This Phase II, multicenter, randomized trial is designed to make preliminary evaluations of the efficacy of combining bevacizumab with chemotherapy (docetaxel or pemetrexed) or Tarceva relative to chemotherapy (docetaxel or pemetrexed) alone in patients with previously treated advanced NSCLC.
Inclusion Criteria:
* Signed written informed consent
* Histologically or cytologically proven Stage IIIb with pleural effusion, or Stage IV, recurrent non-squamous NSCLC that is recurrent and unresectable
* Progression after one line of platinum-based chemotherapy (patients who have received prior docetaxel treatment are eligible to participate if there are no contraindications for pemetrexed treatment)
* Progression after previous adjuvant chemotherapy, if therapy was completed >= 6 months prior to randomization and the patient has received one line of therapy for recurrent disease
* (Optional) Availability of archival diagnostic tissue (paraffin tissue block or 2-10 unstained slides representative of the patient's primary cancer)
* ECOG performance status of 0, 1, or 2
* Life expectancy >= 3 months
* Measurable disease in accordance with RECIST
* Age >= 18 years
* Use of an acceptable means of contraception (potentially fertile men and women) or documentation of infertility
Exclusion Criteria:
* More than 30 days of prior treatment with an investigational or marketed agent that acts by EGFR inhibition (those with 30 or fewer days on an EGFR inhibitor without disease progression are eligible for enrollment)
* Treatment with an investigational or marketed agent that acts by anti-angiogenic mechanisms
* Previous treatment with more than one platinum-based chemotherapy
* Chemotherapy or radiotherapy within 28 days prior to randomization
* History of hemoptysis (> 1 teaspoon) or presence of a cavitary lesion
* Clinical history of Grade > 2 hematemesis within 6 months or Grade 1 hematemesis within 28 days prior to randomization
* History of serious systemic disease, including myocardial infarction within the last 6 months, uncontrolled hypertension (blood pressure > 150/100 mmHg on medication), unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure, unstable symptomatic arrhythmia requiring medication (patients with chronic atrial arrhythmia, i. e., atrial fibrillation or paroxysmal supraventricular tachycardia are eligible), or Grade II or greater peripheral vascular disease
* History or clinical evidence of CNS or brain metastases or CNS bleeding
* History or clinical evidence of hemorrhagic or thrombotic stroke within the 6 months prior to randomization
* Centrally located lesions and lesions that abut major blood vessels
* Ongoing treatment with full-dose warfarin (or its equivalent) or heparin (or its equivalent; e. g., Lovenox(R))
* In-patient surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization
* Minor surgical procedure, fine needle aspirations, or core biopsy within 7 days prior to randomization
* Anticipation of need for a major surgical procedure during the course of the study
* Serious, non-healing wound, ulcer, or bone fracture
* Inability to take oral medication or requirement for IV alimentation or total parenteral nutrition with lipids, or prior surgical procedures affecting absorption
* Any of the following abnormal hematologic values (within 1 week prior to randomization): ANC <= 1,500 cells/uL; platelet count <= 100,000 cells/uL; Hemoglobin <= 9. 0 g/dL; International normalized ratio (INR) > 1. 5 x upper limit of normal (ULN)
* For patients who will receive docetaxel, any of the following abnormal liver function tests (within 1 week prior to randomization): Serum bilirubin greater than ULN; Albumin <= 2. 5 g/dL; Serum ALT >= 1. 5 x ULN; Serum AST >= 1. 5 x ULN; Alkaline phosphatase >= 2. 5 x ULN
* Other baseline laboratory values: Serum creatinine > 2. 0 x ULN; Uncontrolled hypercalcemia ( > 11. 5 mg/dL); Urinary protein/creatinine ratio >= 1 (spot urine) or clinically significant impairment of renal function; Estimated creatinine clearance < 45 mL/min (for patients who will receive pemetrexed)
* Any active systemic bacterial, fungal, or viral infection, including known hepatitis C and HIV
* Pregnant or breast-feeding
* Presence of another cancer within 5 years prior to randomization, except for adequately treated carcinoma in situ of the cervix or non-melanomatous skin cancer
* Evidence of confusion or disorientation, or history of major psychiatric illness that may impair the patient's understanding of the Informed Consent Form
California Cancer Center, Inc, Greenbrae, California 94904, United States
Kaiser Permanente/ San Diego, San Diego, California 92120, United States
Sansum Santa Barbara Medical Foundation Clinic (TORI), Santa Barbara, California 93105, United States
North Valley Hematology/Oncology Medical Group (TORI), Northridge, California 91328, United States
Comprehensive Blood and Cancer Center (TORI), Bakersfield, California 93309, United States
Ventura County Hematology-Oncology Specialists (TORI), Oxnard, California 93030, United States
Central Hematology Oncology Medical Group (TORI), Monterey Park, California 91754, United States
Wilshire Oncology Medical Group (TORI), Laverne, California 91750, United States
Santa Barbara Hematology Oncology Medical Group, Inc (TORI), Santa Barbara, California 93105, United States
Pacific Shores Medical Group (TORI), Long Beach, California 90813-3244, United States
Virginia K. Crosson Cancer Center (TORI), Fullerton, California 92835, United States
Cancer Care Associates Medical Group (TORI), Redondo Beach, California 90277, United States
San Diego Cancer Center Medical Group (TORI), Vista, California 92081, United States
UC Davis Cancer Center, Sacramento, California 95817, United States
Bay Area Cancer Research Group, Concord, California 94520, United States
UCLA Medical Center PVUB 3360, Los Angeles, California 90095, United States
Kaiser Permanente Northern CA, Vallejo, California 94589, United States
Florida Cancer Specialists, Fort Myers, Florida 33901, United States
The Florida Cancer Institute(TORI), Orlando, Florida 32804, United States
Comprehensive Cancer Care Specialist at Boca Raton, Boca Raton, Florida 33428, United States
MD Anderson Cancer Ctr- Orlando, Orlando, Florida 32806, United States
Atlanta Cancer Care (TORI), Roswell, Georgia 30076, United States
Suburban Hematology-Oncology Associates (TORI), Lawrenceville, Georgia 30045, United States
Medical Oncology Associates, PC (TORI), Augusta, Georgia 30901, United States
WellStar Cancer Research Office, Marietta, Georgia 30060, United States
Hematology and Oncology of Northeast Georgia, PC (TORI), Athens, Georgia 30607, United States
University of Chicago, Chicago, Illinois 60637, United States
Hematology Oncology Consultants, Naperville, Illinois 60540, United States
Loyola Univ. Medical Center, Maywood, Illinois 60153, United States
Rush-Presbyteriam, Chicago, Illinois 60612, United States
Oncoloy Hematology Associates of Central Illinois, PC (TORI), Peoria, Illinois 61615, United States
Norton Healthcare Louisville Oncology, Louisville, Kentucky 40202, United States
Ochsner Cancer Inst., New Orleans, Louisiana 70121, United States
Maine Center for Cancer Medicine and Blood Disorders, Scarborough, Maine 04074, United States
Methodist Cancer Center-Oncology Research, Omaha, Nebraska 68114, United States
Comprehensive Cancer Centers of Nevada (TORI), Las Vegas, Nevada 89109, United States
Summit Medical Group Overlook Oncology Center, Summit, New Jersey 07901, United States
Cancer Research of Long Island, Great Neck, New York 11023, United States
Northwestern Carolina Oncology and Hematology, Hickory, North Carolina 28603, United States
Mid Dakota Clinic, Bismarck, North Dakota 58501, United States
Earle A. Chiles Research Institute, Portland, Oregon 97213, United States
Kaiser Permanente Northwest Region, Portland, Oregon 97227, United States
Univ. of Pittsburgh Cancer Center Inst., Pittsburgh, Pennsylvania 15232, United States
The West Cancer Clinic, Memphis, Tennessee 38120, United States
University of Tenn. Cancer Ins, Memphis, Tennessee 38104, United States
M.D. Anderson, Houston, Texas 77030, United States
Virginia Mason Medical Center, Seattle, Washington 98101, United States
Internal Medicine Associates of Yakima, Yakima, Washington 98902, United States
