CCI-779 in Treating Patients With Stage IIIB (With Pleural Effusion) or Stage IV Non-Small Cell Lung Cancer

OBJECTIVES: Primary I. Determine the response rate in patients with stage IIIB (with pleural effusion) or IV non-small cell lung cancer treated with CCI-779.

II. Determine the clinical toxic effects of this drug in these patients.

Secondary I. Determine the 24-week progression-free survival rate in patients treated with this drug.

II. Determine the time to progression and overall survival of patients treated with this drug.

III. Evaluate predictive markers of activity (e.g., PTEN mutations and phosphoAkt expression) of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 6 months for up to 5 years.

PROJECTED ACCRUAL: A total of 25-55 patients will be accrued for this study within 12 months.

Inclusion criteria

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

• Stage IIIB (with pleural effusion) or IV disease
• Measurable disease

• At least 1 lesion ≥ 2.0 cm by conventional techniques OR ≥ 1.0 cm by spiral CT scan
• The following are not considered measurable disease:

• Bone lesions
• Leptomeningeal disease
• Ascites
• Pleural/pericardial effusion
• Inflammatory breast disease
• Lymphangitis cutis/pulmonis
• Cystic lesions
• Abdominal masses that are not confirmed and followed by imaging techniques
• Blood and tissue blocks available
• Must have accessible tumor (i.e., superficial lesions such as lymph node, subcutaneous nodules) to provide core needle biopsy tissue before and during study treatment
• No known brain metastases
• Performance status - ECOG 0-2
• At least 12 weeks
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL
• Bilirubin ≤ 2 times upper limit of normal (ULN)
• AST ≤ 3 times ULN (5 times ULN if hepatic metastases are present)
• Creatinine ≤ 1.5 times ULN
• Serum fasting cholesterol ≤ 350 mg/dL
• Serum fasting triglycerides ≤ 400 mg/dL
• HIV negative
• No uncontrolled infection
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or non-invasive carcinomas
• No concurrent severe underlying disease that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study treatment
• No prior biologic therapy
• No prior gene therapy
• No prior immunotherapy
• No concurrent immunotherapy
• No concurrent prophylactic growth factors to support neutrophil count
• No prior chemotherapy for NSCLC except low-dose cisplatin as a radiosensitizer
• No other concurrent chemotherapy
• No concurrent dexamethasone (10 mg IV)
• No prior radiotherapy to 30% or more of bone marrow
• Concurrent radiotherapy for underlying malignancy and non-target sites (e.g., painful pre-existing bony metastasis) allowed
• No other concurrent investigational therapy
• No concurrent immunosuppressive therapy