A study to determine the comparative efficacy of Lapatinib vs. Trastuzumab, Each with a Taxane, in the treatment of First Line Metastatic Breast Cancer
- Conditions
- Health Condition 1: null- Women with documented evidence of HER2/neu positive metastatic breast cancer
- Registration Number
- CTRI/2011/08/001962
- Lead Sponsor
- GlaxoSmithKline Pharmaceuticals Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 650
Eligibility Criteria Subjects eligible for enrolment in the study must meet all of the following criteria:
Histologically confirmed adenocarcinoma of the breast designated as Stage IV metastatic breast cancer at primary diagnosis or at relapse after curative intent therapy.
Local or central laboratory confirmed HER2/neu over-expression 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)
Formalin fixed, paraffin embedded tumour tissue block from the invasive component of the primary or metastatic lesion must be available for central HER2/neu testing to occur either prior to (if no local HER2/neu testing available or if the result of the local HER2/neu testing is equivocal) or after randomization. In addition, the tumour tissue block 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. This requires the submission of a paraffin block containing sufficient primary tumour tissue for HER2/neu analysis and the mandatory tumour phenotype markers to the central laboratory (Centre for Translational and Applied Genomics (CTAG) at the British Columbia Cancer Agency (BCCA), Vancouver, BC, Canada). Where required by the enrolling institution, tissue blocks will be returned after sampling. Failure to provide blocks for central HER2/neu testing will exclude patients from randomization. Where local centre regulations prohibit submission of blocks of tumour tissue, or where slides are the only available source of tissue, the approval of the NCIC CTG must be sought on whether such patients may be admissible for randomization to the study.
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
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.
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.
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.
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
Ineligibility Criteria Subjects who fulfill any of the following criteria are not eligible for admission to the study:
Patients with a history of other malignancies, except: adequately treated DCIS or LCIS, 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.
Patients who have received prior chemotherapy, immunotherapy, biologic therapy or HER2/neu targeted therapy for recurrent or metastatic breast cancer.
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.
Patients with CNS metastases (including leptomeningeal involvement).
Patients with serious cardiac illness or condition including, but not limited to:
? history of documented congestive heart failure (CHF)
? systolic dysfunction (LVEF50%)
? 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)
Pregnant or lactating women.
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.
Patients with peripheral neuropathy grade 2 or greater.
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).
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 (see Appendix IX). For amiodarone in particular, dosing is prohibited for at least 6 months prior to the start of protocol treatment.
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
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Progression Free SurvivalTimepoint: At the end of 24 weeks or until disease progression
- Secondary Outcome Measures
Name Time Method Clinical Benefit Response Rate (CR or PR, or Stable disease at end of week 24)Timepoint: At end of 24 weeks or until disease progression.;Overall response rateTimepoint: At end of 24 weeks or until disease progression.;Overall SurvivalTimepoint: At end of 24 weeks or until disease progression.;Time to CNS Metastasis at the time of first progression.Timepoint: At end of 24 weeks or until disease progression.;Time to response and duration of response.Timepoint: At end of 24 weeks or until disease progression.