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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
49

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • Korea, Republic of
      • Daegu, Korea, Republic of, 702-210
      • Gyeonggi-do, Korea, Republic of, 410-769
      • Seoul, Korea, Republic of, 05505
  • Malaysia
      • Sabah, Malaysia, 88996
  • Taiwan
      • Taipei, Taiwan, 100
      • Taipei, Taiwan, 00112
      • Taoyuan, Taiwan, 333
  • Thailand
      • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
Drug: Trastuzumab Emtansine
Trastuzumab emtansine 3.6 milligrams/kilogram (mg/kg) was administered intravenously (IV) over 30-90 minutes Q3W.
Other Names:
  • Kadcyla
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.
Drug: Trastuzumab
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:
  • Herceptin
Drug: Docetaxel
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoffmann-La Roche

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2014

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2016

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 19, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 19, 2014

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 21, 2014

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 7, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 18, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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.

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