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)

Histologic or cytologically proven Stage IV NSCLC or Stage III NSCLC with pleural effusion. Mixed histology if all components consistent with NSCLC. Pts with large (>4cm) central lesions or large lesions close to blood vessels should receive palliative radiation prior to. Irradiated lesion cannot be target. Previously treated with one chemotherapy regimen as neoadjuvant, adjuvant therapy, or advanced disease. Prior radiation allowed if: recovery from toxic radiation effect before study entry (except for alopecia); </= 25% of marrow-containing skeleton radiated; measurable disease or proof of progressive disease since radiation is outside port. Pts must have measurable disease as defined in Section 11.0 with at least one lesion with a longest diameter >/=2.0cm measured using conventional techniques, or >/= 1.0cm spiral CT measured. ECOG PS 0,1,or 2. Lab values obtained </= 14d prior: ANC >/=1500mcl; PLT>/=100,000mcl; Hgb>=9g/dL; total bilirubin</=1.5xULN OR direct bilirubin </= ULN; AST and ALT </=3x ULN OR AST and ALT</=5x ULN (if tumor involvement in liver); calc. creat. clear. >/=45ml/min using Gault formula AND urine protein: creat. ratio<1.0. Pts must be able to take folic acid, vitamin B12, or dexamethasone. Able to d/c aspirin of >/= 1.3gms/day >/=10d before or after treated with pemetrexed. Life expectancy of >/=12wks. Willingness to return for follow-up. Willingness to provide biologic specimens. No pregnant or nursing women. No symptomatic, untreated, uncontrolled CNS mets or seizure disorder. Pts with CNS mets treated with WBRT may be enrolled after treatment. No significant infection. No second primary malignancy except carcinoma in situ of the cervix or non-melanomatous skin cancer, unless prior malignancy diagnosed and treated </=5years previous with no evidence of recurrence. Pts with history of low-grade localized prostate cancer eligible even if diagnosed <5years prior to. Pts must not have had any therapies outlined in Section 3.25 or medical conditions in Section 3.27. No chemotherapy, immunotherapy, hormonal therapy, radiotherapy, or any ancillary therapy considered investigational </=4wks prior to. No non-healing wounds, bone fractures, ulcers. Effusion must be amenable to drainage. No history of stroke </=6mo. prior to. Pts must not be at abnormal risk for bleeding or on any anticoagulation except those receiving low dose warfarin or heparin for deep vein thrombosis prophylactically. No history of abdominal fistula, GI perforation, intra-abdominal abscess </=6mo. prior to. No prior use of pemetrexed, St. John’s Wort. No serious condition that would prevent pt from completing study.