• Confirmed response [ Designated as safety issue: No ]
  

• Progression-free survival at 24 weeks [ Designated as safety issue: No ]
  
• Survival time [ Designated as safety issue: No ]
  
• Time to disease progression [ Designated as safety issue: No ]
  
• Effects of CCI-779 on mTOR [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the response rate in patients with stage IIIB (with pleural effusion) or IV non-small cell lung cancer treated with CCI-779.
• Determine the clinical toxic effects of this drug in these patients.

Secondary

• Determine the 24-week progression-free survival rate in patients treated with this drug.
• Determine the time to progression and overall survival of patients treated with this drug.
• 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.

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL

Hepatic

• Bilirubin ≤ 2 times upper limit of normal (ULN)
• AST ≤ 3 times ULN (5 times ULN if hepatic metastases are present)

Renal

• Creatinine ≤ 1.5 times ULN

Other

• 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior biologic therapy
• No prior gene therapy
• No prior immunotherapy
• No concurrent immunotherapy
• No concurrent prophylactic growth factors to support neutrophil count

Chemotherapy

• No prior chemotherapy for NSCLC except low-dose cisplatin as a radiosensitizer
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent dexamethasone (10 mg IV)

Radiotherapy

• 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

Surgery

• Not specified

Other

• No other concurrent investigational therapy
• No concurrent immunosuppressive therapy