Bevacizumab, Paclitaxel, Carboplatin, and Radiation Therapy to the Chest in Treating Patients With Locally Advanced Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This phase I trial studies how well giving bevacizumab together with paclitaxel, carboplatin, and radiation therapy to the chest works in treating patients with locally advanced non-small cell lung cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving bevacizumab together with paclitaxel, carboplatin, and radiation therapy may kill more tumor cells.

Detailed Description
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PRIMARY OBJECTIVES: I. Assess the feasibility of administering bevacizumab, paclitaxel, carboplatin, and chest radiotherapy in patients with locally advanced non-small cell lung cancer. II. Characterize the toxicity of this treatment regimen. III. Assess the clinical response to this treatment regimen. IV. Correlate circulating levels of angiopoietin-2 and vascular endothelial growth factor receptor-2 with clinical response to this treatment regimen. OUTLINE: This is an open-label, multicenter study.Induction therapy. Patients receive paclitaxel IV over 1 hour and carboplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, 36, and 43 and bevacizumab IV over 30-90 minutes on days 1, 15, 29, and 43. Patients also undergo chest radiotherapy 5 days a week for 7 weeks beginning on day 1. Consolidation therapy: Beginning 4-5 weeks after completion chemoradiotherapy, patients receive paclitaxel IV over 1 hour followed by carboplatin IV over 1 hour followed by bevacizumab IV over 30 minutes. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. After study completion, patients are followed periodically for 36 months. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Official Title
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A Safety and Feasibility Study of Bevacizumab With Paclitaxel, Carboplatin and Chest Radiotherapy in Patients With Locally Advanced Non-Small Lung Cancer

Conditions
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Adenocarcinoma of the Lung, Bronchoalveolar Cell Lung Cancer, Large Cell Lung Cancer, Stage II Non-small Cell Lung Cancer, Stage IIIA Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer

Intervention / Treatment
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* Radiation: 3-dimensional conformal radiation therapy
* Drug: paclitaxel
* Biological: bevacizumab
* Drug: carboplatin
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed non-small cell lung carcinoma (NSCLC) meeting the following criteria: The following subtypes are eligible: Adenocarcinoma (including bronchoalveolar) Large cell carcinoma (including giant and clear cell carcinomas) Poorly differentiated carcinoma No squamous cell histology Unresectable stage II-III disease Tumor must not invade the trachea or major arterial or venous structures Measurable or evaluable disease Measurable disease defined as ? 1 lesion that can be accurately measured in ? 1 dimension as ? 20 mm with conventional techniques or as ? 10 mm with spiral CT scan No evidence of CNS disease, including primary brain tumor or brain metastases ECOG performance status (PS) 0-1 or Karnofsky PS 60-100% Life expectancy > 6 months Granulocyte count ? 1,500/mm³ Platelet count ? 100,000/mm³ Bilirubin < 1.25 times upper limit of normal (ULN) AST < 2.5 times ULN Creatinine normalOR creatinine clearance ? 60 mL/min FEV_1 ? 1.0 liters 24-hour urine protein < 1,000 mg (for patients with urine protein:creatinine ratio [by urine analysis] > 1.0) No hemoptysis within the past 12 months (defined as bright red blood in sputum of > 1 teaspoon) No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies No history of allergic reactions attributed to carboplatin or taxane No serious or nonhealing wound, ulcer, or bone fracture No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days No significant traumatic injury within the past 14 days No clinically significant cardiovascular disease, including any of the following: Cerebrovascular accident within the past 6 months Uncontrolled hypertension Myocardial infarction or unstable angina within the past 6 months New York Heart Association class II-IV congestive heart failure Serious cardiac arrhythmia requiring medication Unstable angina pectoris Clinically significant peripheral vascular disease No known bleeding diathesis or coagulopathy No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices) No uncontrolled intercurrent illness including, but not limited to, the following: Ongoing or active infection Psychiatric illness or social situations that would limit study compliance Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for ? 6 months after completion of study treatment No HIV positivity No prior chemotherapy No prior epidermal growth factor receptor-targeted therapy No prior vascular endothelial growth factor-targeted therapy No prior chest radiotherapy No major surgery or open biopsy within the past 14 days No concurrent treatment with full-dose anticoagulation Low-dose anticoagulants (e.g., warfarin) to maintain patency of central venous catheter allowed provided all of the following criteria are met: Daily dose of warfarin < 1 mg INR < 1.5 No other concurrent investigational agents No concurrent major surgical procedures No other concurrent anticancer agents or therapies No concurrent chronic treatment with aspirin (> 325 mg daily) or nonsteroidal anti-inflammatory agents No dexamethasone as an antiemetic during chemoradiotherapy No colony-stimulating factors during chemoradiotherapy

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: Treatment (paclitaxel, carboplatin, bevacizumab, radiation)<br>Patients receive paclitaxel IV over 1 hour and carboplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, 36, and 43 and bevacizumab IV over 30-90 minutes on days 1, 15, 29, and 43. Patients also undergo chest radiotherapy 5 days a week for 7 weeks beginning on day 1. Consolidation therapy: Beginning 4-5 weeks after completion chemoradiotherapy, patients receive paclitaxel IV over 1 hour followed by carboplatin IV over 1 hour followed by bevacizumab IV over 30 minutes. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. | Radiation: 3-dimensional conformal radiation therapy<br>* Undergo 3-dimensional conformal radiation therapy<br>* Other names: 3D-CRT;Drug: paclitaxel<br>* Given IV<br>* Other names: Taxol;Biological: bevacizumab<br>* Given IV<br>* Other names: rhuMAb VEGF;Drug: carboplatin<br>* Given IV<br>* Other names: Paraplatin;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and feasibility |  | Up to 36 months | 
| In-field toxicity, defined as bleeding or perforation of the tracheobronchial or gastrointestinal structures within the radiation field |  | Up to 36 months | 
| Clinical response |  | Up to 36 months | 
| Correlation of levels of angiopoietin-2 and vascular endothelial growth factor receptor-2 with clinical response |  | Up to 36 months |