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.

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