Phase I/II Study to Evaluate the Efficacy and Safety of Combination Chemotherapy With Carboplatin, Bortezomib and Bevacizumab as First Line Therapy in Patients With Advanced Non-small Cell Lung Cancer

Inclusion Criteria:

- Histologically confirmed SCLC (adeno- and large cell, anaplastic carcinoma and
broncho-alveolar-carcinoma). Patients with squamous-cell histology are eligible with
extra thoracic or peripheral lung lesions only.

- Sputum cytology alone not acceptable evidence of cell type. Cytologic specimens
obtained by brushing, washings, or needle aspiration of defined lesions will be
acceptable. Mixed tumors will be categorized by the predominant cell type unless a
small cell anaplastic elements are present, in which case the patient is ineligible.

- Stage III B because of pleural effusion or Stage IV disease

- Measurable disease.

- Age: 18 years or older

- No history of thrombotic, hemorrhagic, or coagulopathy disorders

- INR<1.5 and a PTT no greater than normal limits of normal within 1 week prior to
registration. NB: subjects with lung cancer placed on anticoagulant therapy for a
thrombotic event are not eligible for this study.

- No gross hemoptysis (defined as bright red blood of ½ teaspoon or more)

- No CNS or brain metastasis

- Laboratory Criteria (completed <2 weeks before enrollment):

- Hematologic: WBC > 3500/mm3 or ANC > 1500/mm3 and platelet count > 100 000/
mm3;

- Hepatic: Total bilirubin < 1.5 mg/dl

- Renal: Creatinine < 1.5 mg/dl. or calculated

- Creatinine clearance > 45 ml/min (NB: Urine protein:creatinine ratio in
exclusion criteria)

- ECOG performance status < 2

- Be free of active infection.

- Be available for active follow up.

- No prior chemotherapy for metastatic disease.

- Be disease free for > 5 years if they had a prior second malignancy other than
treated basal cell carcinoma or squamous cell skin cancer, or carcinoma in situ of
the cervix.

- Female subject post-menopausal; surgically sterilized or willing to use an acceptable
method of birth control for the duration of the study. Male subject agrees to use an
acceptable method for contraception for the duration of the study.

Exclusion Criteria:

- CNS or brain metastasis

- Patient has = or greater Grade 2 peripheral neuropathy within 14 days before
enrollment.

- Known previous sensitivity reactions with boron, or mannitol,

- Patients with known HIV positivity

- Myocardial infarction within 6 months prior to enrollment or has New York Hospital
Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe
uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
ischemia or active conduction system abnormalities. Any ECG abnormality at Screening
has to be documented by the investigator as not medically relevant.

- Blood pressure of >150/100 mmHG

- History of myocardial infarction or stroke within 6 months

- Clinically significant peripheral vascular disease

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 0, anticipation of need for major surgical procedure during the course
of the study.

- Minor surgical procedure such as fine needle aspirations or core biopsies within 7
days prior to day 0

- Urine protein: Creatinine ratio > 1.0 at screening

- History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess
within 6 months prior to Day 0

- Serious, non-healing wound, ulcer, or bone fracture

- Lung carcinoma or any histology in close proximity to a major vessel or cavitation

- Female subject is pregnant or breast-feeding. Confirmation that the subject is not
pregnant. Pregnancy testing is not required for post-menopausal or surgically
sterilized women.

- Patient has received other investigational drugs with 14 days before enrollment or is
expected to participate in an experiment drug study during this study treatment.

- Serious medical or psychiatric illness likely to interfere with participation in this
clinical study.