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 August 2014 by University of Washington
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Washington
ClinicalTrials.gov Identifier:
NCT01816035
First received: March 19, 2013
Last updated: August 18, 2014
Last verified: August 2014

March 19, 2013
August 18, 2014
June 2014
February 2016   (final data collection date for primary outcome measure)
  • Thrombokinetic changes [ Time Frame: Baseline up to 30 days ] [ Designated as safety issue: Yes ]
    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.
  • Platelet function, measured using a bleeding time test [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
  • Thrombokinetic changes in the bone marrow [ Time Frame: Baseline up to 22 days ] [ Designated as safety issue: Yes ]
    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.
  • Megakaryocyte toxicity and depletion in bone marrow as assessed by NCI CTCAE v4.0 [ Time Frame: Up to day 42 ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01816035 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: Yes ]
  • Incidence, type, and severity of serious AEs graded according to the NCI CTCAE v4.0 [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Incidence of abnormal laboratory values [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: No ]
  • LVEF [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Death [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Cause of death [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Objective response rate, based on investigator assessment using RECIST v. 1.1 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Objective response rate (ORR), based on investigator assessment using RECIST v. 1.1 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Duration of objective response (DOR), 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 ] [ Designated as safety issue: No ]
  • Clinical benefit rate, defined as the proportion of patients who achieve an objective response (complete response [CR] or partial response [PR]), or maintain SD for at least 6 months from study entry, based on investigator assessment using RECIST v. 1.1 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Ado-Trastuzumab Emtansine in Treating Patients With HER2-Positive Metastatic or Locally Advanced Breast Cancer That Cannot Be Removed by Surgery
Thrombokinetic Studies of Ado-Trastuzumab Emtansine

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 metastatic or locally advanced breast cancer that 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.

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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.

OUTLINE:

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.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HER2-positive Breast Cancer
  • Recurrent Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer
  • Stage IV Breast Cancer
  • Biological: ado-trastuzumab emtansine
    Given IV
    Other Names:
    • Kadcyla
    • T-DM1
    • trastuzumab-DM1
    • trastuzumab-MCC-DM1
    • trastuzumab-MCC-DM1 antibody-drug conjugate
  • Other: laboratory biomarker analysis
    Correlative studies
  • Other: pharmacological study
    Correlative studies
    Other Name: pharmacological studies
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.
Interventions:
  • Biological: ado-trastuzumab emtansine
  • Other: laboratory biomarker analysis
  • Other: pharmacological study
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
20
Not Provided
February 2016   (final data collection date for primary outcome measure)

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 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
Both
18 Years and older
No
United States
 
NCT01816035
7900, NCI-2013-00552, 7900, P30CA015704
No
University of Washington
University of Washington
National Cancer Institute (NCI)
Principal Investigator: Vijayakrishna Gadi Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
University of Washington
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP