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

NCT01816035 | Completed Phase 1

• 4 other identifiers: 7900NCI-2013-00552CC-7900P30CA015704
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Platelet function, measured using a bleeding time test

  Up to 30 days

• Thrombokinetic changes

  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.

  Baseline up to 30 days

Secondary Outcomes (9)

• Cause of death

  Up to 2 years

• Clinical benefit rate

  Up to 2 years

• Death

  Up to 2 years

• Incidence of abnormal laboratory values

  Up to 30 days after completion of study treatment

• 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

  Up to 30 days after completion of study treatment

Study Arms (1)

Treatment (trastuzumab emtansine)

EXPERIMENTAL

Patients 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.

Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Biological: Trastuzumab Emtansine

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (trastuzumab emtansine)

Pharmacological Study OTHER

Correlative studies

Treatment (trastuzumab emtansine)

Trastuzumab Emtansine BIOLOGICAL

Given IV

Also known as: Ado Trastuzumab Emtansine, Kadcyla, PRO132365, RO5304020, T-DM1, Trastuzumab-DM1, Trastuzumab-MCC-DM1, Trastuzumab-MCC-DM1 Antibody-Drug Conjugate, Trastuzumab-MCC-DM1 Immunoconjugate

Treatment (trastuzumab emtansine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Trastuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Vijayakrishna Gadi

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2013
• First Posted: March 21, 2013
• Study Start: June 1, 2014
• Primary Completion: December 1, 2016
• Study Completion: April 1, 2017
• Last Updated: May 23, 2017

Record last verified: 2017-05

Locations

US (1)