A Study of Trastuzumab-Mcc-DM1 Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer

Genentech, Inc.110 enrolled

Overview

Study of trastuzumab emtansine (T-DM1) administered to patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

110

Conditions

Metastatic Breast Cancer

Interventions

Trastuzumab emtansine [Kadcyla]DRUG

Intravenous repeating dose

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Signed study-specific Informed Consent Form(s) * Age ≥ 18 years * Histologically documented breast cancer * HER2-positive disease * Metastatic breast cancer * Disease progression on the last chemotherapy regimen received in the metastatic setting * Prior treatment with an anthracycline, trastuzumab, a taxane, lapatinib, and capecitabine in the neoadjuvant, adjuvant, locally advanced, or metastatic setting and prior treatment with at least two lines of therapy (a line of therapy can be a combination of two agents or single-agent chemotherapy) in the metastatic setting * At least two lines of anti-HER2 therapy must have been given in the metastatic setting as monotherapy or combined with chemotherapy or hormonal therapy. The HER2-targeted agent can include trastuzumab, lapatinib, or an investigational agent with HER2-inhibitory activity. * A minimum of 6 weeks of trastuzumab for the treatment of metastatic disease is required * Patients must have had at least 14 days of exposure in the metastatic setting to lapatinib and capecitabine (given together or separately) unless they were intolerant of lapatinib and/or capecitabine Exclusion Criteria: * Chemotherapy ≤ 21 days before enrollment * Trastuzumab ≤ 21 days before enrollment * Hormone therapy ≤ 7 days before enrollment * Granulocyte-stimulating agent \< 14 days before enrollment * Investigational therapy ≤ 28 days before enrollment * Previous radiotherapy for treatment of metastatic breast cancer ≤ 21 days before enrollment * Brain metastases that are untreated, symptomatic, or require therapy to control symptoms; or any radiation, surgery, or other therapy to control symptoms from brain metastases within 3 months of the first study treatment * History of intolerance (including Grade 3-4 infusion reaction) or hypersensitivity to trastuzumab or murine proteins * History of exposure to the following cumulative doses of anthracyclines: Doxorubicin or liposomal doxorubicin \> 500 mg/m\^2; Epirubicin \> 900 mg/m\^2; Mitoxantrone \> 120 mg/m\^2 and idarubicin \> 90 mg/m\^2 * Peripheral neuropathy of Grade ≥ 3 per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0 * History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma * Current unstable angina * History of symptomatic congestive heart failure (CHF), or ventricular arrhythmia requiring treatment * History of myocardial infarction within 6 months of enrollment * Left ventricular ejection fraction (LVEF) \< 50% within 28 days of enrollment * History of decreased LVEF to \< 50% or symptomatic CHF with previous adjuvant 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) * 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 infection with human immunodeficiency virus (HIV), active hepatitis B, and/or hepatitis C virus * Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol

Outcomes

Primary Outcomes

Percentage of Participants With an Objective Response as Assessed Through Independent Radiologic Review

Objective response was defined as a complete response (CR) or partial response (PR) determined on two consecutive occasions ≥ 4 weeks apart, assessed using Response Evaluation Criteria in Solid Tumors (RECIST). CR: the disappearance of all target lesions and all nontarget lesions and normalization of tumor marker level and no new lesions. PR: disappearance of all target lesions and persistence of ≥ 1 nontarget lesion(s) and/or the maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diameter of target lesions, and no new lesions or unequivocal progression of existing nontarget lesions. The primary data cut-off date was 17 September 2009 (approximately 6 months after the last patient was enrolled). The final efficacy analysis was performed using a data cut-off date of 1 January 2010 (approximately 9 months after the last patient was enrolled).

Time frame: From randomization until the primary analysis data cut-off date of September 2009 (6 months after last patient enrolled) and until the final efficacy analysis cut-off date of 1 January 2010 (approximately 9 months after the last patient enrolled).

Secondary Outcomes

Duration of Objective Response as Assessed Through Independent Radiologic Review

For participants who achieved an objective response, duration of objective response was defined as the time from the first tumor assessment that supported a participant's objective response to the time of disease progression or death on study (i.e., death from any cause within 30 days of the last dose of study drug), whichever occurred first. Response was assessed by the independent review facility. Disease progression was at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions or the appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions. For participants who experienced no disease progression and did not die while on study, data were censored at the date of the last tumor assessment. Kaplan-Meier methodology was used to estimate the duration of objective response.

Data from ClinicalTrials.gov

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