Metronomic Vinorelbine and Bevacizumab in Patients With Non Small Cell Lung Cancer

Study Overview
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Brief Summary
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This trial will evaluate the efficacy and safety of metronomic vinorelbine and bevacizumab combination in patients with pretreated, advanced non small cell lung cancer

Detailed Description
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Intravenous (IV) vinorelbine is a standard chemotherapy option for the treatment of metastatic NSCLC, either alone or in combination with other agents such as CDDP or Carboplatin with overall response rates (ORR) of 15-35% as 1st line treatment and less than 10% as salvage treatment. For the past few years vinorelbine is available for per os (po) administration with acceptable and reliable pharmacokinetic profiles and with a bioavailability of approximately 40% of the IV dose. In randomized phase II studies IV and po vinorelbine have shown comparable response and overall survival rates. The low dose metronomic chemotherapy that is administered in short intervals has been shown in vitro an in vivo to have antiangiogenic effects. Bevacizumab is a well known anti-angiogenic agent. Recently, a phase III study of 1st line treatment in patients with advanced or metastatic NSCLC showed that the addition of bevacizumab to a platinum-based regimen provided a survival benefit. This study will evaluate the combination of metronomic vinorelbine and bevavizumab as 2nd line treatment of NSCLC.

Official Title
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A Phase II Study of the Combination of Metronomic Vinorelbine and Bevacizumab as 2nd Line Treatment in Patients With Non Small Cell Lung Cancer (NSCLC)

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Vinorelbine
* Drug: Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed, metastatic (stage IV) non small cell lung cancer One previous platinum based chemotherapy regimen with or without taxanes for metastatic NSCLC Measurable disease, defined as at least 1 bidimensionally measurable lesion ≥ 20 X 10 mm Age ≥ 18 years Performance status (WHO) 0-2 Life expectancy of at least 12 weeks Adequate bone marrow (ANC ≥ 1,500/mm3, PLT ≥ 100,000/mm3, Hgb ≥ 11 g/dL), liver (Bilirubin ≤ 1.5 upper normal limit, SGOT/SGPT ≤ 2.5 upper normal limit in the absence of liver metastases or ≤ 5 upper normal limit in the presence of liver metastases), and renal function (Creatinine ≤ 1,5 upper normal limit) Patients must be able to understand the nature of this study Written informed consent Exclusion Criteria: Second primary malignancy, except for non-melanoma skin cancer. Pregnant or lactating women Any serious, uncontrolled comorbidity on the investigator's judgment Uncontrolled infection Any sustained chronic toxicity > grade 2 according to the NCI CTCAE (version 3.0) Brain metastases, except if radiated and asymptomatic Radiotherapy within the previous 4 weeks Previous radiotherapy to the only measurable lesion Proteinuria ≥ 500 mgr of protein daily Hemoptysis > 10 cc per event Clinically significant hematemesis Centrally located lesion or in contact with major vessels Pulmonary lesion with cavitation Documented hemorrhagic diathesis or coagulation disorder Cardiovascular disease (class II-IV NYHA congestive heart failure, myocardial infarction within the previous 4 months, unstable angina, LVEF < normal, ventricular arrhythmia, uncontrolled hypertension) Thrombotic event within the previous 6 months Concurrent use of aspirin > 325 mgr daily, low molecular weight heparin in therapeutic dose, warfarin or acenocoumarol, non-steroid anti-inflammatory agents Concurrent treatment with other anti-cancer drug Major surgical procedure within the previous 4 weeks Serum Να+ < 120mg/dL

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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 + bevacizumab | Drug: Vinorelbine<br>* Metronomic vinorelbine (p.o) 30 mg total dose/day, every Monday, Wednesday and Friday of each week, continuously without intervals for the equivalence of 6 cycles maximum<br>* Other names: Navelbine;Drug: Bevacizumab<br>* Bevacizumab (IV) 10 mgr/Kgr on day 1 and 15 every 4 weeks for 6 cycles maximum followed by Bevacizumab (IV) 10 mgr/Kgr on day 1 and 15 every 4 weeks until disease progression<br>* Other names: Avastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate |  | Objective responses confirmed by CT or MRI (on 3rd and 6th cycle) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity profile |  | Toxicity assessment on each cycle | 
| Progression free survival |  | 1 year | 
| Overall survival |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vinorelbine, Bevacizumab, Chemotherapy