Radiation Therapy, Chemotherapy, and Bevacizumab in Treating Patients With Recurrent, Unresectable or Stage III or Stage IV Non-Small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. 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. 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. Giving radiation therapy together with chemotherapy and monoclonal antibody therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving radiation therapy together with chemotherapy and bevacizumab works in treating patients with recurrent, unresectable or stage III or stage IV non-small cell lung cancer.

Detailed Description
-----------------
OBJECTIVES: Primary Evaluate reduction in toxicity, in terms of pulmonary hemorrhage, in patients with recurrent, unresectable or stage IIIB or IV squamous non-small cell lung cancer treated with radiotherapy followed by paclitaxel, carboplatin, and bevacizumab. Secondary Determine the overall and progression-free survival of patients treated with this regimen. OUTLINE: Patients undergo radiotherapy to the primary tumor, clinically involved lymph nodes, and any other disease-causing symptoms or bronchial compression once daily, 5 days a week, for 2 weeks in weeks 1 and 2. Beginning in week 4, patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment with paclitaxel, carboplatin, and bevacizumab repeats every 3 weeks for 4 courses in the absence of unacceptable toxicity. Patients achieving complete response, partial response, or stable disease after 4 courses receive bevacizumab alone as above in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 6 months. PROJECTED ACCRUAL: A total of 32 patients will be accrued for this study.

Official Title
-----------------
Phase II Study of Radiation Followed by Paclitaxel, Carboplatin, and Bevacizumab (PCA) in Patients With Stage IIIB and IV Squamous Non-Small Cell Lung Cancer

Conditions
-----------------
Lung Cancer

Intervention / Treatment
-----------------
* Biological: bevacizumab
* Drug: carboplatin
* Drug: chemoprotection
* Drug: paclitaxel
* Radiation: radiation therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) Predominantly squamous cell histology Cytologic or histologic elements can be established on metastatic tumor aspirates or biopsy Advanced disease, meeting 1 of the following staging criteria: Stage IIIB disease with malignant pleural effusion Stage IV disease Recurrent, unresectable disease Measurable or nonmeasurable disease No extrathoracic only disease No known CNS metastases by head CT scan with contrast or MRI PATIENT CHARACTERISTICS: ECOG performance status 0-1 Platelet count > 100,000/mm^3 Absolute neutrophil count > 1,500/mm^3 Bilirubin < 1.5 mg/dL Transaminases < 5 times upper limit of normal (ULN) Creatinine clearance ≥ 45 mL/min Urine protein:creatinine ratio ≤ 1.0 by spot urinalysis INR < 1.5 ULN PTT normal Not pregnant or nursing Negative pregnancy test Fertile patients use effective contraception No serious nonhealing wound, ulcer, or bone fracture No ongoing or active infection No ongoing fever No myocardial infarction within the past 6 months No stroke within the past 6 months No history of hypertension unless well-controlled (i.e., blood pressure < 150/100 mmHg on a stable regimen of antihypertensive therapy) No New York Heart Association grade III or IV congestive heart failure No serious cardiac arrhythmia requiring medication No unstable angina pectoris No peripheral vascular disease ≥ grade 2 No other clinically significant cardiovascular disease No abdominal fistula No gastrointestinal perforation No intra-abdominal abscess within the past 6 months No psychiatric illness or social situation that would preclude study compliance No other malignancy curatively treated within the past 5 years No history of thrombotic or hemorrhagic disorders No gross hemoptysis (i.e., red blood ≥ ½ teaspoon) within the past 3 months No bleeding requiring intervention or ≥ grade 2 PRIOR CONCURRENT THERAPY: Recovered from prior therapy No prior systemic chemotherapy for metastatic NSCLC More than 6 months since prior adjuvant chemotherapy for early stage (i.e., stage IB-IIIA) NSCLC More than 3 weeks since prior immunotherapy, hormonal therapy, or radiotherapy More than 28 days since prior and no concurrent major surgery More than 7 days since prior minor surgery, fine-needle aspiration, or core biopsy More than 4 weeks since prior and no concurrent participation in another experimental drug study No concurrent therapeutic anticoagulation Concurrent prophylactic anticoagulation of venous access device allowed No concurrent chronic treatment with aspirin (> 325 mg/day) or nonsteroidal anti-inflammatory drugs known to inhibit platelet function No concurrent dipyridamole, ticlopidine, clopidogrel, or cilostazol

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: bevacizumab|nan|
|Drug: carboplatin|nan|
|Drug: chemoprotection|nan|
|Drug: paclitaxel|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in toxicity measured by pulmonary hemorrhage rate |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival by Kaplan-Meier |  |  | 
| Response rate |  |  | 
| Toxicity |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
recurrent non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, squamous cell lung cancer