BLP25 Liposome Vaccine and Bevacizumab After Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Stage IIIA or Stage IIIB Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery

OBJECTIVES:

Primary

- To determine the safety of BLP25 liposome vaccine (tecemotide) and bevacizumab after
definitive chemoradiotherapy and consolidation chemotherapy in patients with newly
diagnosed, unresectable stage IIIA or IIIB nonsquamous cell non-small cell lung cancer.

Secondary

- To evaluate the overall survival and progression-free in patients treated with this
regimen.

- To evaluate the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

Step 1:

- Chemoradiotherapy: Patients receive paclitaxel intravenously (IV) over 1 hour and
carboplatin IV over 15-30 minutes once a week for 6 weeks. Patients also undergo
concurrent definitive radiotherapy 5 days a week for 6½ weeks. Patients with complete
response (CR), partial response (PR), or stable disease (SD) proceed to consolidation
chemotherapy.

- Consolidation chemotherapy: Patients receive paclitaxel IV over 3 hours and carboplatin
IV over 15-30 minutes on day 1. Treatment repeats every 21 days for 2 courses in the
absence of disease progression or unacceptable toxicity. Patients with CR, PR, or SD
proceed to maintenance therapy.

Step 2:

- Maintenance therapy: Patients receive a single dose of cyclophosphamide IV over 15-30
minutes 3 days before the first dose of bevacizumab and BLP25 liposome vaccine. Patients
then receive bevacizumab IV over 30-90 minutes on day 1 and BLP25 liposome vaccine
subcutaneously on days 1, 8, and 15 of courses 1 and 2 and on day 1 of every other
course beginning in course 4. Treatment repeats every 21 days for up to 34 courses in
the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 5 years.

Step 1 Inclusion Criteria:

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

- Adenocarcinoma

- Large cell undifferentiated

- Bronchoalveolar cell

- non-small cell carcinoma, 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 computerized tomography (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 Response Evaluation Criteria in
Solid Tumours (RECIST) criteria

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1

- White blood cell (WBC) ≥ 4,000/mm³ OR Absolute neutrophil count (ANC) ≥ 2,000/mm³

- Platelet count ≥ 140,000/mm³

- Hemoglobin ≥ 9.0 g/dL

- Total bilirubin ≤ 1.5 mg/dL

- Aspartate aminotransferase (AST)/alanine aminotransferase (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

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

Step 1 Exclusion Criteria:

- Significant pleural effusion

- CNS metastases by head CT scan or MRI within the past 4 weeks

- Pregnant or breast-feeding

- Prior chemotherapy or monoclonal antibodies for other cancers within 5 years prior to
registration

- Prior chemotherapy for lung cancer

- Prior chest radiotherapy

- Ongoing (lasting > 14 days) or active infection or ongoing (lasting > 14 days) fever
within the past 6 months

- Gross hemoptysis ≥ grade 2 (defined as ≥ ½ teaspoon of bright red blood per episode)
within the past 3 months

- Bleeding ≥ grade 2 or any bleeding requiring intervention

- 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

- Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the
past 6 months

- Psychiatric illness or social situation that would limit compliance with study
requirements

- History of uncontrolled hypertension (i.e., blood pressure ≥ 150/100 mm Hg) while on
stable regimen of antihypertensive therapy

- Significant traumatic injury or serious non-healing wound, ulcer, or bone fracture
within the past 4 weeks

- Concurrent major surgical procedure

- Having anticipated major surgical procedure(s) during the course of the study

- Concurrent daily aspirin (> 325 mg/day) or nonsteroidal anti-inflammatory agents
(NSAIDs) known to inhibit platelet function

- Recognized immunodeficiency disease, including cellular immunodeficiencies,
hypogammaglobulinemia or dysgammaglobulinemia, or hereditary or congenital
immunodeficiencies

- Pre-existing medical condition requiring chronic steroids or immunosuppressive therapy

- Autoimmune disease

- Known hepatitis B or C

- Immunotherapy (e.g., interferon, interleukin, sargramostim [GM-CSF], or filgrastim
[G-CSF]) within 28 days prior to registration

- Prior splenectomy

- Hypersensitivity to any component of bevacizumab

- Prior core biopsy or any other minor surgical procedure, excluding the placement of a
vascular access device, within 7 days prior to registration

Step 2 Inclusion Criteria:

- Serum creatinine ≤ 1.5 mg/ml or calculated creatinine clearance ≥ 45 ml/min

- Urine dipstick must be ≤ 0-1+. If urine dipstick results > 1+, 24 hour urine for
protein must be obtained. Patients must have < 1g protein/24 hours to participate in
the study

- Patient must be registered to step 2 within 28 days of completion of consolidation
chemotherapy

- Patient must have met all eligibility requirements for Step 1

- Platelets ≥ 100,000/mm3

Step 2 Exclusion Criteria:

- Progressive disease or unevaluable disease per RECIST criteria upon post-
consolidation chemotherapy evaluation

- Autoimmune disease