Imatinib Mesylate and Bevacizumab After First-Line Chemotherapy and Bevacizumab in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer

OBJECTIVES:

Primary

• Determine the clinical efficacy of maintenance therapy comprising imatinib mesylate and bevacizumab after completion of first-line, platinum-based chemotherapy and bevacizumab, in terms of progression-free survival, in patients with stage IIIB or IV non-small cell lung cancer.

Secondary

• Assess the safety profile of this regimen in these patients.

OUTLINE: This is an open-label, multicenter study.

Patients receive oral imatinib mesylate twice daily on days 1-21 and bevacizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer

• Stage IIIB (by pleural effusion only) or stage IV disease
• No predominately squamous cell carcinoma

• Mixed tumors will be categorized by predominant cell type
• Must have completed 4 courses of platinum-based, doublet chemotherapy and bevacizumab*, has no disease progression, and meets the following criteria:

• Platinum agent may have included carboplatin or cisplatin
• Second agent may have included paclitaxel, docetaxel, gemcitabine hydrochloride, vinorelbine ditartrate, or pemetrexed disodium
• A change in the platinum doublet is acceptable provided the following are true:

• Basis for change was toxicity rather than disease progression
• Total number of courses of any platinum doublet plus bevacizumab was 4
• At least 3 of 4 courses must have included bevacizumab NOTE: *Patients age 70 and over may have completed 4 courses of single-agent chemotherapy plus bevacizumab; single agent chemotherapy may have included paclitaxel, docetaxel, gemcitabine hydrochloride, vinorelbine ditartrate, or pemetrexed disodium
• No brain metastases by brain MRI or head CT scan

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Bilirubin ≤ 1.25 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• Creatinine ≤ 1.5 times ULN
• Absolute neutrophil count ≥ 1500/mm³
• Platelet count ≥ 100,000/mm³
• INR ≤ 1.5 times ULN
• Urine protein:creatinine ratio ≤ 1
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 3 months after completion of study treatment
• No history of gross hemoptysis (defined as > ½ teaspoon of bright red blood)
• No inadequately controlled hypertension (defined as blood pressure > 150/100 mm Hg on antihypertensive medications)
• No significant traumatic injury within the past 28 days
• No condition requiring continuous administration of systemic corticosteroids
• No medical condition that would preclude study treatment
• No medical comorbidities, including any of the following:

• Unstable angina
• Congestive heart failure ≥ grade 2
• Myocardial infarction within the past 6 months
• Stroke within the past 6 months
• Peripheral vascular disease ≥ grade 2 within the past 6 months

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior systemic chemotherapy in the metastatic setting, except for 4 courses of platinum-based, doublet chemotherapy plus bevacizumab in the first-line setting

• Prior adjuvant, neoadjuvant, or combined modality chemoradiation for localized non-small cell lung cancer allowed provided ≥ 6 months elapsed before metastatic recurrence
• At least 28 days since prior major surgical procedure
• No prior antiangiogenic drug, including AMG 706, CP-547, 632, vatalanib, AZD2171, thalidomide, sorafenib tosylate, or sunitinib malate
• No other concurrent investigational drugs
• No concurrent grapefruit juice or products containing grapefruit
• No other concurrent anticancer agents, including chemotherapy and biological agents
• No concurrent major surgical procedure
• No concurrent therapeutic coagulation comprising warfarin, heparin, or low molecular weight heparin

• Low-dose warfarin (e.g., 1 mg/day) for prophylaxis of central venous catheter thrombosis allowed
• No chronic daily acetylsalicylic acid (> 325 mg/day) or other full-dose nonsteroidal anti-inflammatory drug with antiplatelet activity