Clinical trial NCT00679211: A Study of Trastuzumab-Mcc-DM1 Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer
Official title: A Phase II, Single-Arm, Open-Label Study of Trastuzumab-Mcc-DM1 Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Keywords: HER2-positive breast cancer
HER2
MBC
Trastuzumab emtansine
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2008-05-16
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With an Objective Response as Assessed Through Independent Radiologic Review
timeFrame: 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:
measure: Duration of Objective Response as Assessed Through Independent Radiologic Review
timeFrame: From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.
measure: Progression-free Survival as Assessed Through Independent Radiologic Review
timeFrame: From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.
measure: Percentage of Participants With Clinical Benefit Based on Independent Radiologic Review
timeFrame: From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.
measure: Objective Response Based on Investigator Assessment
timeFrame: From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.
measure: Progression-free Survival Based on Investigator Assessment
timeFrame: From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.
measure: Duration of Objective Response Based on Investigator Assessment
timeFrame: From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.
measure: Percentage of Participants With Clinical Benefit Based on Investigator Assessment
timeFrame: From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.
Other outcomes:
Locations:
Study officials:
affiliation: Genentech, Inc.
name: Ellie Guardino, M.D., PhD.
role: STUDY_DIRECTOR
References: