Phase 2
Completed N=137
A Study of the Efficacy and Safety of Trastuzumab Emtansine (Trastuzumab-MCC-DM1) vs. Trastuzumab (Herceptin®) and Docetaxel (Taxotere®) in Patients With Metastatic HER2-positive Breast Cancer Who Have Not Received Prior Chemotherapy for Metastatic Disease
Source: ClinicalTrials.gov NCT00679341 ↗Enrolled (actual)
137
Serious AEs
23.0%
Results posted
May 2013
Primary outcomePrimary: Progression-free Survival (PFS) by the Investigator Using Modified Response Evaluation Criteria In Solid Tumors (RECIST) — 14.2; 9.2 Months
Summary
This was a Phase II, randomized, multicenter, international, 2-arm, open-label clinical trial designed to explore the efficacy and safety of trastuzumab emtansine (T-DM1) relative to the combination of trastuzumab and docetaxel in patients with human epidermal growth factor receptor 2 (HER2)-positive, unresectable, locally advanced breast cancer and/or metastatic breast cancer who have not received prior chemotherapy for metastatic disease.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression-free Survival (PFS) by the Investigator Using Modified Response Evaluation Criteria In Solid Tumors (RECIST) |
14.2; 9.2 | — |
| SECONDARY Overall Survival |
NA; NA | — |
| SECONDARY Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) |
64.2; 58.0 | — |
| SECONDARY Duration of Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) |
NA; 9.5 | — |
| SECONDARY Clinical Benefit (CB) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) |
74.6; 81.2 | — |
| SECONDARY Time to Symptom Progression |
7.5; 3.5 | — |
| SECONDARY Serum Concentrations (Area Under the Concentration-time Curve [AUC]) of Trastuzumab Emtansine and Total Trastuzumab |
495; 473; 700; 788 | — |
| SECONDARY Plasma Concentration of Free Emtansine |
5.11; 4.71 | — |
Eligibility Criteria
Inclusion Criteria
- Histologically or cytologically confirmed adenocarcinoma of the breast with locally advanced or metastatic disease, and a candidate for chemotherapy.
- Human epidermal growth factor receptor 2 (HER2)-positive.
- No prior chemotherapy for their metastatic breast cancer (MBC).
- Measurable disease.
- Age ≥ 18 years.
- For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective, non-hormonal form of contraception or 2 effective forms of non-hormonal contraception by the patient and/or partner. Contraception use must continue for the duration of study treatment and for at least 6 months after the last dose of study treatment. Male patients whose partners are pregnant should use condoms for the duration of the study.
Exclusion Criteria
- History of any chemotherapy for MBC.
- An interval of 500 mg/m^2; epirubicin > 900 mg/m^2; mitoxantrone > 120mg/m^2 and idarubicin > 90 mg/m^2.
- Current unstable angina.
- History of symptomatic congestive heart failure, or ventricular arrhythmia requiring treatment.
- History of myocardial infarction within 6 months prior to randomization.
- Left ventricular ejection fraction (LVEF) below 50% within approximately 28 days prior to randomization.
- History of decreased LVEF or symptomatic congestive heart failure (CHF) with previous adjuvant trastuzumab treatment.
- Cardiac troponin I ≥ 0.2 ng/mL within 28 days of randomization.
- Severe dyspnea at rest because of complications of advanced malignancy or requiring current continuous oxygen therapy.
- Current severe, uncontrolled systemic disease (eg, clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures).
- Major surgical procedure or significant traumatic injury within approximately 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment.
- Current pregnancy or lactation.
- History of receiving any investigational treatment within approximately 28 days prior to randomization.
- Current known infection with human immunodeficiency virus (HIV), active hepatitis B and/or hepatitis C virus.
- History of intolerance (including Grade 3-4 infusion reaction) or hypersensitivity to trastuzumab, murine proteins, or docetaxel.
- Known hypersensitivity to any of the study drugs, including the excipients, or any drugs formulated in polysorbate 80.
- Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.
Data sourced from ClinicalTrials.gov (NCT00679341). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.