S0636: Erlotinib and Bevacizumab in Never-Smokers With Stage IIIB or Stage IV Primary Non-Small Cell Lung Cancer

OBJECTIVES:

Primary

• Assess overall survival of patients with stage IIIB or IV primary non-small cell lung adenocarcinoma who have never smoked and are treated with erlotinib hydrochloride and bevacizumab.

Secondary

• Assess progression-free survival of patients treated with this regimen.
• Assess the response rate (confirmed and unconfirmed, complete and partial) in a subset of patients with measurable disease treated with this regimen.
• Evaluate the frequency and severity of toxicities associated with this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral erlotinib hydrochloride daily on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 3 years.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

• Adenocarcinoma

• No component of squamous cell carcinoma present
• Incompletely resected or unresectable disease
• Stage IIIB or IV disease as defined below:

• Selected stage IIIB disease

• T4 (cytologically confirmed malignant pleural effusion OR pleural tumor foci that are separate from direct pleural invasion by the primary tumor)
• Any N
• M0
• Stage IV disease

• Any T
• Any N
• M1 (distant metastases present)
• Recurrent lung cancer in a separate lobe after resection or radiotherapy within the past 5 years OR multifocal lesions in > 1 lobe considered stage IV disease
• New lesions occurring ≥ 5 years after resection may be considered a separate primary cancer and are not allowed if this is the only focus of lung cancer
• Measurable and/or nonmeasurable disease by CT scan, positron emission tomography scan, or MRI

• Disease must be present outside a previous radiotherapy field OR a new lesion must be inside the port
• Measurable disease must be assessed within the past 28 days
• Nonmeasurable disease must be assessed within the past 42 days
• Pleural effusions, ascites, and laboratory parameters are not acceptable as the only evidence of disease
• Must be a lifelong nonsmoker (< 100 cigarettes in lifetime)
• Treated brain metastases allowed provided the patient is asymptomatic and do not require steroids

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-2
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Total bilirubin normal
• SGOT or SGPT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases present)
• Alkaline phosphatase ≤ 2.5 times ULN (5 times ULN if bone metastases present)
• Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 50 mL/min
• Urine protein:creatinine ratio ≤ 0.5 OR urine protein < 1,000 mg by 24-hour urine collection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Hypertension allowed if controlled on medication prior to study enrollment
• Must be willing to provide prior smoking history
• No immediate life-threatening complications from malignancies
• No prior major medical condition, psychological condition, or social situation that would preclude study treatment
• No hemoptysis ≥ ½ teaspoon within the past 28 days
• No clinical history of pulmonary or upper respiratory hemorrhage ≥ grade 2 within the past 6 months or grade 1 within the past 28 days
• No history of either thrombosis or hemorrhage, including hemorrhagic or thrombotic stroke, or other CNS bleeding
• No serious nonhealing wound, ulcer, or bone fracture
• No other prior malignancy except for the following:

• Adequately treated basal cell or squamous cell skin cancer
• Adequately treated stage I or II cancer from which the patient is currently in complete remission
• In situ cervical cancer
• Any other cancer from which the patient has been disease-free for 5 years

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 7 days since prior fine-needle aspiration or core biopsy
• At least 28 days since prior radiotherapy (14 days for palliative radiotherapy) and recovered
• At least 28 days since prior surgery (e.g., thoracic or other major surgeries) and recovered
• At least 28 days since prior systemic chemotherapy
• Prior biologic therapy allowed
• No prior gefitinib, erlotinib hydrochloride, bevacizumab, or other targeted therapies against the epidermal growth factor receptor or vascular endothelial growth factor axes
• Concurrent stable, therapeutic anticoagulation therapy allowed (e.g., warfarin or low molecular weight heparin), provided the patient has no history of bleeding complications on anticoagulation or an inability to establish a stable therapeutic regimen for anticoagulation
• No concurrent surgery
• No other concurrent nonprotocol treatment (including chemotherapy, hormonal therapy, biological therapy, or radiotherapy) directed at this cancer