- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02144012
A Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine Versus the Combination of Trastuzumab Plus Docetaxel in Patients With HER2-positive Breast Cancer
January 18, 2017 updated by: Hoffmann-La Roche
A Randomized, Multicenter, Open-Label Phase III Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine Versus the Combination of Trastuzumab Plus Docetaxel as First-Line Treatment of Patients With Her2-Positive Progressive Or Recurrent Locally Advanced Or Metastatic Breast Cancer.
This is a Phase III, randomized, multicenter, multinational, two-arm, open-label clinical trial to investigate a first-line treatment of participants with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer.
The study will enroll patients with HER2-positive, unresectable, locally advanced breast cancer (BC) if they have recurrent disease or progressive disease (PD) despite primary multi-modality therapy, and/or metastatic BC if they have not received prior chemotherapy for their metastatic disease.
Eligible participants at up to approximately 40 sites in the Asia-Pacific region will be randomized in a 2:1 ratio to receive trastuzumab emtansine (Arm A) or trastuzumab plus docetaxel (Arm B).
All study drugs will be administered at in-clinic visits occurring every three weeks during the treatment phase.
Trastuzumab plus docetaxel was chosen as the comparator in the control group (Arm B), as it represents a common first-line treatment option used in this patient population in China and other Asia-Pacific countries.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
49
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Daegu, Korea, Republic of, 702-210
-
Gyeonggi-do, Korea, Republic of, 410-769
-
Seoul, Korea, Republic of, 05505
-
-
-
-
-
Sabah, Malaysia, 88996
-
-
-
-
-
Taipei, Taiwan, 100
-
Taipei, Taiwan, 00112
-
Taoyuan, Taiwan, 333
-
-
-
-
-
Bangkok, Thailand, 10330
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Age >/= 18 years
- HER2-positive disease, as defined by an immunohistochemistry test score of 3+ and/or in situ hybridization positivity, prospectively confirmed by a Sponsor-designated central laboratory prior to enrollment
- Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease appropriate for chemotherapy
- Patients must have measurable and/or non-measurable disease that is evaluable per the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Adequate organ function
- For women of childbearing potential and men with partners of childbearing potential, agreement by the patient and/or partner to use two adequate non-hormonal forms of contraception during treatment and for at least 6 months after the last dose of study drug
Exclusion Criteria:
- Pregnancy or lactation
- Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; bone fractures, except bone fractures because of disease under study)
- Currently known active infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV)
- Major surgical procedure or significant traumatic injury within approximately 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment
- Current peripheral neuropathy Grade >/= 2 per National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE, v4.0)
- History of systemic anti-cancer therapy after the diagnosis of metastatic breast cancer (MBC) or for recurrent locally advanced disease, with the exception of prior hormonal regimens for recurrent locally advanced disease or MBC
- An interval of < 12 months after the last dose of vinca alkaloid or taxane chemotherapy (i.e., for treatment of early stage, non-metastatic disease)
- Hormonal therapy < 7 days prior to randomization
- Trastuzumab < 21 days prior to randomization
- Lapatinib </= 14 days prior to randomization
- Prior trastuzumab emtansine therapy
- Treatment with any other anti-cancer therapy/investigational drug (not defined above) within 21 days prior to randomization
- History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other malignancies with an expected curative outcome
- Current chronic daily treatment with corticosteroids (dose > 10 mg/day methylprednisone equivalent)
- History of intolerance (including Grade 3 or 4 infusion reaction) or hypersensitivity to trastuzumab, murine proteins, docetaxel or paclitaxel
- Known hypersensitivity any of the study drugs, including excipients, or any drugs formulated in polysorbate 80
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Arm A: Trastuzumab emtansine
Participants will be administered trastuzumab emtansine once every three weeks (Q3W).
Participants may remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first.
|
Trastuzumab emtansine 3.6 milligrams/kilogram (mg/kg) was administered intravenously (IV) over 30-90 minutes Q3W.
Other Names:
|
ACTIVE_COMPARATOR: Arm B: Trastuzumab + Docetaxel
Participants will be administered trastuzumab plus docetaxel Q3W.
Participants may remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first.
|
For the first three-week cycle, trastuzumab was administered IV at 8 mg/kg.
For subsequent cycles, trastuzumab was administered IV at 6 mg/kg Q3W.
Other Names:
Docetaxel was administered IV at either 75 milligrams/square meter (mg/m^2) or 100 mg/m^2 Q3W.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-Free Survival (PFS)
Time Frame: At time of clinical data cut-off (up to 20 months)
|
PFS was defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurred first, on the basis of investigator assessments.
Progression was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 millimeter (mm) or the appearance of one or more new lesions.
|
At time of clinical data cut-off (up to 20 months)
|
Safety: Percentage of Participants With Adverse Events (AEs)
Time Frame: At time of clinical data cut-off (up to 20 months)
|
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment.
An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.
Preexisting conditions which worsen during a study are also considered as adverse events.
|
At time of clinical data cut-off (up to 20 months)
|
Safety: Percentage of Participants With Grade 3 and 4 AEs
Time Frame: At time of clinical data cut-off (up to 20 months)
|
Grade 3 and 4 AEs were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0.
Grade 3 was defined as severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living, including bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden.
Grade 4 was defined as life-threatening consequences; urgent intervention indicated.
|
At time of clinical data cut-off (up to 20 months)
|
Percentage of Participants With Adverse Events Leading to Treatment Discontinuation
Time Frame: At time of clinical data cut-off (up to 20 months)
|
At time of clinical data cut-off (up to 20 months)
|
|
Safety: Percentage of Participants With Adverse Events Leading to Treatment Interruption
Time Frame: At time of clinical data cut-off (up to 20 months)
|
At time of clinical data cut-off (up to 20 months)
|
|
Safety: Percentage of Participants With Adverse Events Leading to Dose Reduction
Time Frame: At time of clinical data cut-off (up to 20 months)
|
At time of clinical data cut-off (up to 20 months)
|
|
Safety: Percentage of Participants With Significant Decline in Left Ventricular Ejection Fraction (LVEF)
Time Frame: At time of clinical data cut-off (up to 20 months)
|
Significant decline in LVEF was defined as LVEF below 50% and decrease from baseline of 15% points or more.
Echocardiogram or multiple-gated acquisition (MUGA) scan was used to assess LVEF.
|
At time of clinical data cut-off (up to 20 months)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival (OS)
Time Frame: At time of clinical data cut-off (up to 20 months)
|
OS was defined as the time from the date of randomization to the date of death from any cause.
|
At time of clinical data cut-off (up to 20 months)
|
One-Year Survival Rate
Time Frame: At 12 months
|
One-year survival rate as determined by Kaplan-Meier estimates.
|
At 12 months
|
OS Truncated at 2 Years
Time Frame: At 24 months
|
OS truncated at 2 years was defined as the time from the date of randomization to the date of death from any cause, with deaths occurring beyond 2 years after the participant's randomization date censored at 2 years.
|
At 24 months
|
Objective Response Rate (ORR)
Time Frame: At time of clinical data cut-off (up to 20 months)
|
ORR was defined as percentage of participants with partial response (PR) or complete response (CR) determined on the basis of investigator assessments with the use of RECIST v1.1.
Tumor assessments were performed with computed tomography (CT) or magnetic resonance imaging (MRI) scans of the chest, abdomen, and pelvis.
CR: disappearance of all target lesions; PR: >=30% decrease in the sum of the longest diameter of target lesions; Objective Response Rate (OR) = CR + PR.
|
At time of clinical data cut-off (up to 20 months)
|
Duration of Response (DOR)
Time Frame: At time of clinical data cut-off (up to 20 months)
|
DOR was defined as the time from the date of initial confirmed PR or CR to the date of disease progression or death within the study.
CR: disappearance of all target lesions; PR: >=30% decrease in the sum of the longest diameter of target lesions.
Disease progression was defined according to RECIST, v1.1 as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions.
|
At time of clinical data cut-off (up to 20 months)
|
Pharmacokinetics: Serum Concentrations of Study Medications
Time Frame: Day 1, Cycle 1 (Day 1), Day 1, Cycle 2 (Day 22), Day 1, Cycle 4 (Day 64) and at study drug completion or discontinuation visit (up to 20 months)
|
Pharmacokinetic (PK) parameters were to be determined in a subset of participants.
PK samples from the first 100 Chinese participants were planned to be collected.
|
Day 1, Cycle 1 (Day 1), Day 1, Cycle 2 (Day 22), Day 1, Cycle 4 (Day 64) and at study drug completion or discontinuation visit (up to 20 months)
|
Immunogenicity: Percentage of Positive Anti-Therapeutic Antibody (ATA) Response to Trastuzumab Emtansine
Time Frame: Day 1, Cycle 1 (Day 1), Day 1, Cycle 4 (Day 64) and at study drug completion or discontinuation visit (up to 20 months)
|
Day 1, Cycle 1 (Day 1), Day 1, Cycle 4 (Day 64) and at study drug completion or discontinuation visit (up to 20 months)
|
|
Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire
Time Frame: On the first Day of each 21-day Cycle (Day 1, 22, 43, etc.) and at study drug completion or discontinuation visit (up to 20 months)
|
The FACT-B (version 4) is a self-reported instrument which measures health-related quality of life (HRQOL) of participants with breast cancer.The FACT-B includes the breast cancer sub-scale (BCS) and is comprised of nine items specific to assessing patients' HRQOL in breast cancer.
|
On the first Day of each 21-day Cycle (Day 1, 22, 43, etc.) and at study drug completion or discontinuation visit (up to 20 months)
|
Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire
Time Frame: Days 1 and 8 of Cycles 1 and 2 and on the first day of each subsequent 21-day cycle thereafter as well as at study drug completion or discontinuation visit (up to 20 months)
|
The FACT - Taxane is a self-reported instrument which measures the HRQOL of participants receiving taxane containing chemotherapy.
The FACT-Taxane consists of 16 items and was designed to assess the impact of taxane treatment-related symptoms from the participant's perspective.
|
Days 1 and 8 of Cycles 1 and 2 and on the first day of each subsequent 21-day cycle thereafter as well as at study drug completion or discontinuation visit (up to 20 months)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
June 1, 2014
Primary Completion (ACTUAL)
January 1, 2016
Study Completion (ACTUAL)
January 1, 2016
Study Registration Dates
First Submitted
May 19, 2014
First Submitted That Met QC Criteria
May 19, 2014
First Posted (ESTIMATE)
May 21, 2014
Study Record Updates
Last Update Posted (ACTUAL)
March 7, 2017
Last Update Submitted That Met QC Criteria
January 18, 2017
Last Verified
January 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Antineoplastic Agents, Immunological
- Docetaxel
- Trastuzumab
- Maytansine
- Ado-Trastuzumab Emtansine
Other Study ID Numbers
- YO28405
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Metastatic Breast Cancer
-
Gilead SciencesRecruitingStudy of Sacituzumab Govitecan (SG) in Japanese Participants With Advanced Solid Tumors (ASCENT-J02)Advanced Solid Tumor | Metastatic Urothelial Cancer | Metastatic Triple-Negative Breast Cancer | HR+/HER2- Metastatic Breast CancerJapan
-
GlycoMimetics IncorporatedTerminatedBreast Cancer | Breast Cancer Metastatic | HR+ Metastatic Breast CancerUnited States
-
BriaCell Therapeutics CorporationRecruitingBreast Cancer | Breast Neoplasm | Metastatic Breast Cancer | Breast Cancer Metastatic | End Stage CancerUnited States
-
OBI Pharma, IncCompletedMetastatic Colorectal Cancer | Metastatic Lung Cancer | Metastatic Breast Cancer | Metastatic Gastric CancerTaiwan
-
Massachusetts General HospitalPuma Biotechnology, Inc.; Celcuity, Inc.WithdrawnMetastatic Breast Cancer | Invasive Breast Cancer | HER2-negative Breast Cancer | ER Positive Breast Cancer | PR-Positive Breast Cancer | Stage IV (Metastatic) Breast CancerUnited States
-
Novartis PharmaceuticalsCompletedMetastatic Breast Cancer | Postmenopausal Women | Locally Advanced Metastatic Breast CancerIsrael
-
Institut de Recherches Internationales ServierADIR, a Servier Group companyCompletedMetastatic Breast Cancer | Metastatic Triple Negative Breast CancerJapan, Belgium, France, Netherlands
-
Prof. Wolfgang JanniEli Lilly and CompanyRecruitingHormone Receptor-positive Metastatic Breast Cancer | HER2-negative Metastatic Breast CancerGermany, Switzerland
-
BriaCell Therapeutics CorporationLumaBridgeEnrolling by invitationBreast Cancer | Breast Neoplasm | Metastatic Breast Cancer | Breast Cancer MetastaticUnited States
-
Gustave Roussy, Cancer Campus, Grand ParisDaiichi SankyoRecruitingAdvanced Breast Cancer | HER2-positive Metastatic Breast Cancer | Breast Cancer Metastatic | HER2 Low Breast CarcinomaFrance
Clinical Trials on Trastuzumab Emtansine
-
National Cancer Institute (NCI)Active, not recruitingHematopoietic and Lymphoid Cell Neoplasm | Advanced Lymphoma | Advanced Malignant Solid Neoplasm | Refractory Lymphoma | Refractory Malignant Solid Neoplasm | Refractory Multiple MyelomaUnited States
-
Academic and Community Cancer Research UnitedNational Cancer Institute (NCI)WithdrawnAnatomic Stage IV Breast Cancer AJCC v8 | Prognostic Stage IV Breast Cancer AJCC v8 | HER2 Positive Breast Carcinoma | Metastatic Breast CarcinomaUnited States
-
Jenny C. Chang, MDGenentech, Inc.; The Methodist Hospital Research InstituteWithdrawnBreast CancerUnited States
-
Hoffmann-La RocheRoche Pharma AGCompletedMetastatic Breast CancerItaly, Spain, Canada, United States, Belgium, France, Germany
-
University of WashingtonNational Cancer Institute (NCI)CompletedStage IV Breast Cancer | Recurrent Breast Carcinoma | Stage IIIB Breast Cancer | Stage IIIC Breast Cancer | HER2/Neu PositiveUnited States
-
Dana-Farber Cancer InstituteMerck Sharp & Dohme LLCActive, not recruiting
-
Hoffmann-La RocheCompletedBreast CancerUnited States, Canada, Spain, France, Italy
-
Genentech, Inc.Completed
-
Spectrum Pharmaceuticals, IncTerminatedBreast CancerUnited States
-
Consorzio OncotechRoche Pharma AGRecruiting