Paclitaxel, Carboplatin Plus Bevacizumab in Pretreated, Advanced or Metastatic 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 paclitaxel, carboplatin and bevacizumab combination, administered biweekly, in patients with pretreated, advanced non small cell lung cancer.

Detailed Description
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The addition of bevacizumab to paclitaxel plus carboplatin in the 1st line treatment of patients with advanced or metastatic non small cell lung cancer (NSCLC) provided a survival benefit. There are patients with NSCLC who have not received bevacizumab and have relapsed after 1st and/or 2nd line therapy. The evaluation of bevacizumab plus chemotherapy in such patients is justified. The combination of paclitaxel and carboplatin, administered every two weeks, has a favorable toxicity profile. This study will evaluate the addition of bevacizumab to a biweekly regimen of paclitaxel and carboplatin as 2nd or 3rd line therapy for NSCLC

Official Title
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Paclitaxel, Carboplatin Plus Bevacizumab in Pretreated, Advanced or Metastatic Non Small Cell Lung Cancer

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Carboplatin
* Drug: Bevacizumab
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed, unresectable locally advanced (stage IIIB) or metastatic (stage IV) non-squamous NSCLC Non-squamous histologic type At least one and no more than two previous chemotherapy regimens for advanced or 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 ≥ 9 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: Previous therapy with paclitaxel in combination with carboplatin Second primary malignancy, except for non-melanoma skin cancer and in situ cervical 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) Symptomatic neuropathy > 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

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>Paclitaxel/Carboplatin/Bevacizumab | Drug: Carboplatin<br>* Carboplatin (IV) 3 AUC on day 1 and day 15 every 4 weeks for 6 cycles<br>Drug: Bevacizumab<br>* Bevacizumab (IV) 10 mg/kg on day 1 and day 15 every 4 weeks for 6 cycles Followed by Bevacizumab (IV) 15 mgr/Kgr on day 1 every 3 weeks until disease progression<br>* Other names: Avastin;Drug: Paclitaxel<br>* Paclitaxel (IV) 140 mg/m2,on day 1 and day 15 every 4 weeks for 6 cycles<br>* Other names: Taxol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall 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 of each chemotherapy cycle | 
| Time to Tumor Progression |  | 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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Non Small Cell Lung Cancer, Paclitaxel, Carboplatin, Bevacizumab