Dose Finding Study for Combination of Capecitabine, Lapatinib and Vinorelbine in Metastatic Breast Cancer

Study Overview
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Brief Summary
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The purpose of the study is to investigate safety and efficiency of the triple combination of capecitabine, lapatinib and vinorelbine in patients with metastatic breast cancer.

Detailed Description
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The combination of lapatinib with capecitabine ist a standard therapy für Her2 positive metastatic breast cancer. This study combines this therapy with the additional antimitotic mode of function by vinorelbine.

Official Title
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Combinational Therapy of Capecitabine, Lapatinib and Vinorelbine for the Treatment of Patients With her2/Neu Positive, Relapsed or Metastatic Breast Carcinoma Following Treatment Failure With Trastuzumab

Conditions
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Metastatic Breast Cancer, HER2 Positive, First or Second Line Therapy, Failure or Contraindication of Trastuzumab Therapy

Intervention / Treatment
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* Drug: Lapatinib and Capecitabine and Vinorelbine


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Written informed consent Able to comply with the protocol ECOG performance status 0-1 Adequate contraception Confirmed Her2/neu-positive, adenocarcinoma of the breast At least one measurable lesion according to RECIST 1.1 criteria First or second chemotherapy after diagnosis of metastasis Lapatinib treatment indicated (adjuvant trastuzumab treatment <12 months ago or progressive disease with trastuzumab treatment) No signs and symptoms of CHF (chronic heart failure), LVEF (left ventricular ejection fraction) at study start at least 55% Adequate hepatic and renal function value Adequate hematologic function values Exclusion Criteria: Pregnant or lactating women Concurrent participation in another clinical trial. Prior participation is allowed if the last study medication was administered more than 4 weeks prior to randomization Asymptomatic with regards to tumor illness Previous treatment with lapatinib, capecitabine or vinorelbine Necessity of planned treatment with other chemotherapeutics oder anti-hormone therapy Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during the course of the study Evidence of cardiovascular disease, e.g. myocardial infection, unstable angina pectoris or arrhythmia History of vascular or cardiovascular disease within the past 6 months All illnesses that result in malabsorption of oral medication or inability to take oral medication Concurrent treatment with anti-viral drugs based on sorivudine or with aminoglycosides Concurrent treatment with any drug interfering with study medication, especially, those that induce CYP3A Concurrent treatment with allopurinol Other malignancies (except for basal cell carcinoma of the skin and cervical carcinoma in situ); patient can be included in the study if no recurrent disease has been observed for at least 5 years Concurrent illnesses or other circumstances that could interfere with trial participation, efficacy or safety of the patient

Ages Eligible for Study
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Minimum Age: 18 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: Capecitabine, Lapatinib, Vinorelbine<br> | Drug: Lapatinib and Capecitabine and Vinorelbine<br>* Dose finding Study Lapatinib: 1000-1250 oral, once daily, days 1-21 Capecitabine: 1000 mg/sqm oral, bid, days 1-14 Vinorelbine 10-22,5 mg/sqm, i.v. Day 1 + 8<br>* Other names: Navirel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of maximal tolerable Dose (MTD) of combination with Capecitabine and Lapatinib and Vinorelbine | Phase I: Identification of Dosis limiting toxicities and maximal tolerable dose for Combinational therapy (Time Frame: within the first 21 days under medication) | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response Rate | Measurement with CT or MRI after three and six cycles and every three months, as long no tumor progression is detected. | 12 months | 
| Progression free survival | Measurement with CT or MRI after three and six cycles and every three months, as long no tumor progression is detected. | 12 months | 
| Time to treatment failure (TTF) | Measurement with CT or MRI after three and six cycles and every three months, as long no tumor progression is detected. | 12 months | 
| Overall survival (OS) | Measurement with CT or MRI after three and six cycles and every three months, as long no tumor progression is detected. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dose finding study, Combination