A Phase II Study of Pemetrexed Disodium (ALIMTA®) Plus Bevacizumab in Patients With Stage IIIB Pleural Effusion or Stage IV Non-Small Cell Lung Cancer (Second-Line Treatment)
A Phase II Study of Pemetrexed Disodium (ALIMTA®) Plus Bevacizumab in Patients With Stage IIIB Pleural Effusion or Stage IV Non-Small Cell Lung Cancer (Second-Line Treatment)
RATIONALE: Drugs used in chemotherapy, such as pemetrexed disodium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving pemetrexed disodium together with bevacizumab may be an effective treatment for non-small cell lung cancer.
PURPOSE: This phase II trial is studying how well giving pemetrexed disodium together with bevacizumab works in treating patients with stage III or stage IV non-small cell lung cancer.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is an open-label, multicenter study.
Patients receive pemetrexed disodium IV over 10 minutes and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for 5 years.
DISEASE CHARACTERISTICS:
Histologically or cytologically diagnosed stage IIIB or IV non-small cell lung cancer
Stage IIIB patients must have pleural effusion
Mixed histology allowed if all components consistent with non-small cell lung cancer
Tumors with squamous cell histology feature are allowed
Must have measurable disease with at least one lesion with a longest diameter accurately measured as ≥ 2.0 cm with conventional techniques or as ≥ 1.0 cm with spiral CT
Large ( > 4 cm) centrally located lesions or large lesions in close proximity to major blood vessels should receive palliative radiation
Previously treated with one chemotherapy regimen in the neoadjuvant, adjuvant, or advanced disease setting
No symptomatic, untreated, or uncontrolled CNS metastases
PATIENT CHARACTERISTICS:
ECOG performance status 0-2
Life expectancy ≥ 12 weeks
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/ mm^3
Hemoglobin ≥ 9 g/dL
Bilirubin ≤ 1.5 times upper limit of normal (ULN) or direct bilirubin normal
AST and ALT ≤ 3 times ULN (5 times ULN if liver has tumor involvement)
Creatinine clearance ≥ 45 mL/min
Urine protein:creatinine ratio < 1.0
Pregnant or nursing women are ineligible
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after study participation
No seizure disorder
No clinically significant infection
No other second primary malignancy within the past 5 years except carcinoma in situ of the cervix, non-melanomatous skin cancer, or low-grade (Gleason score ≤ 6) localized prostate cancer
No hypertension or labile hypertension
No history of poor compliance with antihypertensive medications
No angina pectoris
No congestive heart failure within the past 3 months unless ejection fraction > 40%
No myocardial infarction within the past 6 months
No cardiac arrhythmia
No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
No active or recent history of hemoptysis
No diabetes
No prior serious, non-healing wounds, ulcers, or bone fractures
No history of stroke within the past 6 months
No history of abdominal fistula or gastrointestinal perforation
No intra-abdominal abscess within the past 6 months
Not at greater than average risk of bleeding
No significant traumatic injury within the past 4 weeks
PRIOR CONCURRENT THERAPY:
No aspirin at doses ≥ 1.3 grams per day within 10 days prior to or 10 days after pemetrexed disodium treatment
No chemotherapy within the past 3 weeks (6 weeks for mitomycin C or nitrosoureas)
No immunotherapy or biologic therapy within the past 2 weeks
No full field radiation therapy within the past 4 weeks or limited field radiation therapy within the past 2 weeks
No prior post pelvic radiation
No prior use of pemetrexed disodium
No prior radiation to > 25% of the marrow cavity
No major surgery (i.e., laparotomy) or open biopsy within the past 4 weeks
No minor surgery within the past 2 weeks except insertion of a vascular access device
No concurrent major surgery
No other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, or any ancillary therapy considered investigational within the past 4 weeks
No concurrent use of Hypericum perforatum (St. John's wort)
No concurrent anticoagulant use
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