An Open-label Study of Trastuzumab Emtansine (T-DM1) vs Capecitabine + Lapatinib in Patients With HER2-positive Locally Advanced or Metastatic Breast Cancer

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIITreatmentClosed18 and overPharmaceutical / IndustryBO21977
TDM4370g, NCT00829166

Trial Description


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.

Eligibility Criteria

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.

Trial Contact Information

Trial Lead Organizations/Sponsors

F. Hoffmann - La Roche, Limited

    Clinical Trials, Study Director

    Link to the current record.
    NLM Identifier NCT00829166 processed this data on May 27, 2015

    Note: Information about this trial is from the database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the record to standardize the names of study sponsors, sites, and contacts. only lists sites that are recruiting patients for active trials, whereas lists all sites for all trials. Questions and comments regarding the presented information should be directed to