Carboplatin and Gemcitabine With Bevacizumab Every 2 Weeks for Stage IIIb/IV Non-small Cell Lung Cancer

Inclusion Criteria:

* Patients must have histologically or cytologically confirmed non-small cell lung cancer (NSCLC) EXCEPT squamous cell carcinoma or predominantly squamous. Mixed tumors will be categorized by the predominant cell type unless small cell elements are present in which case the patient is ineligible. (Sputum cytology alone is not acceptable)
* Must have disease that is not curative by standard methods.
* Prior adjuvant systemic chemotherapy, immunotherapy, or biological therapy is allowed, except for prior use of bevacizumab. If gemcitabine was used, more than six months must have elapsed between completion of adjuvant therapy and disease progression. Patient must be at least 14 days from previous systemic therapy (at least 30 days for investigational agents) and have recovered from the acute toxic effects of the treatment as determined by the treating physician prior to study registration. Prior therapy other than adjuvant therapy is not allowed.
* Prior radiation therapy must be completed at least 14 days of study registration and subjects must fully recover from acute toxicities as determined by the treating physician. Prior radiation to \> 25% of bone marrow is not allowed. Prior radiation therapy to the whole pelvis is not allowed.
* Disease status must be measurable or non-measurable as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
* ECOG Performance status of 0 or 1
* Age 18 years or greater
* Adequate organ function within 14 days of study registration including the following:

  * Adequate bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L, platelets ≥ 100 x 10\^9/L, hemoglobin ≥ 9 g/dL
  * Hepatic: bilirubin ≤ 1.5 times the upper limit of normal (× ULN), alkaline phosphatase (ALP), aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 × ULN (ALP, AST, and ALT ≤ 5 × ULN is acceptable if liver has tumor involvement)
  * Renal: Adequate renal function as evidenced by creatinine clearance of \> 50ml/min, estimated by the Cockcroft-Gault equation or urine dipstick for proteinuria \< 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible)
  * Coagulation: INR \< 1.5, PTT \< the upper limits of normal (ULN) unless stable on therapeutic anticoagulation at study entry. The addition of anticoagulants after study start is not allowed.
* Women of childbearing potential and sexually active males are required to use an effective method of contraception (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicidal, condom with spermicidal, or abstinence) during the study and for 3 months after the last dose of study drug.
* Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

Exclusion Criteria:

* Intrathoracic lung carcinoma of squamous cell histology. Mixed tumors will be categorized by the predominant cell type unless small cell elements are present, in which case the patient is ineligible; sputum cytology alone is acceptable for inclusion. Subjects with extrathoracic-only squamous cell NSCLC are eligible. Subjects with only peripheral lung lesions of any NSCLC histology will also be eligible. A peripheral lesion is defined as a lesion in which the epicenter of the tumor is \< 2 cm from the costal or diaphragmatic pleura in a three-dimensional orientation based on each lobe of the lung and is \> 2 cm from the trachea, main and lobar bronchi.
* Pregnant (positive pregnancy test within 14 days of study enrollment) or breast-feeding. Gemcitabine and carboplatin are pregnancy category D - clear evidence of risk in pregnancy; bevacizumab is pregnancy category C - risk in pregnancy cannot be ruled out. Pregnancy testing is not required for post-menopausal (defined as absence of menses for the preceding 24 consecutive months) or surgically sterilized women.
* Inadequately controlled hypertension (defined as systolic blood pressure \>150 and/or diastolic blood pressure \> 100 mmHg on antihypertensive medications)
* Any prior history of hypertensive crisis or hypertensive encephalopathy
* New York Heart Association (NYHA) Grade II or greater congestive heart failure
* History of stroke or transient ischemic attack within 6 months prior to study enrollment
* Clinically significant peripheral vascular disease (e.g., aortic aneurysm, aortic dissection)
* Symptomatic peripheral vascular disease
* Evidence of bleeding diathesis or coagulopathy in the absence of therapeutic anticoagulation
* Current or recent (within 10 days of enrollment) use of aspirin (\>325 mg/day) or chronic use of other NSAIDs known to inhibit platelet function Treatment with dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and/or cilostazol (Pletal)
* Requiring therapeutic anticoagulation
* Current, ongoing treatment with full-dose warfarin or its equivalent (i.e., unfractionated and/or low molecular weight heparin)
* History of thrombotic or hemorrhagic disorders
* T4 tumors with invasion of the heart or great vessels
* Presence or history of central nervous system or brain metastases, except for treated brain metastases. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI/CT) during the screening period. Anticonvulsants are allowed, providing the subject is on a stable dose. Treatment for brain metastases may include whole brain radiotherapy, radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. Subjects with CNS metastases treated by radiotherapy within 28 days of Day 1 will be excluded. Subjects treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded.
* History of another malignancy other than NSCLC except in situ carcinoma of the cervix; adequately treated nonmelanomatous carcinoma of the skin; low grade (Gleason score ≤ 6) localized prostate cancer or other prior malignancy treated at least 2 years previously with no evidence of recurrence
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to treatment start, anticipation of need for major surgical procedure during the course of the study
* Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to treatment start
* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to treatment start
* Serious, non-healing wound, ulcer, or bone fracture, or the presence of a serious active infection
* History of hemoptysis defined as bright red blood of 1/2 teaspoon or more in the previous 1 month before enrollment
* Patients with known hypersensitivity to any of the components of carboplatin, gemcitabine or bevacizumab.
* Known HIV or Hepatitis B or C (active, previously treated or both)
* Inability to comply with study and/or follow-up procedures
* Life expectancy \< 12 weeks.