A Study of Trastuzumab Emtansine in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer Who Have Received Prior Anti-HER2 And Chemotherapy-based Treatment

Roche

Status and phase: Completed; Phase 3

Conditions: Breast Cancer

Treatments: Drug: Trastuzumab Emtansine

Study type: Interventional

Funder types: Industry

Identifiers

NCT01702571

MO28231

2012-001628-37 (EudraCT Number)

Details and patient eligibility

About

This two-cohort, open-label, multicenter study will assess the safety, efficacy and tolerability of trastuzumab emtansine in participants with HER2-positive locally advanced breast cancer (LABC) or metastatic breast cancer (mBC) who have received prior anti-HER2 and chemotherapy-based treatment. Participants in Cohort 1 will be drawn from the general participant population; Cohort 2 will include only Asian participants.

Enrollment: 2,185 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• HER2-positive disease determined locally
• Histologically or cytologically confirmed invasive breast cancer
• Prior treatment for breast cancer in the adjuvant, unresectable, locally advanced or metastatic setting must include both chemotherapy, alone or in combination with another agent, and an anti-HER2 agent, alone or in combination with another agent
• Documented progression of incurable, unresectable, LABC, or mBC, defined by the investigator: progression must occur during or after most recent treatment for LABC/mBC or within 6 months of completing adjuvant therapy
• Measurable and/or non-measurable disease
• Left ventricular ejection fraction (LVEF) >/=50% by either echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2
• Adequate organ function
• Use of highly effective contraception as defined by the protocol

Exclusion criteria

• History of treatment with trastuzumab emtansine
• Prior enrollment into a clinical study containing trastuzumab emtansine regardless of having received trastuzumab emtansine or not
• Peripheral neuropathy of Grade >/= 3 per National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) v 4.0
• History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage 1 uterine cancer, synchronous or previously diagnosed HER2-positive breast cancer
• History of receiving any anti-cancer drug/biologic or investigational treatment within 21 days prior to first study treatment except hormone therapy, which can be given up to 7 days prior to first study treatment; recovery of treatment-related toxicity consistent with other eligibility criteria
• History of exposure to cumulative doses of anthracyclines
• History of radiation therapy within 14 days of first study treatment. The participant must have recovered from any resulting acute toxicity (to Grade </=1) prior to first study treatment.
• Metastatic central nervous system (CNS) disease only
• Brain metastases which are symptomatic
• History of a decrease in LVEF to less than (<) 40% or symptomatic congestive heart failure (CHF) with previous trastuzumab treatment
• History of symptomatic CHF (New York Heart Association [NYHA] Classes II-IV) or serious cardiac arrhythmia requiring treatment
• History of myocardial infarction or unstable angina within 6 months of first study treatment
• Current dyspnea at rest due to complications of advanced malignancy or requirement for continuous oxygen therapy
• Current severe, uncontrolled systemic disease (clinically significant cardiovascular, pulmonary, or metabolic disease)
• Pregnancy or lactation
• Currently known active infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus
• History of intolerance (such as Grade 3-4 infusion reaction) or hypersensitivity to trastuzumab or murine proteins or any component of the product

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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2,185 participants in 2 patient groups

Trastuzumab Emtansine (All Participants)

Experimental group

Description:

This cohort will enroll all participants with HER2-positive, unresectable, LABC or mBC who have received prior anti-HER2 and chemotherapy treatment and have progressed on or after the most recent treatment for LABC or mBC, or within 6 months of completing adjuvant therapy. Participants will receive trastuzumab emtansine every 3 weeks until unacceptable toxicity, withdrawal of consent, or disease progression.

Treatment:

Drug: Trastuzumab Emtansine

Trastuzumab Emtansine (Asian Participants)

Experimental group

Description:

This cohort will enroll Asian race participants with HER2-positive, unresectable, LABC or mBC who have received prior anti-HER2 and chemotherapy treatment and have progressed on or after the most recent treatment for LABC or mBC, or within 6 months of completing adjuvant therapy. Participants will receive trastuzumab emtansine every 3 weeks until unacceptable toxicity, withdrawal of consent, or disease progression.

Treatment:

Drug: Trastuzumab Emtansine