PTK787/ZK 222584 in Treating Patients With Unresectable Malignant Mesothelioma

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