A Phase II Study of L-BLP25 and Bevacizumab in Unresectable Stage IIIA and IIIB Non-Squamous Non-Small Cell Lung Cancer After Definitive Chemoradiation

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed newly diagnosed nonsquamous cell non-small cell lung cancer
(NSCLC), including the following subtypes:

- Adenocarcinoma

- Large cell undifferentiated

- Bronchoalveolar cell

- NSCLC, not otherwise specified

- Unresectable stage IIIA or stage IIIB disease

- Patients with stage IIIA disease with mediastinal lymph node enlargement between
1 cm and 2.0 cm on CT scan must have these nodes biopsied (pathologic
confirmation) to rule out resectability

- Metastases to contralateral mediastinal or supraclavicular nodes allowed

- Measurable or non-measurable disease, as defined by RECIST criteria

- No significant pleural effusion as defined by either of the following:

- Pleural effusion is seen on CT scan only (not seen on chest x-ray)

- Pleural effusion does not reaccumulate within 1 week after thoracentesis AND is
cytologically negative

- No CNS metastases by head CT scan or MRI within the past 4 weeks

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- WBC ≥ 4,000/mm³ OR ANC ≥ 2,000/mm³

- Platelet count ≥ 140,000/mm³

- Hemoglobin ≥ 9.0 g/dL

- Total bilirubin ≤ 1.5 mg/dL

- AST/ALT ≤ 2.5 times upper limit of normal

- Serum creatinine ≤ 1.5 mg/mL OR creatinine clearance ≥ 45 mL/min

- Urine protein:creatinine ratio < 1.0 by urine dipstick OR < 1 g of protein by 24-hour
urine collection

- INR ≤ 1.5 OR ≤ 3.0 if patient is on therapeutic anticoagulation

- PTT normal

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception before, during, and for ≥ 6 months
after completion of bevacizumab

- No other active malignancies

- No known hepatitis B or C

- No ongoing (lasting > 14 days) or active infection or ongoing (lasting > 14 days)
fever within the past 6 months

- No gross hemoptysis ≥ grade 2 (defined as ≥ ½ teaspoon of bright red blood per
episode) within the past 3 months

- No pulmonary hemoptysis

- Confirmed extrapulmonary hemoptysis allowed

- No bleeding ≥ grade 2 or any bleeding requiring intervention

- No history of bleeding diathesis or coagulopathy

- No cardiac dysfunction, including any of the following:

- Clinically significant cardiovascular disease

- Myocardial infarction within the past 6 months

- New York Heart Association class III-IV congestive heart failure

- Unstable angina pectoris

- Serious cardiac arrhythmia requiring medication within the past 4 weeks

- History of hypertensive crisis or hypertensive encephalopathy

- Stroke or transient ischemic attack within the past 6 months

- Peripheral vascular disease ≥ grade 2 within the past 6 months

- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
the past 6 months

- No psychiatric illness or social situation that would limit compliance with study
requirements

- No history of uncontrolled hypertension (i.e., blood pressure ≥ 150/100 mm Hg) while
on stable regimen of antihypertensive therapy

- No significant traumatic injury or serious non-healing wound, ulcer, or bone fracture
within the past 4 weeks

- No recognized immunodeficiency disease, including cellular immunodeficiencies,
hypogammaglobulinemia or dysgammaglobulinemia, or hereditary or congenital
immunodeficiencies

- No pre-existing medical condition requiring chronic steroids or immunosuppressive
therapy

- No autoimmune disease

- No known hypersensitivity to any component of bevacizumab

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- More than 4 weeks since prior open biopsy or major surgical procedure

- More than 28 days since prior immunotherapy (e.g., interferon, interleukin,
sargramostim [GM-CSF], or filgrastim [G-CSF])

- Patients must not have had prior chemotherapy or monoclonal antibodies for other
cancers within 5 years prior to registration

- More than 7 says since prior core biopsy or any other minor surgical procedure,
excluding the placement of a vascular access device

- No prior chemotherapy for lung cancer

- No prior chest radiotherapy

- No prior splenectomy

- Concurrent stable regimen of therapeutic anticoagulation or prophylactic
anticoagulation for venous access devices allowed provided coagulation studies met
entry criteria

- No concurrent daily aspirin (> 325 mg/day) or nonsteroidal anti-inflammatory agents
(NSAIDs) known to inhibit platelet function

- No concurrent dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel bisulfate
(Plavix), and/or cilostazol (Pletal)

- No concurrent major surgical procedure