This is a phase II, single institution trial for patients with clinical Stage IB-IIIA NSCLC
(T1-3N0-2M0) who have resectable lung tumors. The primary goal of this study is to show
that the addition of bevacizumab to a cisplatin-based chemotherapy in the neoadjuvant
setting for non-squamous cell carcinomas improves the rate of pathologic downstaging, which
correlates with survival. Downstaging is defined as any decrease in the final pathologic
stage compared with the clinical stage before induction therapy.
- Pathologic confirmation of NSCLC at Memorial Sloan-Kettering Cancer Center (MSKCC)
- Stages IB, IIA, IIB or IIIA (T1-3N0-2M 0) NSCLC
- Patients must be candidates for resection with curative intent.
- Measurable disease, defined as at least one lesion that can be accurately measured in
at least two dimensions
- Age >= 18 years
- Karnofsky performance status >= 70%
- Normal marrow function: leukocytes >= 3,000/µl; absolute neutrophil count ≥ 1,500µl;
platelets >= 100,000 µl; hemoglobin >= 9gm/dl.
- Adequate renal function, with creatinine <= 1.3 mg/dl or calculated creatinine
clearance >= 60ml/min by Cockcroft-Gault equation using parameters of age, weight
(kg), and baseline serum creatinine (mg/dl)
- Adequate hepatic function: total bilirubin within normal limits; AST <= 1.5 X upper
limit of normal (UNL); ALT <= 1.5 X UNL; alkaline phosphatase <= 1.5 X UNL.
- Women of childbearing age must have a negative urine or blood pregnancy test.
- Men and women of childbearing potential must be willing to consent to using effective
contraception while on treatment and for at least 3 months thereafter.
- Patients must have ability to understand and the willingness to sign a written
informed consent document.
- Eligibility criteria for group B: Patients with SQUAMOUS CELL carcinoma or patients
with a NON-SQUAMOUS CELL tumor with a large central tumor in proximity to significant
blood vessels or any history of hemoptysis will be assigned to group B (preoperative
chemotherapy alone without bevacizumab).
- Prior chemotherapy or radiation therapy for NSCLC
- Prior treatment with bevacizumab or other agents specifically targeting vascular
endothelial growth factor (VEGF)
- Patients with a history of severe hypersensitivity reaction to docetaxel (Taxotere)
or other drugs formulated with polysorbate 80
- Patients with known hypersensitivity to other recombinant human antibodies
- Patients must not be receiving any other investigational agents.
- History of stroke or transient ischemic attack (TIA).
- History of myocardial infarction or unstable angina within the past 12 months.
- Patients who report a hearing deficit at baseline, even if it does not require a
hearing aid or intervention, or interfere with activities of daily life (Common
Terminology Criteria for Adverse Events [CTCAE] grade 2 or higher)
- Peripheral neuropathy > grade 1.
- Uncontrolled hypertension
- Esophageal varices, non-healing ulcer, wound, or bone fracture
- Known HIV-positive patients receiving combination anti-retroviral therapy are
excluded from the study because of possible pharmacokinetic interactions with the
- Other serious illness or medical condition including unstable cardiac disease
requiring treatment, history of significant neurologic or psychiatric disorders
(including psychotic disorders, dementia, or seizures), symptomatic diverticulitis,
or active uncontrolled infection.
- Women who are pregnant or breast-feeding
- Psychiatric illness or social situation that would limit compliance with study
- Exclusion criteria for group A: Patients with SQUAMOUS CELL carcinoma, large central
tumor in proximity to significant blood vessels, or any history of hemoptysis (will
be excluded from group A (preoperative chemotherapy plus bevacizumab); these patients
will be assigned to group B (preoperative chemotherapy).