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

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.

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