Overview

This trial is active, not recruiting.

Condition breast cancer
Treatments trastuzumab emtansine [kadcyla], lapatinib, capecitabine
Phase phase 3
Targets HER2, AKT, CDK, EGFR, ERK
Sponsor Hoffmann-La Roche
Start date February 2009
End date July 2012
Trial size 991 participants
Trial identifier NCT00829166, BO21977, TDM4370g

Summary

This is a Phase III, randomized, multicenter, international, 2-arm, open-label clinical trial designed to compare the safety and efficacy of trastuzumab emtansine (T-DM1) with that of capecitabine + lapatinib for HER2-positive metastatic breast cancer (MBC). Patients were treated until disease progression, unmanageable toxicity, or study termination. Once disease progression was reported, all patients were followed for survival every 3 months until death, loss to follow-up, withdrawal of consent, or study termination.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients received trastuzumab emtansine 3.6 mg/kg intravenously (IV) over 30-90 minutes on Day 1 of each 21-day treatment cycle.
trastuzumab emtansine [kadcyla] T-DM1
Trastuzumab emtansine was provided as a single-use lyophilized formulation.
(Active Comparator)
Patients received lapatinib 1250 mg/day orally once per day of each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle.
lapatinib Tykerb
Lapatinib was available as film-coated tablets.
capecitabine Xeloda
Capecitabine was available as film-coated tablets.

Primary Outcomes

Measure
Progression-free Survival (PFS) Assessed by an Independent Review Committee
time frame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Overall Survival
time frame: From the date of randomization through the data cut-off date of 31 Jul 2012 (up to 3 years, 5 months)
1 and 2 Year Survival
time frame: From the date of randomization through the data cut-off date of 31 Jul 2012 (up to 3 years, 5 months)

Secondary Outcomes

Measure
Progression-free Survival (PFS) Assessed by the Investigator
time frame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Objective Response (OR) Assessed by the Independent Review Committee
time frame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Duration of Objective Response (OR)
time frame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Clinical Benefit
time frame: 6 months after randomization
Time to Treatment Failure
time frame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Time to Symptom Progression
time frame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - (Human epidermal growth factor receptor 2 (HER2) status must be prospectively, centrally tested and be HER2-positive based on central laboratory assay results. - Histologically or cytologically confirmed invasive breast cancer. - Prior treatment for breast cancer in the adjuvant, unresectable, locally advanced, or metastatic setting must include both a taxane, alone or in combination with another agent, and trastuzumab, alone or in combination with another agent. - Documented progression of incurable, unresectable, locally advanced or metastatic breast cancer, defined by the investigator. - Measurable and/or nonmeasurable disease; patients with central nervous system (CNS)-only disease are excluded. - Cardiac ejection fraction ≥ 50% by either echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan. - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. - For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective, non-hormonal form of contraception; contraception use should continue for the duration of the study treatment and for at least 6 months after the last dose of study treatment. Exclusion Criteria: - History of treatment with trastuzumab emtansine (T-DM1). - Prior treatment with lapatinib or capecitabine. - Peripheral neuropathy of Grade ≥ 3 per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3.0. - History of other malignancy within the last 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, or cancers with a similar curative outcome as those mentioned above. - History of receiving any anti-cancer drug/biologic or investigational treatment within 21 days prior to randomization except hormone therapy, which could be given up to 7 days prior to randomization; recovery of treatment-related toxicity consistent with other eligibility criteria. - History of radiation therapy within 14 days of randomization. - Brain metastases that are untreated, symptomatic, or require therapy to control symptoms, as well as any history of radiation, surgery, or other therapy, including steroids, to control symptoms from brain metastases within 2 months (60 days) of randomization. - History of symptomatic congestive heart failure (CHF) or serious cardiac arrhythmia requiring treatment. - History of myocardial infarction or unstable angina within 6 months of randomization. - Current dyspnea at rest due to complications of advanced malignancy or current requirement for continuous oxygen therapy. - Current severe, uncontrolled systemic disease (eg, clinically significant cardiovascular, pulmonary, or metabolic disease). - Pregnancy or lactation. - Current known active infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus. - Presence of conditions that could affect gastrointestinal absorption: Malabsorption syndrome, resection of the small bowel or stomach, and ulcerative colitis. - History of intolerance (such as Grade 3-4 infusion reaction) to trastuzumab. - Known hypersensitivity to 5-fluorouracil or known dihydropyrimidine dehydrogenase deficiency. - Current treatment with sorivudine or its chemically related analogs, such as brivudine.

Additional Information

Official title A Randomized, Multicenter, Phase III Open-label Study of the Efficacy and Safety of Trastuzumab Emtansine vs. Capecitabine + Lapatinib in Patients With HER2-positive Locally Advanced or Metastatic Breast Cancer Who Have Received Prior Trastuzumab-based Therapy
Trial information was received from ClinicalTrials.gov and was last updated in April 2015.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.