Gefitinib in Treating Patients With Malignant Mesothelioma

Study Overview
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Brief Summary
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Phase II trial to study the effectiveness of gefitinib in treating patients who have malignant mesothelioma. Biological therapies such as gefitinib may interfere with the growth of the tumor cells and slow the growth of malignant mesothelioma

Detailed Description
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OBJECTIVES: I. Determine the activity of gefitinib, in terms of failure-free survival, in patients with malignant mesothelioma. II. Determine the response rate in patients treated with this drug. III. Determine the toxicity of this drug in these patients. IV. Determine the overall survival of patients treated with this drug. V. Determine whether overexpression of epidermal growth factor receptor and expression of cyclo-oxygenase-2 can predict the effectiveness of this drug in these patients. OUTLINE: This is a multicenter study. Patients receive oral gefitinib once daily on days 1-21. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months for 1 year and then every 6 months for up to 3 years. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 7-10 months.

Official Title
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A Phase II Study Of ZD 1839 (NSC 715055, IND 61187) In Patients With Malignant Mesothelioma

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

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed malignant mesothelioma that is not amenable to curative surgery or radiotherapy Epithelial, sarcomatoid, or mixed subtype Any site of origin (including, but not limited to, the pleura, peritoneum, pericardium, or tunica vaginalis) allowed Measurable disease, defined as lesions that can be accurately measured in at least 1 dimension (longest diameter) as at least 20 mm with conventional techniques or at least 10 mm with spiral CT scan Must be outside prior radiation port Lesions not considered measurable include the following: Bone lesions Leptomeningeal disease Ascites Pleural/pericardial effusion Inflammatory breast disease Lymphangitis cutis/pulmonis Abdominal masses not confirmed and followed by imaging techniques Cystic lesions No known brain metastases Performance status - CTC 0-1 Granulocyte 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 no greater than 2.5 times ULN Creatinine no greater than 1.5 times ULN No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Not pregnant or nursing Fertile patients must use effective contraception No other concurrent active malignancy except nonmelanoma skin cancer Disease considered not currently active if completely treated with less than a 30% risk for relapse No other concurrent uncontrolled illness No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance No prior epidermal growth factor receptor-inhibitor therapy Prior intrapleural cytotoxic or sclerosing agents (including bleomycin) allowed No prior systemic cytotoxic chemotherapy for malignant mesothelioma No concurrent chemotherapy At least 1 week since prior CYP3A4 inducers (e.g., dexamethasone, glucocorticoids, progesterone) No concurrent CYP3A4 inducers (e.g., dexamethasone) No concurrent hormonal therapy (e.g., tamoxifen) except steroids for adrenal failure or hormones for non disease-related conditions (e.g., insulin for diabetes) See Disease Characteristics At least 4 weeks since prior radiotherapy No concurrent radiotherapy, including for palliation See Disease Characteristics At least 2 weeks since prior major surgery At least 1 week since other prior CYP3A4 inducers (e.g., carbamazepine, ethosuximide, griseofulvin, nafcillin, nelfinavir mesylate, nevirapine, oxcarbazepine, phenobarbital, phenylbutazone, phenytoin, primidone, rifabutin, rifampin, rofecoxib, St. John's Wort, sulfadimidine, sulfinpyrazone, or troglitazone) No other concurrent CYP3A4 inducers No concurrent CYP3A4 substrates or inhibitors No other concurrent investigational agent No concurrent combination antiretroviral therapy for HIV-positive patients No concurrent chlorpromazine, amiodarone, or chloroquine

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: Treatment (gefitinib)<br>Patients receive oral gefitinib once daily on days 1-21. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. | Drug: gefitinib<br>* Given orally<br>* Other names: ZD 1839;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 |
| --- | --- | --- |
| Percentage of patients who remain failure-free | Kaplan-Meier's product limit estimator and curves will be used. | Time between the initiation of treatment and initial failure (disease progression, relapse, death), assessed up to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response rate | An exact binomial confidence interval will be generated. | Up to 4 years | 
| Toxicities, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 | For each type of toxicity experienced, the frequency of reported toxicity will be summarized by the most severe grade. | Up to 4 years | 
| Overall survival | Kaplan-Meier's product limit estimator and curves will be used. | Up to 4 years | 
| Failure-free survival within patient subgroups defined in terms of epidermal growth factor receptor (EGFR) overexpression and cyclooxygenase-2 (COX-2) expression | An exact binomial confidence interval will be generated. | Up to 4 years |