None listed
Conditions
Interventions
Group 1 Type of group
Lapatinib (1250mg once daily) in combination with chemotherapy (docetaxel, paclitaxel or vinorelbine) selected at the discretion of the investigator
Group name:Group 2 Type of group
Trastuzumab (either 6mg/kg q3-weekly or 2mg/kg weekly) in combination with chemotherapy (docetaxel, paclitaxel or vinorelbine) selected at the discretion of the investigator
Sponsors
GlaxoSmithKline,
Eligibility
Sex/Gender
Female
Age
18 Years to 120 Years
Inclusion criteria
Inclusion criteria: • Female ≥ 18 years of age • 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 • 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 • 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 ratio (HER2 gene copies to chromosome 17 signals) of ≥2.0] • Documentation by the central laboratory of positive p95HER2 expression in the invasive component of either a metastatic disease site (preferred) or primary tumor • No history of CNS metastases (including leptomeningeal involvement) or stable CNS metastases (defined as asymptomatic and off steroids for ≥ 3 months) • Baseline Left Ventricular Ejection Fraction (LVEF) ≥50% measured by echocardiography (ECHO) or multi-gated acquisition scan (MUGA) • Recovered or stabilized from all adverse events associated with prior anti-cancer therapies, including radiotherapy, at the time of screening • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 • Have adequate marrow and organ function as defined as: • SYSTEM LABORATORY VALUES Hematologic ANC ≥1.5 x 109/L Hemoglobin ≥9 g/dL (after transfusion if needed) Platelets ≥100 x 109/L Hepatic Albumin ≥ 2.5 g/dL Serum bilirubin ≤1.5 x ULN unless due to Gilbert´s syndrome AST and ALT ≤3 x ULN Renal Calculated creatinine clearance ≥ 40 mL/min Serum Creatinine ≤1.5 mg/dL or 132.6µmol/L (Abbreviations: ANC, absolute neutrophil count; ULN, upper limit of normal; AST, aspartate aminotransferase; ALT, alanine aminotransferase) • Women of childbearing potential, including women whose last menstrual period was <12 months ago (unless surgically sterile) must have a negative serum pregnancy test and agree to use effective contraception, as defined in protocol • Signed Informed Consent Form
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 • Concurrent anti-cancer treatment or concurrent treatment with an investigational drug • Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study treatment • Prior treatment with anti-HER2 therapy, except trastuzumab or lapatinib (time from last dose of trastuzumab or lapatinib to randomization must be ≥3 months) • 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 • Current active hepatic or biliary disease (with exception of Gilbert´s syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) • 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 • Pregnant or lactating female • 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) • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to any of the study drugs or their excipients that, in the opinion of the investigator contra-indicates participation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:It will be evaluated in the ITT population and is defined as the interval between the date of the random distribution and the date of the objective progression of the disease or death from any cause. The progression of the disease will be based on the evaluation from the investigators review of the objective evidence of progression (e.g., radiological images and medical photographs). Measure:Progression-free survival Timepoints:Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:Defined as the interval between the date of random distribution and the date of death from any cause. In the case of subjects who do not die, the moment of death will be censored on the date of the last contact. The OS will be summarized using the Kaplan-Meier curves from which the median time to death will be calculated, along with quartiles of 25 and 75% and CI of approximately 95%. The treatment branches will be compared with the use of a stratified logarithmic range test, with stratification for the concomitant chemotherapeutic agent (taxane versus vinorelbine) and previous anti-HER2 therapy (yes vs. no). Measure:Overall Survival Timepoints:12 weeks ; Outcome name:Defined as the percentage of subjects that reach either a CR or a PR. The ORR will be calculated from the investigators evaluation of the best response. Subjects with measurable disease in the baseline period will be included in the ORR analysis. Subjects with unknown or absent response will be considered as unanswered subjects, that is, they will be included in the denominator when calculating the percentage. The exact 95% CI for the tumor response rates in each branch will be calculated. The treatment branches will be compared with the use of Fishers exact tests. Measure:global response rate Timepoints:12 weeks ; Outcome name:Defined as the percentage of subjects who experience a tumor response either complete or partial at any time or who maintain a stable disease for at least 24 weeks. Subjects with unknown or absent response will be considered as unanswered subjects, that is, they will be included in the denominator when calculating the percentage. The exact 95% CI for the tumor response rates in each branch will be calculated. The treatment branches will be compared with the use of Fishers exact tests. Measure:clinical benefit response rate Timepoints:12 weeks | — |
Countries
Ireland, Peru, Poland, Spain
Contacts
Public ContactSarita Mattos
GLAXOSMITHKLINE PERU S.A.
Outcome results
None listed