Vinorelbine Metronomic Plus Lapatinib for Overexpressing HER-2 Metastatic Breast Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of metronomic oral vinorelbine taken three times a week plus daily lapatinib without break, as salvage treatment in patients with metastatic breast cancer.

Detailed Description
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Continuous administration of oral vinorelbine, given three times a week (metronomic) is feasible and exceptionally well tolerated at doses up to 50 mg. Early results show activity against refractory tumors and provide evidence towards clinical proof of efficacy for metronomic chemotherapy. Recently, lapatinib plus capecitabine was proven superior to capecitabine alone in women with HER2-positive advanced breast cancer that has progressed after treatment with regimens that included an anthracycline, a taxane, and trastuzumab.

Official Title
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Vinorelbine Metronomic Plus Lapatinib as Salvage Therapy for Patients With Overexpressing HER-2 Metastatic Breast Cancer. A Multicenter Phase II Study

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Vinorelbine
* Drug: Lapatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically- or cytologically- confirmed metastatic breast adenocarcinoma Age 18-75 years HER2 status positive according to the local institution reported grade 3+ staining intensity (on a scale of 0 to 3) by means of immunohistochemical analysis or grade 2+ staining intensity by means of immunohistochemical analysis with gene amplification on fluorescence in situ hybridization Previous therapies had to include, regimens containing an anthracycline and a taxane Previous treatment with trastuzumab, alone or in combination with chemotherapy for locally advanced or metastatic disease, is required Measurable disease as defined by the presence of at least one measurable lesion (except bone metastases, ascites or pleural effusions) Performance status (WHO) 0-2 Adequate liver (serum bilirubin <1.5 times the upper normal limit; AST and ALT <2.5 times the upper normal limit in the absence of demonstrable liver metastases, or <5 times the upper normal limit in the presence of liver metastases); adequate renal function (serum creatinine <1.5 times the upper normal limit); and bone marrow (neutrophils ≥ 1.5x 109 /L, and platelets ≥ 100x 109 /L) function No radiation of measurable disease (except brain metastases) No progressive brain metastases according to clinical or radiological criteria No brain metastases without prior radiation therapy Written informed consent Exclusion Criteria: Patient unable to take oral medication Active infection History of significant cardiac disease (unstable angina, congestive heart failure, myocardial infarction within the previous 6 months, ventricular arrhythmias) Other invasive malignancy except nonmelanoma skin cancer Psychiatric illness or social situation that would preclude study compliance Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Vinorelbine metronomic/Lapatinib | Drug: Vinorelbine<br>* Vinorelbine p.o (50 mg 3 times a week) until disease progression or appearance of unacceptable toxicity<br>* Other names: Navelbine;Drug: Lapatinib<br>* Lapatinib p.o every day without interruption disease progression or appearance of unacceptable toxicity<br>* Other names: Tykerb;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate |  | 3 - 6 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival |  | 1 year | 
| Toxicity profile |  | 21 days | 
| Overall Survival |  | 1 year | 
| Quality of life assessment |  | 42 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vinorelbine metronomic-lapatinib, Chemotherapy, Targeted therapy