Back to results

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

Primary Purpose

Neoplasm Metastasis

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Intra-arterial Cerebral Infusion of Trastuzumab

About this trial

This is an interventional treatment trial for Neoplasm Metastasis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Lenox Hill Brain Tumor Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intra-arterial Cerebral Infusion of Trastuzumab

Arm Description

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

Outcomes

Primary Outcome Measures

Maximum tolerated dose (MTD)

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

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).

Secondary Outcome Measures

Response Evaluation Criteria in Solid Tumors (RECIST)

RECIST Criteria

Overall Survival (OS)

Intracranial Time to Progression

Full Information

NCT ID

NCT02571530

First Posted

September 16, 2015

Last Updated

October 27, 2021

Sponsor

Northwell Health

1. Study Identification

Unique Protocol Identification Number

NCT02571530

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2021

Overall Recruitment Status

Terminated

Why Stopped

Low enrollment

Study Start Date

August 2015 (Actual)

Primary Completion Date

June 2021 (Actual)

Study Completion Date

June 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Northwell Health

4. Oversight

Data Monitoring Committee

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neoplasm Metastasis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

2 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Intra-arterial Cerebral Infusion of Trastuzumab

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Intra-arterial Cerebral Infusion of Trastuzumab

Primary Outcome Measure Information:

Title

Maximum tolerated dose (MTD)

Description

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

Time Frame

30 days

Title

Adverse events and dose-limiting toxicities

Description

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

Time Frame

30 days

Secondary Outcome Measure Information:

Title

Response Evaluation Criteria in Solid Tumors (RECIST)

Description

RECIST Criteria

Time Frame

1 year

Title

Overall Survival (OS)

Time Frame

1 year

Title

Intracranial Time to Progression

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Facility Information:

Facility Name

Lenox Hill Brain Tumor Center

City

New York

State/Province

New York

ZIP/Postal Code

10075

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs