Breast Cancer (HER2-positive and p95HER2-positive metastatic breast cancer) MedDRA version: 14.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female =18 years of age 2. Histologically or cytologically confirmed invasive breast cancer with distant metastasis(ses) (designated as Stage IV or metastatic breast cancer) • Diagnosis with Stage IV or metastatic disease at either primary diagnosis or recurrence 3. Not received prior systemic or local treatment (e.g., chemotherapy, endocrine or radiotherapy) for Stage IV/metastatic breast cancer • Prior adjuvant and/or neo-adjuvant therapy is permitted 4. Documentation of HER2 overexpression or gene amplification, in the invasive component of either a metastatic disease site or primary tumor, defined as: • 3+ by IHC and/or • HER2/neu gene amplification by fluorescence, chromogenic or silver in situ hybridization [FISH, CISH or SISH; >6 HER2/neu gene copies per nucleus or a FISH, CISH or SISH test 5. Documentation by the central laboratory of positive p95HER2 expression in the invasive component of either a metastatic disease site (preferred) or primary tumor 6. No history of CNS metastases (including leptomeningeal involvement) or stable CNS metastases (defined as asymptomatic and off steroids for =3 months) 7. Baseline Left Ventricular Ejection Fraction (LVEF) =50% measured by echocardiography (ECHO) or multi-gated acquisition scan (MUGA) 8. Recovered or stabilized from all adverse events associated with prior anti-cancer therapies, including radiotherapy, at the time of screening 9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 10. Have adequate marrow and organ function as defined in protocol 11. Women of childbearing potential, including women whose last menstrual period was =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: History of other malignancy. Exception: Subjects who have been disease-free for 5 years or subjects with a history of completely resected non-melanoma skin cancer (basal or squamous) are eligible 2. Concurrent anti-cancer treatment or concurrent treatment with an investigational drug 3. Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study treatment 4. Prior treatment with anti-HER2 therapy, except trastuzumab or lapatinib (time from last dose of trastuzumab or lapatinib to randomization must be =3 months) 5. Serious cardiac illness or medical condition including but not confined to: • Uncontrolled arrhythmias • Uncontrolled or symptomatic angina • History of congestive heart failure (CHF) • Documented myocardial infarction <6 months from study entry 6. Current active hepatic or biliary disease (with exception of Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) 7. Concurrent disease or condition, or any pre-existing medical disorder that in the opinion of the investigator may interfere with the subject’s safety, obtaining informed consent or compliance to the study procedures 8. Pregnant or lactating female 9. Any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels (consult with GSK Medical Monitor if uncertain about eligibility) 10. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to any of the study drugs or their excipients (Refer to Section 5.1. of protocol) that, in the opinion of the investigator contra-indicates participation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary endpoint of this study is progression-free survival (PFS) and is defined as the interval between date of randomization and disease progression or death from any cause.;Secondary Objective: Evaluation of: • Overall Survival: defined as the interval between the date of randomization and death from any cause • Overall Response Rate: defined as the percentage of subjects with CR or PR at anytime as per RECIST 1.1 guidelines • Clinical Benefit Response Rate: defined as the percentage of subjects with a CR or PR at any time or SD for = 24 weeks or Non-CR/Non-PD for = 24 weeks as per RECIST 1.1 guidelines Exploratory Endpoints include: • Evaluation of biomarkers known to predict sensitivity or resistance to lapatinib and trastuzumab (i.e., PIK3CA mutations, PTEN aberrations) and determine the relationship with clinical outcome • To identify tumor-derived biomarkers (DNA, RNA and protein) associated with clinical outcome • To evaluate blood-derived biomarkers associated with clinical outcome ;Primary end point(s): The primary endpoint of this study is progression-free survival (PFS) and is defined as the interval between date of randomization and disease progression or death from any cause. | — |
Countries
Ireland, Poland, Spain
Outcome results
None listed