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

NCT02571530 | Terminated Phase 1

• 1 other identifier: 15-312
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Neoplasm Metastasis

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Response Evaluation Criteria in Solid Tumors (RECIST)

  1 year

• Overall Survival (OS)

  1 year

• Intracranial Time to Progression

  1 year

Study Arms (1)

Intra-arterial Cerebral Infusion of Trastuzumab

EXPERIMENTAL

Super-selective Intra-arterial Cerebral Infusion of Trastuzumab After Blood-Brain Barrier Disruption

Drug: Intra-arterial Cerebral Infusion of Trastuzumab

Interventions

Intra-arterial Cerebral Infusion of Trastuzumab DRUG

Intra-arterial Cerebral Infusion of Trastuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Northwell Health: lead

Study Sites (1)

Lenox Hill Brain Tumor Center

New York, New York, 10075, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 16, 2015
• First Posted: October 8, 2015
• Study Start: August 1, 2015
• Primary Completion: June 1, 2021
• Study Completion: June 1, 2021
• Last Updated: November 3, 2021

Record last verified: 2021-10

Locations

US (1)