Phase II Trial of Carboplatin and Pemetrexed Plus Bevacizumab in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically* or cytologically* confirmed non-small cell lung cancer

- Any histology, except squamous cell carcinoma, allowed

- Mixed tumors will be categorized by the predominant cell type unless small
cell elements are present, in which case the patient is ineligible

- No histology in close proximity to a major vessel or cavitation NOTE:
*Histologic or cytologic elements may be established on metastatic tumor
aspirates or biopsy

- Meets 1 of the following stage criteria:

- Stage IIIB disease (with malignant pleural effusion)

- Stage IV disease

- Recurrent disease

- Measurable or non-measurable disease

- No known CNS metastases by CT scan or MRI

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-1

Life expectancy

- Not specified

Hematopoietic

- Absolute neutrophil count > 1,500/mm^3

- Platelet count > 100,000/mm^3

- No history of hemorrhagic disorders

Hepatic

- Bilirubin < 1.5 mg/dL

- AST and ALT < 5 times upper limit of normal

- INR < 1.5

- PTT normal

Renal

- Creatinine clearance ≥ 45 mL/min

- Urine protein:creatinine ≤ 1.0 by spot urinalysis

Cardiovascular

- No myocardial infarction within the past 6 months

- No New York Heart Association class II-IV congestive heart failure

- No unstable angina pectoris

- No serious cardiac arrhythmia requiring medication

- No stroke within the past 6 months

- No peripheral vascular disease ≥ grade 2

- No uncontrolled hypertension (i.e., blood pressure ≥ 150/100 mm Hg)

- Patients with a history of hypertension allowed provided blood pressure is well
controlled on a stable regimen of anti-hypertensive therapy

- No history of thrombotic disorders

- No other clinically significant cardiovascular disease

Pulmonary

- No history of gross hemoptysis, defined as bright red blood of a ½ teaspoon or more

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Must be willing and able to take daily oral folic acid, intermittent vitamin B_12
injections, and corticosteroid premedication

- No ongoing or active infection

- No serious, non-healing wound, ulcer, or bone fracture

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

- No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

- More than 3 weeks since prior immunotherapy

Chemotherapy

- No prior systemic chemotherapy

Endocrine therapy

- More than 3 weeks since prior hormonal therapy

Radiotherapy

- See Disease Characteristics

- More than 3 weeks since prior radiotherapy

Surgery

- More than 4 weeks since prior major surgery

- More than 1 week since prior minor surgery, fine needle aspiration, or core biopsy

- No concurrent major surgery

Other

- Recovered from all prior therapy

- More than 4 weeks since prior and no concurrent participation in another experimental
drug study

- No aspirin or other nonsteroidal anti-inflammatory drug (NSAID) 2 days before and 2
days after each pemetrexed disodium infusion (5 days before and 2 days after each
pemetrexed disodium infusion for NSAIDs with a long half-life [e.g., naproxen,
rofecoxib, or celecoxib])

- No concurrent therapeutic anticoagulation

- Concurrent prophylactic anticoagulation for venous access devices allowed
provided requirements for INR and PTT are met

- No concurrent administration of any of the following:

- Chronic daily treatment with aspirin (> 325 mg per day)

- NSAIDs known to inhibit platelet function, including any of the following:

- Dipyridamole

- Ticlopidine

- Clopidogrel

- Cilostazol