A randomized, multicenter, phase III open-label study of the efficacy and safety of trastuzumab-MCC-DM1 vs. capecitabine + lapatinib in patients with HER2-positive locally advanced or metastatic breast cancer who have received prior trastuzumab-based therapy - EMILIA
- Conditions
- Treatment of patients with HER2-positive locally advanced or metastatic breast cancer with progressive disease who have previously received a taxane and trastuzumab.MedDRA version: 9.1Level: LLTClassification code 10027475Term: Metastatic breast cancerMedDRA version: 9.1Level: LLTClassification code 10065430Term: HER-2 positive breast cancer
- Registration Number
- EUCTR2008-005713-22-FR
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 991
a. Disease-Specific Criteria
1. HER2 status must be prospectively, centrally tested and be HER2-positive (i.e., IHC 3+ and/or gene-amplified by FISH) based on central laboratory assay results for this study to be eligible for enrollment.
2. Histologically or cytologically confirmed invasive breast cancer (incurable locally advanced or metastatic disease)
3. Prior treatment for breast cancer must include both: A taxane, alone or in combination with another agent, and Trastuzumab in the adjuvant, locally advanced, or metastatic setting
4. Documented progression of incurable locally advanced or metastatic breast cancer, defined by the investigator Progression must occur during or after treatment for advanced or metastatic disease or within 6 months of completing adjuvant therapy.
5. Measurable and/or nonmeasurable disease
b. General Criteria
6. Age =18 years
7. Cardiac ejection fraction =50% by either ECHO or MUGA
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
9. Adequate organ function, evidenced by the following laboratory results within 2 weeks prior to randomization:
Absolute neutrophil count >1500 cells/mm3
Platelet count > 100,000 cells/mm3
Hemoglobin >9.0 g/dL. Patients are allowed to be transfused red blood cells to this level.
Albumin =2.5 g/dL
Total bilirubin =1.5 upper limit of normal (ULN)
SGOT (AST), SGPT (ALT), and alkaline phosphatase =2.5 ×ULN with the following exception:
Patients with bone metastases: alkaline phosphatase =5 ×ULN
Creatinine clearance >50 mL/min based on Cockroft-Gault glomerular filtration rate (GFR) estimation:
(140 -Age) ×(weight in kg) ×(0.85 if female)/72 ×serum creatinine
International normalized ratio (INR) and activated partial thromboplastin time (aPTT) <1.5 ×ULN (unless on therapeutic coagulation)
•For women of childbearing potential, agreement to use an effective form of contraception (patient and/or partner, e.g., surgical sterilization, two reliable barrier methods, birth control pills, or contraceptive hormone implants) and to continue its use for the duration of the study according to local health authority guidelines
Specific country requirements will be followed (e.g., in the United Kingdom, women of childbearing potential and male subjects and their partners of childbearing potential must use two methods of contraception [one of which must be a barrier method] for the duration of the study).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
a. Cancer-Related Criteria
1. History of treatment with T-DM1
2. Prior treatment with lapatinib or capecitabine.
3. Peripheral neuropathy of Grade = 3 per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3.0
4. 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 outcome as those mentioned above.
5. History of receiving any chemotherapy or investigational treatment within 21 days prior to randomization and recovery of treatment-related toxicity consistent with other eligibility criteria
6. History of radiation therapy within 14 days of randomization
If the patient has a history of recent radiation therapy, the patient must have recovered from any resulting acute toxicity (to Grade = 1) prior to randomization.
7. Brain metastases that are untreated, symptomatic, or require therapy to control symptoms; or any radiation, surgery, or other therapy, including steroids, to control symptoms from brain metastases within 2 months of randomization
b. Cardiopulmonary Function
8. History of symptomatic CHF or ventricular arrhythmia requiring treatment
9. History of myocardial infarction or unstable angina within 6 months of randomization
10. Severe dyspnea at rest due to complications of advanced malignancy or current requirement for continuous oxygen therapy
c. General Criteria
11. Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease)
12. Pregnancy or lactation
13. Current known active infection with HIV, hepatitis B virus, or hepatitis C virus
14. Presence of conditions that could affect gastrointestinal absorption: malabsorption syndrome, resection of the small bowel or stomach, and ulcerative colitis
15. History of intolerance (such as Grade 3-4 infusion reaction) to trastuzumab
16. Known hypersensitivity to 5-fluorouracil or known dihydropyrimidine dehydrogenase deficiency
17. Current treatment with sorivudine or its chemically related analogs, such as brivudine
18. Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol (i.e., unable to swallow pills)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method