Bevacizumab, Paclitaxel, and Carboplatin Before Surgery in Treating Patients With Stage IB, Stage II, or Stage IIIA Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining monoclonal antibody therapy with chemotherapy before surgery may may shrink the tumor so that it can be removed. PURPOSE: This phase II trial is to see if bevacizumab, paclitaxel, and carboplatin given before surgery work in treating patients who have stage IB, stage II, or stage IIIA non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Determine the clinical complete and partial response rate in patients with stage IB, II, or IIIA resectable non-small cell lung cancer treated with neoadjuvant bevacizumab, paclitaxel, and carboplatin. Determine the pathologic complete response rate in patients treated with this regimen. Determine the ability to proceed with and complete a potentially curative resection in patients treated with this regimen. Determine the safety and toxicity of this regimen in these patients. OUTLINE: Patients receive neoadjuvant bevacizumab IV over 60-90 minutes, paclitaxel IV over 3 hours, and carboplatin IV over 1 hour on day 1. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients undergo surgical resection within 4-6 weeks after completion of chemotherapy. Patients are followed within 3 months. PROJECTED ACCRUAL: A total of 23-39 patients will be accrued for this study.

Official Title
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A Phase 2 Study Of Neoadjuvant rhuMAb VEGF (Bevacizumab) In Combination With Paclitaxel And Carboplatin In Surgically Resectable Non-Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Biological: bevacizumab
* Drug: carboplatin
* Drug: paclitaxel
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed non-small cell lung cancer Stage IB (T2, N0), II (T1 or T2, N1 or T3, N0), or IIIA (T3, N1) Potentially resectable disease No large central primary tumors in proximity to significant blood vessels No bronchoscopically evident endobronchial tumors At least 1 unidimensionally measurable lesion At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan No known brain metastases PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-1 OR Karnofsky 70-100% Life expectancy: More than 12 months Hematopoietic: WBC at least 3,000/mm^3 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 No history of an inherited bleeding disorder No inherited predisposition to a hypercoagulable state No clinically evident hypercoagulable state or bleeding diathesis Hepatic: Bilirubin less than 1.5 times upper limit of normal (ULN) AST/ALT no greater than 2.5 times ULN INR less than 1.5 PTT less than 36 seconds Renal: Creatinine less than 1.5 times ULN OR Creatinine clearance at least 60 mL/min No nephrotic syndrome Urine protein no greater than 0.5 g/24 hours Cardiovascular: No poorly controlled hypertension (greater than 150 mm Hg systolic and/or greater than 100 mm Hg diastolic) despite treatment No uncompensated coronary artery disease No myocardial infarction within the past 6 months No clinically significant or severe peripheral vascular disease No inherited predisposition to thrombosis No deep venous or arterial thrombosis No symptomatic congestive heart failure No unstable angina pectoris within the past 6 months No cardiac arrhythmia No transient ischemic attack within the past 6 months No cerebrovascular accident within the past 6 months No other arterial thromboembolic event within the past 6 months Pulmonary: No hemoptysis No pulmonary embolism Other: No history of allergic reactions to compounds of similar chemical or biologic composition to study drugs No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No psychiatric illness or social situation that would preclude study compliance No significant traumatic injury within the past 28 days No uncontrolled concurrent illness No ongoing or active infection No serious, non-healing wound, ulcer, or bone fracture No other active malignancy No requirement for full-dose anticoagulation or thrombolytic therapy PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy for this cancer No concurrent prophylactic growth factors (e.g., epoetin alfa, filgrastim [G-CSF], or sargramostim [GM-CSF]) Chemotherapy: No prior chemotherapy for this cancer Prior chemotherapy for another malignancy allowed provided the prior malignancy was curatively treated and is currently controlled Endocrine therapy: No prior endocrine therapy for this cancer Radiotherapy: No prior radiotherapy for this cancer Prior radiotherapy for another malignancy allowed provided the prior malignancy was curatively treated and is currently controlled No concurrent radiotherapy Surgery: Prior diagnostic bronchoscopy, mediastinoscopy, or CT-guided biopsy allowed At least 28 days since prior major surgical procedure or open biopsy Other: No other concurrent investigational agents No other concurrent anticancer investigational or commercial agents or therapies No concurrent combination antiretroviral therapy for HIV-positive patients Concurrent low-dose warfarin for maintenence of preexisting, permanent, indwelling IV catheters allowed provided INR less than 1.5

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: Arm A<br>Bevacizumab (15mg/kg, q3wk x 2), Paclitaxel (200 mg/m2, q3wk x 2), carboplatin (AUC of 6, q3wk x 2), followed by surgery 4 to 6 weeks after last dose of Bevacizumab | Biological: bevacizumab<br> <br> Drug: carboplatin<br> <br> Drug: paclitaxel<br> <br> Procedure: conventional surgery<br> <br> Procedure: neoadjuvant therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate (complete and partial responses by RECIST) |  | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I non-small cell lung cancer, stage II non-small cell lung cancer, stage IIIA non-small cell lung cancer