Clinical Trial Details (PDF Generation Date :- Thu, 14 Jul 2016 07:52:01 GMT)
CTRI Number CTRI/2011/07/001865 [Registered on: 07/07/2011] - Trial Registered Prospectively Last Modified On 08/07/2013
Post Graduate Thesis No
Type of Trial Interventional Type of Study Biological
Study Design Randomized, Parallel Group, Active Controlled Trial
Public Title of Study An Open-Label Study of Trastuzumab-MCC-DM1 (T-DM1) vs. Capecitabine + Lapatinib in Patients With HER2-Positive Locally Advanced or Metastatic Breast Cancer (EMILIA)
Scientific Title of Study
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 IDs if Any Secondary ID Identifier
BO21977 Protocol Number
NCT00829166 ClinicalTrials.gov TDM4370g Protocol Number Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Details of Principal Investigator
Name Anil Kukreja
Designation Director-Medical Affairs Affiliation
Address Roche Products (India) Pvt. Ltd. The View, 2nd Floor 165, Dr. Annie Besant Road, Worli, Mumbai
Mumbai MAHARASHTRA 400 018 India Phone 022-24941414 Fax 022-24949500 Email [email protected] Details Contact Person (Scientific Query)
Details Contact Person (Scientific Query)
Name Anil Kukreja
Designation Director-Medical Affairs Affiliation
Address Roche Products (India) Pvt. Ltd. The View, 2nd Floor 165, Dr. Annie Besant Road, Worli, Mumbai
MAHARASHTRA 400 018 India Phone 022-24941414 Fax 022-24949500 Email [email protected] Details Contact Person (Public Query)
Details Contact Person (Public Query)
Name Anil Kukreja
Designation Director-Medical Affairs Affiliation
Address Roche Products (India) Pvt. Ltd. The View, 2nd Floor 165, Dr. Annie Besant Road, Worli, Mumbai
MAHARASHTRA 400 018 India Phone 022-24941414 Fax 022-24949500 Email [email protected] Source of Monetary or Material Support
Source of Monetary or Material Support > F. Hoffmann?La Roche Ltd. Grenzacherstrasse 124 4070 Basel, Switzerland > Genentech, Inc. 1 DNA Way South San Francisco, CA 94080-4990 U.S.A.
Primary Sponsor Primary Sponsor Details
Name Genentech Inc
Address 1 DNA Way South San Francisco, CA 94080-4990 U.S.A. Type of Sponsor Pharmaceutical industry-Global
Details of Secondary Sponsor
Name Address
F Hoffmann La Roche Ltd Grenzacherstrasse 124 4070 Basel, Switzerland Countries of Recruitment List of Countries Brazil Bulgaria Canada Colombia Denmark Finland France Germany India Italy Mexico Poland Portugal Republic of Korea Russian Federation Singapore Slovenia Spain Sweden Switzerland Taiwan United Kingdom
United States of America Sites of Study Name of Principal
Investigator
Name of Site Site Address Phone/Fax/Email Dr B S Ajai Kumar HCG Bangalore
Institute of Oncology
HCG Towers No. 8, P.Kalinga Rao Road Sampangi Rama Nagar Bangalore- 560027 Bangalore KARNATAKA 91-80-40206000 91-80-40206059 [email protected] Details of Ethics page 2 / 5
Committee Name of Committee Approval Status Date of Approval Is Independent Ethics Committee? Central Ethics Committee, HCG Approved 02/06/2011 No Regulatory Clearance Status from DCGI
Status Date
Approved/Obtained 27/06/2011 Health Condition /
Problems Studied
Health Type Condition
Patients Metastatic Breast Cancer
Intervention / Comparator Agent
Type Name Details
Comparator Agent Capecitabine + Lapatinib Lapatinib 1250 mg/day orally once per day of a 21-day cycle + capecitabine 1000 mg/m2 orally twice daily on Days 1?14 of a 21-day cycle Duration : Progressive Disease or until death, whichever occurs first. Intervention Trastuzumab-MCC-DM1 T-DM1 3.6 mg/kg intravenously
(IV) over 30?90 minutes on Day 1 of a 21-day cycle Duration : Progressive Disease or until death, whichever occurs first.
Inclusion Criteria Inclusion Criteria
Age From 18.00 Year(s)
Age To 99.00 Year(s)
Gender Both
Details There is no upper age limit in the trial
1. HER2 status must be prospectively, centrally tested and be HER2-positive based on central laboratory assay results
2. Histologically or cytologically confirmed invasive breast cancer 3. 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
4. Documented progression of incurable, unresectable, locally advanced or metastatic breast cancer, defined by the investigator 5. Measurable and/or nonmeasurable disease; patients with central nervous system (CNS)-only disease are excluded
6. Cardiac ejection fraction 0% by either ECHO or MUGA
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
8. 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 Exclusion Criteria
Details 1. History of treatment with T-DM1
2. Prior treatment with lapatinib or capecitabine
3. Peripheral neuropathy of Grade 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 curative outcome as those mentioned above
5. History of receiving any anti-cancer drug/biologic or investigational treatment within 21 days prior to randomization except hormone therapy, which can be given up to 7 days prior to randomization; recovery of treatment-related toxicity consistent with other eligibility criteria
6. History of radiation therapy within 14 days of randomization 7. 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 8. History of symptomatic congestive heart failure (CHF) or serious cardiac arrhythmia requiring treatment
9. History of myocardial infarction or unstable angina within 6 months of randomization
10. Current dyspnea at rest due to complications of advanced malignancy or current requirement for continuous oxygen therapy 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
Method of Generating Random Sequence Stratified randomization Method of Concealment Centralized Blinding/Masking Open Label
Primary Outcome Outcome Timepoints
1. Incidence, nature, and severity of adverse events
2. Overall survival and landmark survival rate 3. Progression-free survival (PFS) by Independent Review Committee assessment
1. Through study completion or early study discontinuation
2. Time from randomization to death 3. Time from randomization to the first occurrence of progression or death
The expected end of the study is Nov-2013.
Secondary Outcome Outcome Timepoints
1. To compare the overall ORR between the two treatment arms on the basis of both investigator and independent review of tumor assessments 2. To estimate the duration of objective response within each treatment arm on the basis of both investigator and independent review of tumor assessments
3. To compare PFS between the two treatment arms on the basis of investigator review of tumor assessments
1. Confirmed response at least 28 days after initial documentation of response
2. First occurrence of a documented objective response until the time of disease progression 3. Time from randomization to the first occurrence of progression or death
Target Sample Size Total Sample Size=980
Sample Size from India=20 Phase of Trial Phase 3
Date of First Enrollment (India) 05/08/2011 Date of First Enrollment (Global) 09/02/2009 Estimated Duration of Trial Years=2 Months=10 Days=0 Recruitment Status of Trial (Global)
Closed to Recruitment of Participants Recruitment Status of
Trial (India)
Closed to Recruitment of Participants Publication Details
Brief Summary This is a Phase III, randomized, multicenter, international, two-arm, open-label clinical trial designed to compare the safety and efficacy of T-DM1 with that of capecitabine + lapatinib for HER2-positive MBC. A total of 980 patients will be enrolled at more than 200 sites worldwide. Eligible patients will be randomized in a 1:1 ratio to either T-DM1 or lapatinib + capecitabine.
