Erlotinib in Treating Patients With Malignant Mesothelioma of the Lung

Study Overview
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Brief Summary
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Erlotinib may interfere with the growth of tumor cells and slow the growth of the tumor. This phase II trial is studying how well erlotinib works in treating patients with malignant mesothelioma of the lung

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the 1-year survival rate in patients with unresectable malignant pleural mesothelioma treated with erlotinib. II. Determine the response rate in patients with measurable disease treated with this drug. III. Determine the frequency and severity of toxic effects of this drug in these patients. IV. Measure epidermal growth factor receptor (EGFR) expression, EGFR gene amplification, and other activation products in the EGFR signaling pathway in tumor samples and correlate with clinical outcomes in patients treated with this drug. OUTLINE: This is a multicenter study. Patients receive oral erlotinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 6 months for 2 years and then annually for 1 year. PROJECTED ACCRUAL: A total of 55 patients will be accrued for this study within 14-18 months.

Official Title
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A Phase II Study of Oral EGFR Tyrosine Kinase Inhibitor OSI-774 (NSC-718781) in Patients With Malignant Pleural Mesothelioma

Conditions
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Advanced Malignant Mesothelioma, Epithelial Mesothelioma, Recurrent Malignant Mesothelioma, Sarcomatous Mesothelioma

Intervention / Treatment
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* Drug: erlotinib hydrochloride
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed malignant pleural mesothelioma Epithelial Sarcomatous Biphasic Measurable or nonmeasurable disease Not amenable to extrapleural pneumonectomy No known CNS metastases Performance status - Zubrod 0-1 WBC at least 3,000/mm^3 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT or SGPT no greater than 1.5 times ULN (5 times ULN if liver involvement of tumor) Creatinine no greater than 2 times ULN No gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation No active peptic ulcer disease No intractable nausea or vomiting Must be able to swallow and/or receive enteral medications via gastrostomy feeding tube No known history of the following: Dry eye syndrome Sjogren's syndrome Keratoconjunctivitis sicca Exposure keratopathy Fuch's dystrophy Other active disorders of the cornea Not pregnant or nursing Fertile patients must use effective contraception No HIV-positive patients receiving combination antiretroviral therapy No other prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or stage I or II cancer that is in complete remission No prior biologic therapy for this tumor No prior chemotherapy for this tumor See Disease Characteristics At least 3 weeks since prior radiotherapy and recovered See Disease Characteristics At least 4 weeks since prior major surgery (e.g., thoracotomy or laparotomy), excluding minor surgeries (e.g., mediastinoscopy, thoracoscopy, or minor biopsies) Recovered from prior surgery No prior surgical procedures affecting absorption No prior investigational anticancer agents for this tumor
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: Treatment (erlotinib hydrochloride)<br>Patients receive oral erlotinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: erlotinib hydrochloride<br>* Given orally<br>* Other names: OSI-774;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 |
| --- | --- | --- |
| Overall survival rate | Erlotinib hydrochloride will not be of further interest if the true one-year survival rate is 35% or less, but of considerable interest if 55% or more. | 1 year | 
| RECIST response rate |  | Up to 3 years | 
| Association between EGFR expression with survival and response |  | Up to 3 years |