Carboplatin, Bevacizumab and Pemetrexed in Advanced Non Small Cell Lung Cancer

Inclusion Criteria:

* Advanced stage NSCLC (IIIB with malignant pleural effusion; T4 \[on basis on satellite lesion\] N2, 3; or stage IV) excluding squamous cell histology, with measurable or evaluable disease.
* Prior chemotherapy therapy for early stage disease with one regimen is acceptable if it was completed at least 6 months prior to study entry.
* Palliative radiotherapy to painful bony metastases will be permitted prior to study entry if completed prior to initiation of study treatment, and there are no residual sequelae of therapy such as bone marrow suppression.
* Life expectancy of at least 3 months.
* ECOG Performance status 0-1.
* Age 18 or higher.
* Willingness to use appropriate contraception to avoid pregnancy during the study (female patient or female partner of a male patient)
* Patients must have normal organ and marrow function as defined below:

leukocytes greater than or equal to3,000/µl ANC greater than or equal to 1,500/µl platelets greater than or equal to 100,000/µl total bilirubin within normal institutional limits AST(SGOT)/ALT(SGPT) ≤ 2.5 x institutional upper limit of normal creatinine within normal institutional limits OR creatinine clearance ≥ 45 mL/min/1.73 m2 for patients with creatinine levels above institutional normal

* Ability to sign informed consent
* Ability to take folic acid, Vitamin B12 and dexamethasone as per protocol
* Ability to interrupt NSAIDS 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of Alimta.

Exclusion criteria

Patients meeting any of the following criteria are ineligible for study entry:

* Prior cytotoxic treatment for advanced NSCLC. One prior regimen (up to 4 cycles) of neoadjuvant or adjuvant therapy for early stage disease will be allowed if completed at least 6 months prior to study entry.
* Prior definitive chest irradiation (radiation of rib or spine mets permitted)
* Known brain metastases (unless previously resected and radiated)
* Prior treatment with bevacizumab or pemetrexed
* History of allergic reactions or sensitivity attributed to compounds of similar chemical or biologic composition to bevacizumab or carboplatin
* Current, recent (within 4 weeks of the first infusion of this study), or planned participation in any other experimental drug study.
* Concomitant chemotherapy, radiotherapy or investigational agents.
* Evidence of bleeding diathesis or coagulopathy.
* Use of anti-coagulant agents warfarin (1mg, by mouth, daily for port maintenance permitted), heparin (ASA, NSAID permitted).
* Pregnant (positive pregnancy test) or lactating women.
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study.
* Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to day 0.
* Urine protein creatinine ratio 1.0 at screening. -History of abdominal fistula, gastrointestinal perforation, or intra- abdominal abscess within 6 months prior to Day 0.
* Serious, non-healing wound, ulcer, or bone fracture.
* Lung carcinoma of squamous cell histology or any histology in close proximity to a major vessel, or with significant cavitation as assessed by treating investigator in consultation with an attending radiologist. -Recent history of hemoptysis (bright red blood of 1/2 teaspoon or more)- within one month of study entry
* Significant co-morbidities including:

Blood pressure of 150/100 mmHg Unstable angina New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix B) History of myocardial infarction within 6 months History of stroke within 6 months Clinically significant peripheral vascular disease

* Psychiatric illness/social situations that would limit compliance with study requirements.
* Another active malignancy except for non-melanoma skin cancers.
* Clinically significant pleural, pericardial, and/or peritoneal effusions unless drained or controlled prior to study entry.
* Undrainable, clinically relevant effusions and presence of third space fluid which cannot be controlled by drainage.
* Hepatic impairment as evidenced by Bilirubin greater than 1.5 times the upper limit of normal Transaminases greater than 3.0 times limit of normal (ULN), except in presence of known hepatic metastasis, wherein may be up to 5 times ULN
* Any CTCAE Version 3.0 Grade 3 or 4 non hematologic toxicity