Clinical Trials /

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

NCT02571530

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Super-selective <span class="go-doc-concept go-doc-intervention">Intra-arterial Cerebral Infusion of Trastuzumab</span> for the Treatment of Cerebral Metastases of <span class="go-doc-concept go-doc-biomarker">HER2</span>/Neu Positive <span class="go-doc-concept go-doc-disease">Breast Cancer</span>

Title

  • 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
  • Clinical Trial IDs

    NCT ID: NCT02571530

    ORG ID: 15-312

    Trial Conditions

    Neoplasm Metastasis

    Trial Interventions

    Drug Synonyms Arms
    Intra-arterial Cerebral Infusion of Trastuzumab Intra-arterial Cerebral Infusion of Trastuzumab

    Trial Purpose

    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.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Intra-arterial Cerebral Infusion of Trastuzumab Experimental Super-selective Intra-arterial Cerebral Infusion of Trastuzumab After Blood-Brain Barrier Disruption Intra-arterial Cerebral Infusion of Trastuzumab

    Eligibility Criteria

    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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Maximum tolerated dose (MTD)

    Adverse events and dose-limiting toxicities

    Secondary Outcome Measures

    Response Evaluation Criteria in Solid Tumors (RECIST)

    Overall Survival (OS)

    Intracranial Time to Progression

    Trial Keywords