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
Official title: 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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Metastatic Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2014-05-21
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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
* 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

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: At time of clinical data cut-off (up to 20 months)
measure: Safety: Percentage of Participants With Adverse Events (AEs)
timeFrame: At time of clinical data cut-off (up to 20 months)
measure: Safety: Percentage of Participants With Grade 3 and 4 AEs
timeFrame: At time of clinical data cut-off (up to 20 months)
measure: Percentage of Participants With Adverse Events Leading to Treatment Discontinuation
timeFrame: At time of clinical data cut-off (up to 20 months)
measure: Safety: Percentage of Participants With Adverse Events Leading to Treatment Interruption
timeFrame: At time of clinical data cut-off (up to 20 months)
measure: Safety: Percentage of Participants With Adverse Events Leading to Dose Reduction
timeFrame: At time of clinical data cut-off (up to 20 months)
measure: Safety: Percentage of Participants With Significant Decline in Left Ventricular Ejection Fraction (LVEF)
timeFrame: At time of clinical data cut-off (up to 20 months)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: At time of clinical data cut-off (up to 20 months)
measure: One-Year Survival Rate
timeFrame: At 12 months
measure: OS Truncated at 2 Years
timeFrame: At 24 months
measure: Objective Response Rate (ORR)
timeFrame: At time of clinical data cut-off (up to 20 months)
measure: Duration of Response (DOR)
timeFrame: At time of clinical data cut-off (up to 20 months)
measure: Pharmacokinetics: Serum Concentrations of Study Medications
timeFrame: 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)
measure: Immunogenicity: Percentage of Positive Anti-Therapeutic Antibody (ATA) Response to Trastuzumab Emtansine
timeFrame: Day 1, Cycle 1 (Day 1), Day 1, Cycle 4 (Day 64) and at study drug completion or discontinuation visit (up to 20 months)
measure: Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire
timeFrame: 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)
measure: Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire
timeFrame: 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)
Other outcomes:
Locations:
city: Daegu
country: Korea, Republic of
city: Gyeonggi-do
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Sabah
country: Malaysia
city: Taipei
country: Taiwan
city: Taipei
country: Taiwan
city: Taoyuan
country: Taiwan
city: Bangkok
country: Thailand
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: