Safety and Tolerability Study of ISIS EIF4E Rx in Combination With Carboplatin and Paclitaxel

Inclusion Criteria

• •Male or female patients age \>/= 18 years
• •Histologically or cytologically confirmed diagnosis of NSCLC
• •Stage IV disease (including patients with pleural effusion who were previously classified as Stage IIIB)
• •All of the following if patient has had prior radiation therapy:
• •1. Lesion(s) used for determination of response were not previously irradiated or have increased in size since the completion of radiotherapy
• •2. The patient has recovered from any acute effects of the radiotherapy
• •3. Radiotherapy was completed at least 4 weeks prior to Screening
• •Part 1: Have at least non-measurable evaluable disease (e.g., lesions which are smaller than the minimum size required for measurability; other non-measurable lesions such as bone metastases, malignant pleural effusion)
• •Part 2: Have measurable disease, defined as at least 1 lesion that can be accurately measured in at least 1 dimension
• •Performance status of 0 or 1 on the ECOG Performance Status Scale
• •Have an estimated life expectancy of at least 12 weeks
• •Adequate organ function within 14 days prior to first study dose (ISIS EIF4E Rx or carboplatin/paclitaxel, whichever occurs first) as defined by:
• •1. Absolute neutrophil count (ANC) \>/= 1.5 x 109/L
• •2. Platelet count \>/= 100 x 109/L
• •3. Hemoglobin \>/=9 g/dL (\>/= 5.6 mmol/L). Patients may receive packed RBC transfusion to achieve this level at the discretion of the investigator.
• •4. Total bilirubin \< 1.5 x upper limit of normal (ULN) unless elevated secondary to conditions such as Gilbert's Disease
• •5. Aspartate aminotransferase (AST) \< 3 x ULN (\< 5 x ULN in the presence of hepatic metastases)
• •6. Alanine aminotransferase (ALT) \< 3 x ULN (\< 5 x ULN in the presence of hepatic metastases)
• •7. Alkaline phosphatase \< 3.0 x ULN
• •8. Calculated creatinine clearance \>/= 60 mL/min per Cockcroft and Gault formula
• •Satisfy one of the following:
• •1. Females: non-pregnant and non-lactating; surgically sterile, post-menopausal, or patient or partner compliant with a reliable contraceptive regimen, as determined by Investigator, for 4 weeks prior to Screening. Patients of reproductive potential must test negative for pregnancy at Screen and must agree to use a reliable method of birth control during the study and for the 10 weeks following the last dose of ISIS EIF4E Rx.
• •2. Males: surgically sterile or patient or partner must agree to use a reliable contraceptive method, as determined by the Investigator during the study and for the 10 weeks following the last dose of ISIS EIF4E Rx.
• •For Part 1: have discontinued all prior chemotherapies, biological therapies, and other investigational therapies for cancer for at least 4 weeks (6 weeks for mitomycin-C or nitrosoureas) prior to study treatment and recovered from the acute effects of therapy.