Phase II Trial of Abraxane Plus Carboplatin for Advanced NSCLC for Patients at Risk of Bleeding From VEGF Directed Therapies

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed advanced non-small cell lung cancer (NSCLC)
meeting 1 of the following criteria:

- Stage IIIB disease with malignant pleural effusion

- Stage IV disease

- Recurrent disease

- Squamous cell histology allowed

- Not eligible for curative treatment or treatment with bevacizumab

- Measurable disease according to RECIST

- Tumor (paraffin blocks or slides) must be available for correlative biomarker studies

- No uncontrolled brain metastases (or leptomeningeal disease)

- Controlled brain metastases allowed

- Able to receive appropriate therapeutic radiotherapy

- Able to taper off all steroids without symptoms suggestive of increased
intracranial pressure (nausea, vomiting, focal neurologic symptoms) for at
least 7 days

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- ANC ≥ 1.5 x 10^9/L

- Platelets ≥ 100 x 10^9/L

- Hemoglobin ≥ 9.0 g/L

- Total bilirubin ≤ 1.5 mg/dL

- AST and ALT < 2.5 times upper limit of normal

- Creatinine ≤ 1.5 mg/dL OR creatinine clearance > 50 mg/mL

- No known HIV or hepatitis B or C

- Not pregnant

- Negative pregnancy test

- Thrombotic or embolic event within the past 6 months allowed, provided adequately
controlled with therapeutic anticoagulation

- Hemoptysis allowed, provided it is not life threatening or requires palliative
procedures (e.g., endobronchial therapy or radiotherapy)

- No cardiac disease, including any of the following:

- NYHA class III-IV congestive heart failure

- Unstable angina (angina symptoms at rest)

- New onset angina (began within the past 3 months)

- Myocardial infarction within the past 6 months

- No uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg or
diastolic BP > 90 mm Hg despite optimal medical management

- No peripheral neuropathy ≥ grade 2

- No active clinically serious infection > CTCAE grade 2

- No serious non-healing wound, ulcer, or bone fracture

- No significant traumatic injury within the past 4 weeks

- No evidence or history of bleeding diathesis or coagulopathy

- No prior malignancy, except for adequately treated basal cell skin cancer, carcinoma
in situ of the cervix, or other cancer for which the patient has been disease-free
for 2 years

- Stage I (T1c) prostate cancer adequately treated 2 years prior to diagnosis of
NSCLC allowed, however metastatic prostate cancer currently receiving hormonal
therapy or chemotherapy is not allowed

- No significant psychiatric illness, in the opinion of the principal investigator,
that would prevent adequate informed consent or render therapy unsafe

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Concurrent therapeutic anticoagulation, > 325 mg acetylsalicylic acid, or chronic
non-steroid anti-inflammatory drug use allowed

- At least 14 days since prior and no concurrent radiotherapy

- More than 4 weeks since prior major surgery or open biopsy