A Phase III Randomized Trial of Adjuvant Chemotherapy With or Without Bevacizumab for Patients With Completely Resected Stage IB (> 4cm)-IIIA Non-Small Lung Cancer (NSCLC)

Inclusion Criteria:

- Diagnosis of stage IB-IIIA (T2-3 N0, T1-3 N1, T1-3 N3) non-small cell lung cancer
(NSCLC)

- Patients with stage IB disease must have tumors measuring ≥ 4 cm

- No non-squamous cell histology (for patient assigned to receive the pemetrexed
disodium and cisplatin therapy)

- Must have undergone complete resection of NSCLC within the past 6-12 weeks

- Accepted types of resection include any of the following:

- Lobectomy

- Sleeve lobectomy

- Bilobectomy

- Pneumonectomy

- No resection by segmentectomy or wedge resection

- Mediastinal lymph node sampling at specific levels is required pre-operatively
(mediastinoscopy) or intraoperatively (level 7 for right-sided tumors or level 7 and
5 and/or 6 for left sided tumors)

- ECOG performance status 0-1

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- INR ≤ 1.5 OR INR ≤ 3.0 with therapeutic anticoagulation

- PTT normal OR PTT ≤ 1.5 times upper limit of normal (ULN) for patients on therapeutic
anticoagulation

- Bilirubin ≤ 1.5 mg/dL

- AST and ALT < 5 times ULN

- Creatinine ≤ 1.5 times ULN

- Creatinine clearance ≥ 45 mL/min (for patient assigned to receive the pemetrexed
disodium and cisplatin therapy)

- If urine protein: creatinine ratio > 0.5, then urine protein must be < 1,000 mg by
24-hour urine collection

- No other cancer within the past 5 years except in situ carcinoma of the cervix or
completely resected nonmelanoma skin cancer

- Known history of myocardial infarction or other evidence of arterial thrombotic
disease (angina) allowed if there is no evidence of active disease within the past 12
months

- No history of cerebrovascular accident or transient ischemic attack

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for at least 6 months
after completion of study treatment

- No clinically significant ongoing, active, or serious infection, symptomatic or
uncontrolled congestive heart failure or cardiac arrhythmia, psychiatric illness or
social situation, or any other medical condition that would preclude study compliance

- No history of bleeding diathesis or coagulopathy

- Systolic blood pressure (BP) ≤ 150 and diastolic BP ≤ 90 within the past 28days

- Patients with known hypertension on a stable regimen of antihypertensive therapy
allowed

- No serious nonhealing wound, ulcer, or bone fracture

- No significant traumatic injury within the past 28 days

- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
the past 28 days

- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies

- No ongoing postoperative hemoptysis (i.e., bright red blood of ≥ ½ teaspoon

- Recovered from prior surgery

- At least 7 days since prior aspirin or non-steroidal anti-inflammatory agents
(NSAIDS), dipyridamole (Persantine), ticlopine (Ticlid),clopidogrel (Plavix) and/or
cilostazol (Pletal)

- No prior systemic chemotherapy

- Prior methotrexate given in low doses for non-malignant conditions with the last
dose ≥ 2 weeks ago is allowed

- Other low-dose chemotherapeutics for non-malignant conditions may be allowed
after review by the study chair

- No hormonal cancer therapy or radiotherapy as cancer treatment within the past 5years

- Prior surgery, biologic therapy, hormonal therapy, or radiotherapy for a
malignancy diagnosed > 5 years prior to study entry that is now considered
cured allowed

- No major surgery or open biopsy within the past 28 days

- No anticipated major surgery during course of treatment

- No core biopsy within the past 7 days

- Concurrent therapeutic anticoagulation therapy allowed

- No concurrent aminoglycoside antibiotics

- No concurrent growth factors