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Clinical Trial Details (PDF Generation Date :- Thu, 14 Jul 2016 07:52:01 GMT) CTRI Number Last Modified On 08/07/2013 Post Graduate Thesis Type of Trial Type of Study Study Design Public Title of Study Scientific Title of Study CTRI/2011/07/001865 [Registered on: 07/07/2011] - Trial Registered Prospectively No Interventional Biological Randomized, Parallel Group, Active Controlled Trial 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) 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 Details of Principal Investigator or overall Trial Coordinator (multi-center study) Details Contact Person (Scientific Query) BO21977 NCT00829166 TDM4370g Protocol Number ClinicalTrials.gov Protocol Number Details of Principal Investigator Roche Products () Pvt. Ltd. The View, 2nd Floor 165, Dr. Mumbai Details Contact Person (Scientific Query) Roche Products () Pvt. Ltd. The View, 2nd Floor 165, Dr. Details Contact Person (Public Query) Details Contact Person (Public Query) Roche Products () Pvt. Ltd. The View, 2nd Floor 165, Dr. page 1 / 5

Source of Monetary or Material Support Primary Sponsor Details of Secondary Sponsor Countries of Recruitment Sites of Study Details of Ethics 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. Type of Sponsor F Hoffmann La Roche Ltd List of Countries Brazil Bulgaria Canada Colombia Denmark Finland France Germany Italy Mexico Poland Portugal Republic of Korea Russian Federation Singapore Slovenia Spain Sweden Switzerland Taiwan United Kingdom United States of America of Principal Investigator Dr B S Ajai Kumar Primary Sponsor Details Genentech Inc 1 DNA Way South San Francisco, CA 94080-4990 U.S.A. Pharmaceutical industry-global Grenzacherstrasse 124 4070 Basel, Switzerland of Site Site Phone/Fax/ 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 ajai.hcg@gmail.com page 2 / 5

Committee of Committee Approval Status Date of Approval Is Independent Ethics Committee? Regulatory Clearance Status from DCGI Health Condition / Problems Studied Intervention / Comparator Agent Inclusion Criteria Central Ethics Committee, HCG Status Approved 02/06/2011 No Date Approved/Obtained 27/06/2011 Health Type Patients Condition Metastatic Breast Cancer Type 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. Age From Age To Gender Details 18.00 Year(s) 99.00 Year(s) Both Inclusion Criteria 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 Details Exclusion Criteria 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 page 3 / 5

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 Method of Concealment Blinding/Masking Stratified randomization Centralized 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 Target Sample Size 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 Total Sample Size=980 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 page 4 / 5

Powered by TCPDF (www.tcpdf.org) REF/2011/06/002450 Phase of Trial Phase 3 Date of First Enrollment () Date of First Enrollment (Global) Estimated Duration of Trial Recruitment Status of Trial (Global) Recruitment Status of Trial () Publication Details Brief Summary Sample Size from =20 05/08/2011 09/02/2009 Years=2 Months=10 Days=0 Closed to Recruitment of Participants Closed to Recruitment of Participants 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. page 5 / 5