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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2016 by University of Washington
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Washington Identifier:
First received: March 19, 2013
Last updated: November 28, 2016
Last verified: November 2016
This phase I trial studies the side effects and best way of giving ado-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 ado-trastuzumab emtansine, may stimulate the immune system in different ways and stop cancer cells from growing.

Condition Intervention Phase
HER2/Neu Positive
Recurrent Breast Carcinoma
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Stage IV Breast Cancer
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Biological: Trastuzumab Emtansine
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Thrombokinetic Studies of Ado-Trastuzumab Emtansine

Resource links provided by NLM:

Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Platelet function, measured using a bleeding time test [ Time Frame: Up to 30 days ]
  • Thrombokinetic changes [ Time Frame: Baseline up to 30 days ]
    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:
  • Cause of death [ Time Frame: Up to 2 years ]
  • Clinical benefit rate, defined as the proportion of patients who achieve an objective response (complete response or partial response), or maintain stable disease for at least 6 months from study entry, based on investigator assessment using RECIST v 1.1 [ Time Frame: Up to 2 years ]
  • Death [ Time Frame: Up to 2 years ]
  • Duration of objective response, based on investigator assessment using RECIST v.1.1 [ Time Frame: First tumor assessment that supports the patient's objective response until the time of disease progression or death from any cause, assessed up to 2 years ]
  • Incidence of abnormal laboratory values [ Time Frame: Up to 30 days after completion of study treatment ]
  • Incidence of AEs leading to study treatment discontinuation, modification, or interruption, graded according to the NCI CTCAE v4.0 [ Time Frame: Up to 30 days after completion of study treatment ]
  • Incidence, type, and severity of adverse events (AEs) graded according to the NCI CTCAE v4.0 [ Time Frame: Up to 30 days after completion of study treatment ]
  • LVEF [ Time Frame: Up to 2 years ]
  • Objective response rate, based on investigator assessment using RECIST v. 1.1 [ Time Frame: Up to 2 years ]
  • PFS assessed using RECIST v. 1.1 [ Time Frame: Time from study entry to the first occurrence of disease progression, or death from any cause, assessed up to 2 years ]

Estimated Enrollment: 20
Study Start Date: June 2014
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (ado-trastuzumab emtansine)
Patients receive ado-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.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
Biological: Trastuzumab Emtansine
Given IV
Other Names:
  • Ado Trastuzumab Emtansine
  • Kadcyla
  • PRO132365
  • T-DM1
  • Trastuzumab-DM1
  • Trastuzumab-MCC-DM1
  • Trastuzumab-MCC-DM1 Antibody-Drug Conjugate
  • Trastuzumab-MCC-DM1 Immunoconjugate

Detailed Description:


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


I. To evaluate the progression free survival (PFS), duration of response, benefit rate (as defined by stable disease, partial response, or complete response by Response Evaluation Criteria in Solid Tumors [RECIST] v 1.1), overall response rate (as defined by partial or complete response by RECIST v 1.1), and survival.

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

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


Patients receive ado-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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
  • 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:

  • 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 prior to randomization
    • The patient has not recovered from any resulting acute toxicity (to grade =< 1) prior to randomization
  • Brain metastases that are untreated or symptomatic, or require any radiation, surgery, or steroid therapy to control symptoms from brain metastases within 30 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 study treatment
  • 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
  • Current severe, uncontrolled 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01816035

United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Breast Oncology Research Team    206-288-6329   
Principal Investigator: Vijayakrishna K. Gadi         
Sponsors and Collaborators
University of Washington
National Cancer Institute (NCI)
Principal Investigator: Vijayakrishna Gadi Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

Responsible Party: University of Washington Identifier: NCT01816035     History of Changes
Other Study ID Numbers: 7900
NCI-2013-00552 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
7900 ( Other Identifier: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium )
P30CA015704 ( US NIH Grant/Contract Award Number )
Study First Received: March 19, 2013
Last Updated: November 28, 2016

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Ado-trastuzumab emtansine
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic processed this record on March 28, 2017