A Phase 1-2 XIAP Antisense AEG35156 With Carboplatin and Paclitaxel in Patients With Advanced Non-Small Cell Lung Cancer

Inclusion Criteria:

• Patients with histologically or cytologically confirmed stage IIIB (malignant pleural effusion) or stage IV non small cell lung cancer who are candidates for carboplatin and paclitaxel chemotherapy for metastatic disease
• ECOG performance < 2
• One or more tumors measurable by RECIST criteria on CT scan or MRI (Phase 2 part only)
• Life expectancy of at least 3 months
• Age > 18 years
• Signed, written IRB-approved informed consent
• A negative serum pregnancy test (if applicable)
• Acceptable liver function:
• Bilirubin within normal limit
• AST (SGOT), ALT (SGPT) and Alkaline phosphatase < 2.0 times the institution's upper limit of normal
• Acceptable renal function:
• Serum creatinine within normal limits, OR calculated creatinine clearance > 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
• Acceptable hematologic status:
• Granulocyte > 1500 cells/uL
• Platelet count > 100,000 plt/uL
• Hemoglobin > 9.0 g/dL
• Acceptable coagulation status:
• PT within normal limits
• PTT within normal limits
• For women of child-bearing potential, the use of effective contraceptive methods during the study
• Prior radiotherapy is allowed provided disease progression outside the radiation field has been documented, treatment completed at least 2 weeks prior to registration and less than 25% of the bone marrow exposed

Exclusion Criteria:

• Prior chemotherapy for metastatic disease.
• Patients with prior history of peripheral neuropathy
• Patients with hypersensitivity to platinum containing compounds, mannitol or drugs formulated in Chremophor EL.
• Active progressive brain metastases including the presence of any related symptoms or need for corticosteroids. A CT or MRI scan of the head is necessary in patients with a history of brain metastases to document the stability of prior lesions.
• Known bleeding diathesis
• Pregnant or nursing women. NOTE: Women of child-bearing potential must agree to use adequate contraception (sterile or surgically sterile; hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Men who are unwilling to use acceptable forms of birth control when engaging in sexual contact with women of child bearing potential
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
• Known infection with HIV, hepatitis B, or hepatitis C
• Serious nonmalignant disease that could compromise protocol objectives in the opinion of the investigator and/or the sponsor
• Patients who have received any other investigational agent within the last 30 days. Subjects who have used a previous antisense oligonucleotide in the last 90 days will be excluded
• Unwillingness or inability to comply with procedures required in this protocol