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

Study Overview
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Brief Summary
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This phase II trial is studying how well CCI-779 works in treating patients with stage IIIB non small cell lung cancer (with pleural effusion) or stage IV non-small cell lung cancer. Drugs used in chemotherapy, such as CCI-779, work in different ways to stop tumor cells from dividing so they stop growing or die. CCI-779 may also stop the growth of tumor cells by blocking the enzymes necessary for their growth.

Detailed Description
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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.

Official Title
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A Phase II Study of the mTOR Inhibitor, CCI-779 in Patients With Advanced Non-Small Cell Lung Cancer

Conditions
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Recurrent Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: temsirolimus
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. | Drug: temsirolimus<br>* Given IV<br>* Other names: Torisel;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed tumor response according to the Response Evaluation Criteria in Solid Tumors (RECIST) | Confidence intervals for the true success proportion will be calculated using the Duffy-Santner approach. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Computed and binomial confidence intervals for the true success proportion will be calculated. | 24 weeks | 
| Survival time | Estimated using the method of Kaplan-Meier. | Time from registration to death due to any cause, assessed up to 5 years | 
| Time to disease progression | Estimated using the method of Kaplan-Meier. | Time from registration to documentation of disease progression, assessed up to 5 years | 
| Effects of CCI-779 on mTOR as assessed by expression of 4EBP, phosphoAkt, p70S6kinase, eIF4E, cyclinD1, Her2, and EGFR |  | Day 8 |