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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00829166




Registration number
NCT00829166
Ethics application status
Date submitted
22/01/2009
Date registered
26/01/2009
Date last updated
31/10/2016

Titles & IDs
Public title
A Study of Trastuzumab Emtansine Versus Capecitabine + Lapatinib in Participants With HER2-positive Locally Advanced or Metastatic Breast Cancer
Scientific title
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
Secondary ID [1] 0 0
TDM4370g
Secondary ID [2] 0 0
BO21977
Universal Trial Number (UTN)
Trial acronym
EMILIA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Trastuzumab emtansine
Treatment: Drugs - Lapatinib
Treatment: Drugs - Capecitabine

Experimental: Trastuzumab emtansine - Participants will receive trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) intravenous (IV) infusion over 30-90 minutes on Day 1 of each 21-day treatment cycle until disease progression (PD) (as assessed by the investigator), unmanageable toxicity, or study termination.

Active comparator: Lapatinib + Capecitabine - Participants will receive lapatinib 1250 mg (five 250 mg tablets) orally once daily during each 21-day cycle + capecitabine 1000 milligrams per square meter (mg/m\^2) orally twice daily on Days 1-14 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination. Eligible participants will cross over to receive trastuzumab emtansine if second interim analysis demonstrates statistically significant overall survival benefit in favor of trastuzumab emtansine.


Treatment: Drugs: Trastuzumab emtansine
Trastuzumab emtansine 3.6 mg/kg IV infusion over 30-90 minutes on Day 1 of each 21-day treatment cycle.

Treatment: Drugs: Lapatinib
Lapatinib 1250 mg (five 250 mg tablets) orally once daily during each 21-day cycle.

Treatment: Drugs: Capecitabine
Capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 21-day treatment cycle.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With PD or Death as Assessed by an Independent Review Committee (IRC)
Timepoint [1] 0 0
From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Primary outcome [2] 0 0
Progression-free Survival (PFS) as Assessed by an IRC (Co-primary Endpoint)
Timepoint [2] 0 0
From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Primary outcome [3] 0 0
Percentage of Participants Who Died: Second Interim Analysis
Timepoint [3] 0 0
From the date of randomization through the data cut-off date of 31 Jul 2012 (up to 3 years, 5 months)
Primary outcome [4] 0 0
Overall Survival: Second Interim Analysis (Co-primary Endpoint)
Timepoint [4] 0 0
From the date of randomization through the data cut-off date of 31 Jul 2012 (up to 3 years, 5 months)
Primary outcome [5] 0 0
Percentage of Participants Who Died: Final Analysis
Timepoint [5] 0 0
From the date of randomization through the data cut-off date of 31 Dec 2014 (up to 5 years, 11 months)
Primary outcome [6] 0 0
Overall Survival: Final Analysis
Timepoint [6] 0 0
From the date of randomization through the data cut-off date of 31 Dec 2014 (up to 5 years, 11 months)
Primary outcome [7] 0 0
Percentage of Participants Who Were Alive at Year 1
Timepoint [7] 0 0
Year 1
Primary outcome [8] 0 0
Percentage of Participants Who Were Alive at Year 2
Timepoint [8] 0 0
Year 2
Secondary outcome [1] 0 0
Percentage of Participants With PD or Death as Assessed by the Investigator
Timepoint [1] 0 0
From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Secondary outcome [2] 0 0
PFS as Assessed by the Investigator
Timepoint [2] 0 0
From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Secondary outcome [3] 0 0
Percentage of Participants With Objective Response (OR) as Assessed by an IRC
Timepoint [3] 0 0
From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Secondary outcome [4] 0 0
Duration of Objective Response (DOR) as Assessed by an IRC
Timepoint [4] 0 0
From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Secondary outcome [5] 0 0
Percentage of Participants With Clinical Benefit as Assessed by an IRC
Timepoint [5] 0 0
From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Secondary outcome [6] 0 0
Percentage of Participants With Treatment Failure
Timepoint [6] 0 0
From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Secondary outcome [7] 0 0
Time to Treatment Failure
Timepoint [7] 0 0
From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Secondary outcome [8] 0 0
Percentage of Participants With Symptom Progression
Timepoint [8] 0 0
From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Secondary outcome [9] 0 0
Time to Symptom Progression
Timepoint [9] 0 0
From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)

Eligibility
Key inclusion criteria
* 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 (which occur during or after most recent treatment or within 6 months after completing of adjuvant therapy) of incurable, unresectable, locally advanced or metastatic breast cancer, defined by the investigator
* Measurable and/or nonmeasurable disease; participants with central nervous system-only disease are excluded
* Cardiac ejection fraction greater than or equal to (>/=) 50 percent (%) by either echocardiogram or multi-gated acquisition 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* History of treatment with trastuzumab emtansine
* 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 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 (for example, 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
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Colorado
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Banja Luka
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Sarajewo
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Brazil
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Belo Horizonte
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Brazil
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Germany
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Weston Super Mare

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Genentech, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.