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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02144012
Recruitment Status : Terminated
First Posted : May 21, 2014
Results First Posted : March 7, 2017
Last Update Posted : March 7, 2017
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE May 19, 2014
First Posted Date  ICMJE May 21, 2014
Results First Submitted Date  ICMJE January 18, 2017
Results First Posted Date  ICMJE March 7, 2017
Last Update Posted Date March 7, 2017
Study Start Date  ICMJE June 2014
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 18, 2017)
  • 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.
  • 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.
  • 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.
  • Percentage of Participants With Adverse Events Leading to Treatment Discontinuation [ Time Frame: 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) ]
  • Safety: Percentage of Participants With Adverse Events Leading to Dose Reduction [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 19, 2014)
  • Progression-free survival, defined as the time from randomization to the first occurrence of disease progression (with the use of RECIST v1.1) or death from any cause, whichever occurs first, on the basis of investigator assessments [ Time Frame: Up to 66 months ]
  • Safety: Incidence of adverse events (AEs) [ Time Frame: Up to 66 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 18, 2017)
  • 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.
  • One-Year Survival Rate [ Time Frame: At 12 months ]
    One-year survival rate as determined by Kaplan-Meier estimates.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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) ]
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 19, 2014)
  • Overall survival (OS), defined as the time from the date of randomization to the date of death from any cause [ Time Frame: Up to 66 months ]
  • One-year survival rate, Kaplan-Meier estimates [ Time Frame: Up to 66 months ]
  • OS truncated at 2 years, 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 patient's randomization date censored at 2 years [ Time Frame: Up to 66 months ]
  • Objective response rate (ORR), defined as partial response (PR) or complete response (CR) determined on the basis of investigator assessments with the use of RECIST v1.1 [ Time Frame: Up to 66 months ]
  • Duration of response (DOR), defined as the time from the date of initial confirmed PR or CR to the date of disease progression or death within the study [ Time Frame: Up to 66 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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.
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Breast Cancer
Intervention  ICMJE
  • 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 Name: Herceptin
  • Drug: Trastuzumab Emtansine
    Trastuzumab emtansine 3.6 milligrams/kilogram (mg/kg) was administered intravenously (IV) over 30-90 minutes Q3W.
    Other Name: Kadcyla
  • Drug: Docetaxel
    Docetaxel was administered IV at either 75 milligrams/square meter (mg/m^2) or 100 mg/m^2 Q3W.
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Trastuzumab Emtansine
  • 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.
    Interventions:
    • Drug: Trastuzumab
    • Drug: Docetaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: May 29, 2015)
49
Original Estimated Enrollment  ICMJE
 (submitted: May 19, 2014)
561
Actual Study Completion Date  ICMJE January 2016
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Korea, Republic of,   Malaysia,   Taiwan,   Thailand
Removed Location Countries China,   Philippines
 
Administrative Information
NCT Number  ICMJE NCT02144012
Other Study ID Numbers  ICMJE YO28405
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP