Ixabepilone and Carboplatin +/- Bevacizumab in Advanced Non-Small-Cell Lung Cancer

Inclusion Criteria:

1. Histologically confirmed non-small-cell bronchogenic carcinoma (squamous carcinoma, adenocarcinoma, or large cell carcinoma). Cytologic specimens obtained by brushings, washings, or needle aspiration of the defined lesion are acceptable. Mixed tumors with small-cell anaplastic elements are not eligible.
2. Patients who have newly diagnosed unresectable stage III or IV disease are eligible. Patients with stage III disease should be ineligible for combined modality therapy
3. Patients must not have received any prior antineoplastic chemotherapy for metastatic lung cancer prior to study entry.
4. Patients who have had previous radiotherapy as definitive therapy for locally advanced non-small-cell are eligible as long as the recurrence is outside the original radiation port. Radiation therapy must have been completed greater than 4 weeks prior to registration.
5. Male or female patients \>=18 years of age.
6. Life expectancy of at least 3 months.
7. ECOG performance status of \<=1.
8. Measurable disease by RECIST criteria (see Section 7).
9. Laboratory values as follows:

   * ANC \>=1500/mm3 (7 days prior to treatment);
   * Hemoglobin \>=8 g/dL;
   * Platelets \>=100,000 mm3 (7 days prior to treatment)
   * Bilirubin \<=1 x ULN for institution
   * AST/SGOT \<=2.5 x ULN or \<=5.0 x ULN in patients with liver metastases and
   * ALT/SGPT \<=2.5 x ULN or \<=5.0 x ULN in patients with liver metastases
   * Creatinine \<=2.0 mg/dL or
   * Calculated (measured) GFR \>=40 mL/min
   * PT/INR and PTT \<=1.5 x ULN
10. Peripheral neuropathy \<= grade 1.

Exclusion Criteria:

1. A history of cardiac disease as defined by malignant hypertension, unstable angina, congestive heart failure of \> grade 2 per New York Heart Association (NYHA) criteria (see Appendix B), myocardial infarction within the previous 6 months, or symptomatic cardiac arrhythmias.
2. Metastatic brain or meningeal tumors.
3. Uncontrolled intercurrent illness.
4. Chemotherapy, investigational drug therapy, or major surgery ≤ 4 weeks prior to starting study drug, or patients who have not recovered from side effects of previous therapy.
5. Patient is \<=5 years free of another primary malignancy, except if the other primary malignancy is not currently clinically significant or requiring active intervention, or if the other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ.

Exclusion Criteria for Enrollment on Bevacizumab (Cohort B):

1. Patients with squamous cell histology NSCLC.
2. Patients who have had a major surgical procedure (not including mediastinoscopy), open biopsy, or significant traumatic injury within 1 month of beginning bevacizumab.
3. Patients who have had primary thoracic radiation within 3 months of beginning bevacizumab.
4. Fine needle aspiration, core biopsy, mediastinoscopy or other minor surgical procedure within 7 days of beginning bevacizumab.
5. Patients receiving thrombolytic therapy within 10 days of starting bevacizumab.
6. Patients with serious non-healing wound, ulcer, or bone fracture.
7. Patients with evidence of bleeding diathesis or coagulopathy.
8. Patients with history of hemoptysis (defined as bright red blood of ½ teaspoon or more per episode) within 3 months prior to study enrollment.
9. Patients with proteinuria at screening, as demonstrated by either:

   * Urine protein : creatinine (UPC) ratio \>=1.0 or
   * Urine dipstick for protein \>=2+ (patients discovered to have \>=2+ proteinuria on dipstick at baseline should undergo a 24-hour urine collection, and must demonstrate \<1 g of protein in 24 hours to be eligible).
10. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to beginning bevacizumab.