Clinical Trials /

Trastuzumab Emtansine in Treating Patients With HER2-Positive Metastatic or Locally Advanced Breast Cancer That Cannot Be Removed by Surgery

NCT01816035

Description:

This phase I trial studies the side effects and best way of giving trastuzumab emtansine in treating patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer that has spread to other parts of the body or nearby tissue and cannot be removed by surgery. Biological therapies, such as trastuzumab emtansine, may stimulate the immune system in different ways and stop cancer cells from growing.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Trastuzumab Emtansine in Treating Patients With HER2-Positive Metastatic or Locally Advanced Breast Cancer That Cannot Be Removed by Surgery
  • Official Title: Thrombokinetic Studies of Ado-Trastuzumab Emtansine

Clinical Trial IDs

  • ORG STUDY ID: 7900
  • SECONDARY ID: NCI-2013-00552
  • SECONDARY ID: CC-7900
  • SECONDARY ID: 7900
  • SECONDARY ID: P30CA015704
  • NCT ID: NCT01816035

Conditions

  • HER2/Neu Positive
  • Recurrent Breast Carcinoma
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer
  • Stage IV Breast Cancer

Interventions

DrugSynonymsArms
Trastuzumab EmtansineAdo Trastuzumab Emtansine, Kadcyla, PRO132365, RO5304020, T-DM1, Trastuzumab-DM1, Trastuzumab-MCC-DM1, Trastuzumab-MCC-DM1 Antibody-Drug Conjugate, Trastuzumab-MCC-DM1 ImmunoconjugateTreatment (trastuzumab emtansine)

Purpose

This phase I trial studies the side effects and best way of giving trastuzumab emtansine in treating patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer that has spread to other parts of the body or nearby tissue and cannot be removed by surgery. Biological therapies, such as trastuzumab emtansine, may stimulate the immune system in different ways and stop cancer cells from growing.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess change in thrombokinetics (platelet circulation life span).

      SECONDARY OBJECTIVES:

      I. Benefit rate (as defined by stable disease, partial response, or complete response by
      Response Evaluation Criteria in Solid Tumors [RECIST] v 1.1) at the end of study activities.

      II. To evaluate the safety of trastuzumab emtansine (ado-trastuzumab emtansine) (non-platelet
      toxicity).

      III. To evaluate the pharmacokinetics of ado-trastuzumab emtansine.

      OUTLINE:

      Patients receive trastuzumab emtansine intravenously (IV) over 30-90 minutes on day 1.
      Treatment repeats every 21 days for 3 courses in the absence of disease progression or
      unacceptable toxicity. Patients achieving response may continue treatment.

      After completion of study treatment, patients are followed up periodically.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (trastuzumab emtansine)ExperimentalPatients receive trastuzumab emtansine IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients achieving response may continue treatment.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Signed study-specific informed consent form
    
              -  Histologically or cytologically documented breast cancer
    
              -  Metastatic or unresectable locally advanced/recurrent breast cancer
    
              -  HER2-positive disease documented as in situ hybridization (ISH)-positive and/or 3+ by
                 immunohistochemistry (IHC) on previously collected tumor tissue
    
              -  Absolute neutrophil count (ANC) > 1500 cells/mm^3
    
              -  Platelet count > 100,000/mm^3
    
              -  Hemoglobin > 9.0 g/dL (patients are allowed to receive transfused red blood cells
                 [RBC] to achieve this level)
    
              -  Total bilirubin =< 1.5 × upper limit of normal (ULN), except in patients with
                 previously documented Gilbert's syndrome, in which case the direct bilirubin should be
                 less than or equal to the ULN
    
              -  Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
                 serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 ×
                 ULN
    
              -  Alkaline phosphatase =< 2.5 × ULN (patients with hepatic and/or bone metastases:
                 alkaline phosphatase =< 5 × ULN)
    
              -  Serum creatinine < 1.5 × ULN
    
              -  International normalized ratio (INR) < 1.5 × ULN
    
              -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
    
              -  Left ventricular ejection fraction (LVEF) >= 50% by either echocardiogram (ECHO) or
                 multigated acquisition scan (MUGA)
    
              -  Negative results of serum pregnancy test for premenopausal women of reproductive
                 capacity and for women < 12 months after entering menopause
    
              -  For women of childbearing potential and men with partners of childbearing potential,
                 agreement by the patient and/or partner to use a highly effective, non-hormonal form
                 of contraception or two effective forms of non-hormonal contraception; female patients
                 of childbearing potential must agree to use two effective forms of non-hormonal
                 contraception; effective methods of contraception include: intrauterine device (IUD);
                 female condom; male condom; diaphragm with spermicide; cervical cap; or a sterile
                 sexual partner; male patients with partners of childbearing potential must use barrier
                 contraception; in addition, male patients should also have their partners use another
                 method of contraception from the time of informed consent through the duration of
                 study activity
    
              -  Willingness and ability to comply with scheduled visits, treatment plans, laboratory
                 tests, and other study procedures, including thrombokinetic studies and platelet
                 function studies
    
            Exclusion Criteria:
    
            CANCER-RELATED CRITERIA
    
              -  Known platelet disorder, such as von Willebrand's disease or baseline platelet count
                 of < 100,000/mm^3
    
              -  Chemotherapy =< 21 days before first study treatment
    
              -  Trastuzumab =< 21 days before first study treatment
    
              -  Lapatinib =< 14 days before first study treatment
    
              -  Investigational therapy or any other therapy =< 28 days before first study treatment
    
              -  Any prior ado-trastuzumab emtansine
    
              -  Previous radiotherapy for the treatment of unresectable, locally advanced/recurrent or
                 metastatic breast cancer is not allowed if:
    
                   -  The last fraction of radiotherapy has been administered within 14 days of first
                      on-study thormbokinetic study
    
                   -  The patient has not recovered from any resulting acute toxicity (to grade =< 1)
                      prior to first on-study thormbokinetic study
    
              -  Brain metastases that are untreated or symptomatic, or require any radiation, surgery,
                 or steroid therapy to control symptoms from brain metastases within 14 days of first
                 on-study thrombokinetic study; for patients with newly diagnosed brain metastases or
                 unequivocal progression of brain metastases on screening scans, localized treatment
                 (i.e., surgery, radiosurgery, and/or whole brain radiotherapy) is required before
                 study enrollment; subjects with known brain metastases must have clinically controlled
                 neurologic symptoms, defined as surgical excision and/or radiation therapy followed by
                 14 days of stable neurologic function prior to the first thrombokinetic procedure;
                 patients with small brain metastases not symptomatic and deemed requiring treatment by
                 managing clinicians or study investigators may be permitted to enroll on study
    
              -  History of intolerance (including grade 3 or 4 infusion reaction) or hypersensitivity
                 to trastuzumab or murine proteins
    
              -  Current peripheral neuropathy of grade >= 3 per the National Cancer Institute Common
                 Terminology Criteria for Adverse Events (NCI CTCAE) v. 4.0
    
              -  Current use of any platelet functioning inhibitors (including aspirin) within 14 days
                 of first on-study thrombokinetic study
    
            CARDIOPULMONARY FUNCTION CRITERIA
    
              -  Current unstable ventricular arrhythmia requiring treatment
    
              -  History of symptomatic congestive heart failure (CHF) (New York Heart Association
                 [NYHA] classes II−IV)
    
              -  History of myocardial infarction or unstable angina within 6 months of enrollment
    
              -  History of a decrease in LVEF to < 40% or symptomatic CHF with previous trastuzumab
                 treatment
    
              -  Severe dyspnea at rest due to complications of advanced malignancy or requiring
                 current continuous oxygen therapy
    
            GENERAL CRITERIA
    
              -  Current severe, uncontrolled non-cancer systemic disease (e.g., clinically significant
                 cardiovascular, pulmonary, or metabolic disease) resulting in a life expectancy of < 6
                 months
    
              -  Major surgical procedure or significant traumatic injury within 28 days before
                 enrollment or anticipation of the need for major surgery during the course of study
                 treatment
    
              -  Current pregnancy or lactation
    
              -  Current known active infection with human immunodeficiency virus (HIV), hepatitis B,
                 and/or hepatitis C virus; for patients who are known carriers of hepatitis B virus
                 (HBV), active hepatitis B infection must be ruled out based on negative serologic
                 testing and/or determination of HBV deoxyribonucleic acid (DNA) viral load per local
                 guidelines
    
              -  Assessed by the investigator to be unable or unwilling to comply with the requirements
                 of the protocol
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Platelet function, measured using a bleeding time test
    Time Frame:Up to 30 days
    Safety Issue:
    Description:The actual analysis will fit a linear mixed effects model, using a two-sided Wald test to compare pre-therapy to the two post-therapy values, and should have greater power than a matched pairs design. Also, platelet lifespan may be measured in absolute terms (platelet lifespan) or relative terms (percentage relative to pre-therapy lifespan), and may be transformed to decrease the influence of extreme values.

    Secondary Outcome Measures

    Measure:Cause of death
    Time Frame:Up to 2 years
    Safety Issue:
    Description:
    Measure:Clinical benefit rate
    Time Frame:Up to 2 years
    Safety Issue:
    Description:Defined as the proportion of patients who achieve an objective response (complete response or stable disease) based on investigator assessment using Response Evaluation Criteria in Solid Tumors version 1.1 criteria at the conclusion of study procedures.
    Measure:Death
    Time Frame:Up to 2 years
    Safety Issue:
    Description:
    Measure:Incidence of abnormal laboratory values
    Time Frame:Up to 30 days after completion of study treatment
    Safety Issue:
    Description:
    Measure:Incidence of adverse events leading to study treatment discontinuation, modification, or interruption, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
    Time Frame:Up to 30 days after completion of study treatment
    Safety Issue:
    Description:
    Measure:Incidence, type, and severity of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
    Time Frame:Up to 30 days after completion of study treatment
    Safety Issue:
    Description:
    Measure:Incidence, type, and severity of severe adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
    Time Frame:Up to 30 days after completion of study treatment
    Safety Issue:
    Description:
    Measure:Left ventricular ejection fraction
    Time Frame:Up to 2 years
    Safety Issue:
    Description:
    Measure:Objective response rate, based on investigator assessment using Response Evaluation Criteria in Solid Tumors version 1.1
    Time Frame:Up to 2 years
    Safety Issue:
    Description:

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Completed
    Lead Sponsor:University of Washington

    Last Updated

    May 19, 2017