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

Inclusion 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