable brain metastases or whose cerebral tumors are amenable to stereotactic radio-surgery

12. Subjects who have not progressed after therapy for brain metastases

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lenox Hill Brain Tumor Center	New York	New York	United States	10075

Sponsors and Collaborators

• Northwell Health

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: John Boockvar, MD Zucker SOM @Hofstra/Northwell, Professor, Northwell Health
• ClinicalTrials.gov Identifier: NCT02571530
• Other Study ID Numbers: 15-312
• First Posted: Oct 8, 2015
• Last Update Posted: Nov 3, 2021
• Last Verified: Oct 1, 2021

• Additional relevant MeSH terms: Neoplasm Metastasis; Trastuzumab

Study Results

No Results Posted as of Nov 3, 2021