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.
Overview
- Phase
- Phase 3
- Intervention
- Trastuzumab Emtansine
- Conditions
- Metastatic Breast Cancer
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 49
- Primary Endpoint
- Progression-Free Survival (PFS)
- Status
- Terminated
- Last Updated
- 9 years ago
Overview
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
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: Trastuzumab Emtansine
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.
Intervention: Trastuzumab
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.
Intervention: Docetaxel
Outcomes
Primary Outcomes
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 Leading to Dose Reduction
Time Frame: 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)
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.
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 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.
Secondary Outcomes
- Duration of Response (DOR)(At time of clinical data cut-off (up to 20 months))
- One-Year Survival Rate(At 12 months)
- Overall Survival (OS)(At time of clinical data cut-off (up to 20 months))
- OS Truncated at 2 Years(At 24 months)
- Pharmacokinetics: Serum Concentrations of Study Medications(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(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(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))
- Objective Response Rate (ORR)(At time of clinical data cut-off (up to 20 months))
- Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire(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))