A randomized, open-label, phase III study of taxane based chemotherapy with lapatinib or trastuzumab as a first line therapy for women with HER2/neu positive metastatic breast cancer - COMPLETE
- Conditions
- HER2/neu positive metastatic breast cancerMedDRA version: 9.1Level: LLTClassification code 10027475Term: Metastatic breast cancer
- Registration Number
- EUCTR2007-004568-27-IT
- Lead Sponsor
- GlaxoSmithKline Research and Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 600
1.Histologically confirmed adenocarcinoma of the breast. 2.Metastatic breast cancer (stage IV) at primary diagnosis or at relapse after curative intent therapy. 3.Local or central laboratory confirmed HER2/neu overexpressing and/or amplified disease in the invasive component of the primary or metastatic lesion as defined by: 3+ over expression by IHC (> 30% of invasive tumour cells); 2+ or 3+ (in 30% or less neoplastic cells) overexpression by IHC AND fluorescence or chromogenic in situ hybridization (FISH/CISH) test demonstrating HER2/neu gene amplification;HER2/neu gene amplification by FISH/CISH (> 6 HER2/neu gene copies per nucleus, or a FISH/CISH ratio (HER2 gene copies to chromosome 17 signals) of > 2.2) 4.Formalin fixed, paraffin embedded tumour specimen from the invasive component of the primary or metastatic lesion must be available for central HER2/neu testing to occur either prior to or afterrandomization. The specimens will be used for central laboratory testing of the mandatory tumour phenotype markers ER, PgR, EGFR, CK5/6 and Ki67, once study accrual is completed. 5.Patients must have evidence of metastatic disease, but measurable disease is not mandatory. To be considered evaluable for the overall response rate (complete and partial response), patients must have at least one measurable lesion as follows:X-ray, physical exam > 20 mm, Conventional CT scan, MRI > 20 mm, Spiral CT scan > 10 mm 6.Prior treatment with chemotherapeutic agents including taxanes in the neoadjuvant or adjuvant setting is permitted provided that at least 12 months has elapsed since the last dose of therapy and all treatment related adverse events are < grade 1 at the time of randomization. 7.Prior treatment with HER2/neu targeted therapy in the neoadjuvant or adjuvant setting is permitted provided that at least 12 months has elapsed since last dose of HER2/neu targeted therapy and all treatment related adverse events are < grade 1 at the time of randomization. 8.Prior treatment with endocrine therapy in the neoadjuvant or adjuvant or metastatic setting is permitted provided that therapy has been discontinued and all treatment related adverse events are < grade 1 at the time of randomization. 9.Prior treatments with radiation therapy in the adjuvant and/or metastatic setting are permitted provided that at least 2 weeks have elapsed since the last fraction of radiation therapy and all treatment related adverse events are < grade 1 at the time of randomization. 10. Prior radiation to a solitary metastatic lesion is permitted provided that progression post radiation has been documented. 11.Patients > 18 years of age. 12.life expectancy > 6 months. 13.ECOG performance status 0, 1 or 2 14.Adequate organ and marrow function measured within 14 days prior to randomization as defined below: Hemoglobin > 100 g/L (10 g/dL, 6.206 mmol/L), absolute granulocyte count (AGC) > 1.5 x 109/L (1,500 cells/mm3), Platelet count > 75 x109/L (75,000/mm3), Serum creatinine < 2.0 x institutional upper limit of normal, Total bilirubin < 1.5 x institutional upper limit of normal, ALT(SGPT) +/- AST(SGOT) < 2.5 x institutional upper limit of normal for patients who will be treated with docetaxel therapy ALT (SGPT) +/- AST (SGOT) < 5 x institutional upper limit of normal for patients who will be treated with paclitaxel therapy 15.Left ventricular ejection fraction > 50% as demonstrated by MUGA scan/echocardiogram within 4 weeks prior to randomization. 16.Imaging i
1 Patients with a history of other malignancies, except: adequately treated DCIS, adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours (non-breast) curatively treated with no evidence of disease for > 5 years. 2 Patients who have received prior chemotherapy, immunotherapy, biologic therapy or HER2/neu targeted therapy for recurrent or metastatic breast cancer. 3 Patients receiving ongoing anticancer treatment or other investigational anti-cancer agents for breast cancer or patients who have used an investigational drug within 30 days or 5 half-lives (if known), whichever is longer, preceding the date of randomization. 4 Patients with CNS metastases (including leptomeningeal involvement). 5 Patients with serious cardiac illness or condition including, but not limited to: history of documented congestive heart failure (CHF) or systolic dysfunction (LVEF<50%) high risk uncontrolled arrhythmias (ventricular tachycardia, high-grade AV-block, supraventricular arrhythmias which are not adequately rate-controlled) unstable angina pectoris requiring anti-anginal medication clinically significant valvular heart disease evidence of transmural infarction on ECG inadequately controlled hypertension (systolic blood pressure > 180 mmHg or diastolic blood pressure > 100 mmHg). New York Heart Association (NYHA) Class III or IV functional status (see Appendix X) 6 Pregnant or lactating women. 7 Patients with serious illness or medical condition which would not permit the patient to be managed according to the protocol including, but not limited to: History of significant neurologic or psychiatric disorder which would impair the ability to obtain consent or limit compliance with study requirements. Active uncontrolled infection. Serious or non-healing wound, ulcer, or bone fracture. 8 Patients with peripheral neuropathy grade 2 or greater. 9 Patients with GI tract disease resulting in an inability to take oral medication such as but not limited to malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption (for example resection of stomach or small bowel) or uncontrolled inflammatory GI disease (e.g. Crohn?s, ulcerative colitis). 10 Patients receiving CYP3A4 inhibitors or inducers are not eligible unless it has been > 7 and > 14 days, respectively since the last dose of medication before the start of protocol treatment. For amiodarone in particular, dosing is prohibited for at least 6 months prior to the start of protocol treatment. 11 Patients with history of allergic or hypersensitivity reactions to any study drug or their excipients or with a history of allergic reactions attributed to compounds with similar chemical composition to any of the study drugs. Previous allergic reactions to taxanes that were adequately treated and that, according to the treating physician, would not prohibit further treatment with taxanes, are allowed.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method