Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
drksid header

  DRKS00003643

Trial Description

start of 1:1-Block title

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

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

EMILIA

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

[---]*

end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

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.

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

[---]*

end of 1:1-Block scientific synopsis
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00003643
  •   2012/05/04
  •   2009/01/22
  •   no
  •   [---]*
  •   [---]*
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  •   NCT00829166  (ClinicalTrials.gov)
  •   TDM4370g  (Genentech)
  •   BO21977 
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   Breast Cancer
  •   C50 -  Malignant neoplasm of breast
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   Drug: Trastuzumab emtansine [Kadcyla]
  •   Drug: Lapatinib
  •   Drug: Capecitabine
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Open (masking not used)
  •   [---]*
  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   III
  •   [---]*
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

- 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); PFS was defined as the time from randomization to progressive disease (PD) or death from any cause, whichever occurred earlier. All measurable lesions up to a maximum of 5 per organ and 10 in total, representative of all involved organs, should be identified as target lesions (TL) and recorded and measured at baseline. TLs should be selected on the basis of their size (those with the longest diameter) and their suitability for accurate repeated measurements either by imaging or clinically. A sum of the longest diameter for all TLs will be calculated and reported as the baseline sum longest diameter (SLD). All other lesions (or sites of disease) should be identified as non-TLs and recorded at baseline. PD for TLs was defined as ≥ 20% increase in the SLD, taking as reference the smallest SLD recorded since treatment started or the appearance of 1 or more new lesions. PD for non-TLs was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs.
- 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); Overall survival was defined as the time from the date of randomization to the date of death from any cause. The results reported are from an interim analysis; results from the final analysis will be reported when the study is completed.
- 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); 1 and 2 year survival were defined as the percentage of patients alive 1 and 2 years after starting treatment.

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

Secondary Outcome

- 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); PFS was defined as the time from randomization to progressive disease (PD) or death from any cause, whichever occurred earlier. PD for TLs was defined as ≥ 20% increase in the SLD, taking as reference the smallest SLD recorded since treatment started or the appearance of 1 or more new lesions. PD for non-TLs was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs.
- 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); OR was defined as the percentage of patients with a complete response (CR) or partial response (PR). For TLs, a CR was defined as the disappearance of all TLs and a PR was defined as ≥ 30% decrease in the SLD of TLs, taking as reference the baseline SLD. For non-TLs, a CR was defined as the disappearance of all non-TLs and a PR was defined as the persistence of 1 or more non-TLs.
- 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); Duration of OR was defined as the time from first documented OR to first documented progressive disease (PD) or death from any cause, whichever occurred earlier. PD for target lesions was defined as ≥ 20% increase in the sum of the longest diameter, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of 1 or more new lesions. PD for non-target lesions was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions.
- Clinical Benefit; time frame: 6 months after randomization; Clinical benefit was defined as the percentage of patients with a complete response (CR), partial response (PR), or stable disease (SD) at 6 months after randomization. For target lesions a CR was defined as the disappearance of all target lesions, a PR was defined as ≥ 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. For non-target lesions, a CR was defined as the disappearance of all non-target lesions and a PR was defined as the persistence of 1 or more non-target lesions, and SD was defined as the persistence of 1 or more non-target lesion.
- 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 treatment failure was defined as the time from randomization to discontinuation of treatment for any reason, including progressive disease (PD), treatment toxicity, or death from any cause. PD for target lesions was defined as ≥ 20% increase in the sum of the longest diameter, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of 1 or more new lesions. PD for non-target lesions was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions.
- 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); Time to symptom progression was defined as the time from randomization to the first symptom progression as measured by the Functional Assessment of Cancer Therapy-for patients with Breast Cancer (FACT-B) questionnaire with the Trial Outcomes Index-Physical/Functional/Breast (TOI-PFB) subscale. The FACT-B TOI-PFB subscale contains 24 items from 3 subsections of the FACT-B questionnaire: Physical well-being, functional well-being, and additional concerns for breast cancer patients (breast cancer subscale [BCS]). All items in the questionnaire were rated by the patient on a 5-point scale ranging from 0 ("not at all") to 4 ("very much"). The total score ranged from 0 to 96. A higher score indicates better perceived quality of life. A positive change score from baseline indicates improvement. Symptom progression was defined as a decrease from baseline of 5 points or more.

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   United States
  •   Bosnia and Herzegovina
  •   Brazil
  •   Bulgaria
  •   Canada
  •   Colombia
  •   Denmark
  •   Finland
  •   France
  •   Germany
  •   Hong Kong
  •   India
  •   Italy
  •   Korea, Republic of
  •   Mexico
  •   New Zealand
  •   Philippines
  •   Poland
  •   Portugal
  •   Russian Federation
  •   Singapore
  •   Slovenia
  •   Spain
  •   Sweden
  •   Switzerland
  •   Taiwan, Province of China
  •   United Kingdom
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   [---]*
  •   2009/02/27
  •   980
  •   Multicenter trial
  •   International
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional 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.

end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

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.

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • Genentech
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address scientific-contact
    • Genentech
    • Clinical Trials 
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Genentech
    • Clinical Trials 
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact materialSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting complete, follow-up continuing
  •   [---]*
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

  • [---]*
end of 1:n-Block publications
The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   123
  •   2013/10/30
* This entry means the parameter is not applicable or has not been set.