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Thrombokinetic Studies of Trastuzumab Emtansine

Phase 1
18 Years
Not Enrolling
HER2-positive Breast Cancer, Recurrent Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer, Stage IV Breast Cancer

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Trial Information

Thrombokinetic Studies of Trastuzumab Emtansine


I. To assess change in thrombokinetics (platelet circulation life span) and megakaryopoiesis
effects in bone marrow.


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 trastuzumab emtansine (ado-trastuzumab emtansine)
(non-platelet toxicity).

III. To evaluate the pharmacokinetics of trastuzumab emtansine.


Patients receive trastuzumab emtansine intravenously (IV) over 30-90 minutes on day 1.
Treatment repeats every 21 days for 2 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.

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

- 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 bone marrow biopsy and thrombokinetic

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 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

- 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 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

- 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

- 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

- Assessed by the investigator to be unable or unwilling to comply with the
requirements of the protocol

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Thrombokinetic changes in the bone marrow

Outcome 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.

Outcome Time Frame:

Baseline up to 22 days

Safety Issue:


Principal Investigator

Vijayakrishna Gadi

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium


United States: Food and Drug Administration

Study ID:




Start Date:

March 2013

Completion Date:

Related Keywords:

  • HER2-positive Breast Cancer
  • Recurrent Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer
  • Stage IV Breast Cancer
  • Breast Neoplasms



Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle, Washington  98109