Health Condition 1: null- HER2-POSITIVE METASTATIC BREAST CANCER Health Condition 2: C509- Malignant neoplasm of breast of unspecified site
Conditions
Interventions
Intervention1: TRASTUZUMAB EMTANSINE (T-DM1): Patients will be randomized in 2:1 ratio to receive either T-DM1 at a dose of 3.6 mg/kg intravenously on Day 1 of each 21-day cycle or will be receiving T
Sponsors
Genentech Inc
Roche Products India Pvt Ltd
Eligibility
Inclusion criteria
Inclusion criteria: • Signed study-specific Informed Consent Form(s) • Age >= 18 years • Histologically or cytologically documented breast cancer • Metastatic or unresectable locally advanced/recurrent breast cancer • HER2-positive disease documented as ISH-positive and/or 3+ by IHC on previously collected tumor tissue and prospectively confirmed by Sponsor-designated central laboratory prior to study enrolment Tumor blocks or 11 unstained slides available for confirmatory central laboratory HER2 testing and exploratory biomarker analyses Both IHC and ISH assays will be performed; however, only one positive result is required for eligibility. • Disease progression on the last regimen received as defined by the investigator • Prior treatment with an anthracycline, trastuzumab, a taxane, lapatinib, and capecitabine in the neoadjuvant, adjuvant, locally advanced, or recurrent/metastatic setting and documented disease progression (by investigator assessment) after at least two regimens of HER2-directed therapy in the metastatic or unresectable locally advanced/recurrent setting • A minimum of 6 weeks of prior trastuzumab for the treatment of metastatic or unresectable locally advanced/recurrent disease is required. Trastuzumab must have been administered as six consecutive weekly doses or as two consecutive doses on an every-3-week schedule. • Patients must have had at least 6 weeks of prior exposure in the metastatic (or unresectable locally advanced/recurrent) setting to lapatinib and capecitabine (given together or separately) unless they were intolerant of lapatinib and/or capecitabine. Intolerance is defined as any treatment-related Grade 4 adverse event, or any treatment-related Grade 2 or 3 adverse event that is unacceptable to the patient and persists despite standard countermeasures. The reason for intolerance will be fully documented. Patients who were found to be intolerant to lapatinib can be considered eligible if they experienced disease progression during a single trastuzumab-based regimen in the metastatic (or unresectable locally advanced/recurrent) setting. • For patients with hormone-receptorâ??positive disease, disease progression in any setting on prior hormonal therapy • Adequate organ function, as evidenced by the following laboratory results: Absolute neutrophil count > 1500 cells/mm3 Platelet count > 100,000 cells/mm3 Hemoglobin > 9.0 g/dL Patients are allowed to receive transfused red blood cells to achieve this level. Total bilirubin SGOT (AST) and SGPT (ALT) Alkaline phosphatase Patients with hepatic and/or bone metastases: alkaline phosphatase Serum creatinine International normalized ratio (INR) • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (see Appendix B) • LVEF >= 50% by either ECHO or MUGA • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including completion of PRO measures • Negative results of serum p
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria will be excluded from study entry: a. Cancer-Related Criteria • Chemotherapy • Trastuzumab • Lapatinib • Hormone therapy • Investigational therapy or any other therapy • Prior enrollment in a T-DM1â??containing study, regardless of whether the patient received prior T-DM1 • Previous radiotherapy for the treatment of unresectable, locally advanced/recurrent or metastatic breast cancer is not allowed if: The last fraction of radiotherapy has been administered within 14 days prior to randomization. More than 25% of marrow-bearing bone has been irradiated. The patient has not recovered from any resulting acute toxicity (to Grade • Brain metastases that are untreated or symptomatic, or require any radiation, surgery, or steroid therapy to control symptoms from brain metastases within 2 months of randomization • History of intolerance (including Grade 3 or 4 infusion reaction) or hypersensitivity to trastuzumab or murine proteins • History of exposure to the following cumulative doses of anthracyclines: Doxorubicin or liposomal doxorubicin 500 mg/m2 Epirubicin 900 mg/m2 Mitoxantrone 120 mg/m2 If another anthracycline, or more than one anthracycline, has been used, the cumulative dose must not exceed the equivalent of 500 mg/m2 doxorubicin. • Current peripheral neuropathy of Grade >= 3 per the NCI CTCAE, v4.0 • 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 cancers with a similar outcome as those mentioned above b. Cardiopulmonary Function Criteria • Current unstable ventricular arrhythmia requiring treatment • History of symptomatic CHF (New York Heart Association [NYHA] Classes IIâ??IV) • History of myocardial infarction or unstable angina within 6 months of enrollment • History of a decrease in LVEF to 40% or symptomatic CHF with previous trastuzumab treatment • Severe dyspnea at rest due to complications of advanced malignancy or requiring current continuous oxygen therapy c. General Criteria • Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease) • Major surgical procedure or significant traumatic injury within 28 days before enrollment or anticipation of the need for major surgery during the course of study treatment • Current pregnancy or lactation • Current known active infection with HIV, hepatitis B, and/or hepatitis C virus For patients who are known carriers of hepatitis B virus (HBV), active hepatitis B infection must be ruled out based on negative serologic testing and/or determination of HBV DNA viral load per local guidelines. • Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Objective Response Rate (As Determined by the IRF) 2. Overall Survival Timepoint: 1. Objective response is defined as a complete or partial response determined on two consecutive occasions â?¥ 4 weeks apart. 2. Overall survival is defined as the time from the date of randomization to the date of death from any cause. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Objective Response Rate (As Determined by the Investigator) 2. Progression-Free Survival 3. Duration of Objective ResponseTimepoint: 1. assessment will be performed using objective response by investigator assessment. 2. PFS is defined as the time from randomization to documented disease progression or death from any cause, whichever occurs first. 3. duration of objective response is defined as the time from the first tumor assessment that supports the patientâ??s objective response to the time of disease progression or death from any cause, whichever occurs first. | — |
Countries
Australia, Belgium, Brazil, Canada, France, Germany, India, Israel, Italy, Norway, Republic of Korea, Russian Federation, Spain, Sweden, Switzerland, Thailand, United Kingdom, United States of America
Contacts
Public ContactDr Jagdish Nigade
Roche Products (India) Pvt. Ltd
Outcome results
None listed