Gefitinib and Everolimus in Treating Patients With Stage IIIB or Stage IV or Recurrent Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Gefitinib and everolimus may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Giving gefitinib together with everolimus may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects, best way to give, and best dose of giving gefitinib with everolimus and to see how well it works in treating patients with stage IIIB or stage IV or recurrent non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose of everolimus when administered with gefitinib in patients with stage IIIB or IV or recurrent non-small cell lung cancer. (Phase I) Determine the efficacy of this regimen in these patients. (Phase II) Secondary Assess the pharmacokinetics of everolimus, alone and in combination with gefitinib, in these patients. (Phase I) OUTLINE: This is an open-label, phase I, dose-escalation study of everolimus followed by a phase II study. Phase I: Patients receive oral everolimus once on day 1. Beginning on day 8, patients receive oral gefitinib once daily. Beginning on day 22, patients receive oral everolimus once daily. Both drugs are then given concurrently for the rest of the treatment. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of everolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 6 patients experiences dose-limiting toxicity. Phase II: Patients receive oral everolimus at the MTD determined in phase I and oral gefitinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Official Title
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A Phase I/II Trial of Fixed Doses of Daily Gefitinib With Escalating Doses of Daily RAD001 in Advanced Non-Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: everolimus
* Drug: gefitinib


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed non-small cell lung cancer (NSCLC) meeting 1 of the following stage criteria: Stage IIIB (unresectable, with malignant pleural or pericardial effusion) Stage IV disease Recurrent disease Measurable or evaluable indicator lesions Progressive disease after receiving ≥ 1 prior chemotherapy regimen that included cisplatin or carboplatin and docetaxel No uncontrolled brain or leptomeningeal metastases Must not require concurrent glucocorticoids for control of metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 70-100% OR ECOG 0-2 Life expectancy Not specified Hematopoietic WBC ≥ 3,000/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 9.0 g/dL Hepatic Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST ≤ 2.5 times ULN Renal Creatinine ≤ 1.5 times ULN OR Creatinine clearance ≥ 60 mL/min Cardiovascular No congestive heart failure No New York Heart Association class III or IV heart disease No unstable angina Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No severe infection No severe malnutrition No other serious medical illness No other malignancy within the past 3 years except adequately treated basal cell or squamous cell skin cancer or carcinoma of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent biologic therapy No concurrent immunotherapy Chemotherapy See Disease Characteristics No prior conventional chemotherapy for metastatic or recurrent NSCLC (phase II only) At least 4 weeks since prior chemotherapy No other concurrent chemotherapy Endocrine therapy See Disease Characteristics No concurrent oral steroids for management of skin toxicity Radiotherapy At least 4 weeks since prior radiotherapy No concurrent radiotherapy Surgery At least 4 weeks since prior major surgery No concurrent surgery for an identifiable lesion Other Recovered from all prior therapy No prior gefitinib, erlotinib, or other epidermal growth factor tyrosine kinase inhibitor No concurrent cytotoxic therapy (e.g., methotrexate for rheumatoid arthritis) No other concurrent oncolytic agents

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Gefitinib and Everolimus (RAD001)<br>Phase I: Patients receive oral everolimus once on day 1. Beginning on day 8, patients receive oral gefitinib once daily. Beginning on day 22, patients receive oral everolimus once daily. Both drugs are then given concurrently for the rest of the treatment. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of everolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 6 patients experiences dose-limiting toxicity. Phase II: Patients receive oral everolimus at the MTD determined in phase I and oral gefitinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. | Drug: everolimus<br> <br> Drug: gefitinib<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Objective Response | Determine efficacy of the combination oral daily gefitinib and oral daily RAD001 in patients with advanced NSCLC. Response and progression will be evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST). | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer