ptk787/zk 222584 in treating patients with unresectable malignant mesothelioma

Conditions: Malignant Mesothelioma

Summary: 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.

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.

Eligibility criteria:
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

Keywords: advanced malignant mesothelioma epithelial mesothelioma recurrent malignant mesothelioma sarcomatous mesothelioma