PTK787/ZK 222584 in Treating Patients With Unresectable Malignant Mesothelioma

Study Overview
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Brief Summary
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RATIONALE: PTK787/ZK 222584 may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. PURPOSE: Phase II trial to study the effectiveness of PTK787/ZK 222584 in treating patients with unresectable malignant mesothelioma.

Detailed Description
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OBJECTIVES: Determine the efficacy of PTK787/ZK 222584, in terms of 3-month progression-free survival, in patients with malignant mesothelioma. Determine the response rate in patients treated with this drug. Determine the toxicity of this drug in these patients. Determine the overall and failure-free survival of patients treated with this drug. Correlate pretreatment circulating serum levels of vascular endothelial growth factor (VEGF), platelet-derived growth factor, and VEGF mRNA isoforms with response in patients treated with this drug. OUTLINE: This is a multicenter study. Patients receive oral PTK787/ZK 222584 daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months for 1 year, every 4 months for 1 year, and then every 6 months for 1 year.

Official Title
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A Phase II Study of PTK787/ZK222584 (NSC#719335) in Patients With Unresectable Malignant Mesothelioma

Conditions
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Malignant Mesothelioma

Intervention / Treatment
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* Drug: PTK787/ZK 222584


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed malignant mesothelioma of 1 of the following types: Epithelial Sarcomatoid Mixed Not amenable to radiotherapy or curative surgery Any site of origin including, but not limited to, the following: Pleura Peritoneum Pericardium Tunica vaginalis At least one unidimensionally measurable lesion outside of prior irradiation port At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan The following are not considered measurable: Bone lesions Leptomeningeal disease Ascites Pleural/pericardial effusion Lymphangitis cutis/pulmonis Abdominal masses that are not confirmed and followed by imaging techniques Cystic lesions No known brain metastases PATIENT CHARACTERISTICS: Age Over 18 Performance status ECOG 0-1 Life expectancy Not specified Hematopoietic Granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic Bilirubin no greater than 1.5 times upper limit of normal (ULN) AST no greater than 2.5 times ULN Renal Creatinine no greater than 1.5 times ULN Negative for proteinuria by dipstick OR Urinary protein no greater than 500 mg and creatinine clearance at least 50 mL/min Cardiovascular No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective double-barrier contraception No currently active second malignancy except non-melanoma skin cancers (unless therapy is completed and risk of relapse is less than 30%) No other concurrent uncontrolled illness No ongoing active infections No psychiatric illness or social situation that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy No prior signal transduction inhibitor therapy No prior angiogenesis inhibitor therapy Chemotherapy No prior cytotoxic chemotherapy for this malignancy No concurrent chemotherapeutic agents Prior intrapleural cytotoxic or sclerosing therapy (including bleomycin) allowed Endocrine therapy No concurrent hormonal therapy except steroids for adrenal failure or hormones for non-disease-related conditions (e.g., insulin for diabetes) Radiotherapy See Disease Characteristics At least 4 weeks since prior radiotherapy No concurrent palliative radiotherapy Surgery See Disease Characteristics At least 2 weeks since prior major surgery Other At least 30 days since prior investigational agents At least 7 days since prior grapefruit or grapefruit juice At least 7 days since prior CYP3A4 inducers No prior PTK787/ZK 222584 No prior tyrosine kinase inhibitor therapy No other concurrent investigational agents No concurrent isoenzyme inducers or inhibitors of p450 No concurrent warfarin or similar oral anticoagulants Heparin allowed No concurrent grapefruit or grapefruit juice No concurrent combination antiretroviral therapy for HIV-positive patients

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: PTK787/ZK 222584<br>Patients receive oral PTK787/ZK 222584 daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months for 1 year, every 4 months for 1 year, and then every 6 months for 1 year. | Drug: PTK787/ZK 222584<br>* oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival |  | Up to 3 years post-treatment | 
| Failure free survival |  | Up to 3 years post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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advanced malignant mesothelioma, epithelial mesothelioma, recurrent malignant mesothelioma, sarcomatous mesothelioma