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