Sorafenib in Treating Patients With Malignant Mesothelioma

RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well sorafenib works in treating patients with malignant mesothelioma.

OBJECTIVES:

Primary

• Determine the partial response and complete response rate in patients with malignant mesothelioma treated with sorafenib.

Secondary

• Determine the 3-month failure-free survival of patients treated with this drug.
• Determine the median and overall survival of patients treated with this drug.
• Determine the toxicity profile of this drug in these patients.
• Correlate the presence of mutations in exons 11 and 15 of the B-raf gene in tumor tissue with anti-tumor activity of this drug in these patients.
• Correlate the amount of phospho-ERK1/2 expression in pretreatment tumor tissue with anti-tumor activity of this drug in these patients.
• Correlate baseline levels of and changes in angiogenic cytokines (vascular endothelial growth factor and platelet-derived growth factor) with anti-tumor activity of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at least every 2 months for 1 year, every 4 months for 1 year, and then every 6 months for 1 year.

PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study within 6-8 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant mesothelioma

  • Epithelial, sarcomatoid, or mixed type
  • Any site of origin (e.g., pleura, peritoneum, pericardium, or tunica vaginalis)

• Measurable disease

  • At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan

    • Target lesion must be outside prior radiotherapy port
  • Patients with pleural rind only disease must have ≥ 1 level with 1 rind measuring ≥ 1.5 cm

  • The following are not considered measurable disease:

    • Bone lesions
    • Leptomeningeal disease
    • Ascites
    • Pleural or pericardial effusions
    • Lymphangitis cutis/pulmonis
    • Abdominal masses that are not confirmed and followed by imaging techniques
    • Cystic lesions
• Not amenable to curative surgery
• Must have tissue blocks or slides from a core surgical biopsy available
• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• No bleeding diathesis

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST ≤ 2.5 ULN
• INR < 1.5

Renal

• Creatinine ≤ 1.5 times ULN OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No hypertension

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No ongoing, active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other active malignancy except non-melanoma skin cancer, carcinoma in situ of the cervix, or any other completely treated malignancy that has< 30% chance of relapsing
• No history of allergic reactions attributed to compounds of similar chemical or biological composition to study drug
• No other uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior angiogenesis inhibitor therapy
• No concurrent prophylactic filgrastim (G-CSF), sargramostim (GM-CSF), or pegfilgrastim

Chemotherapy

• Prior intrapleural cytotoxic chemotherapy allowed*
• No more than 1 prior pemetrexed disodium-containing chemotherapy regimen (i.e., pemetrexed disodium alone or in combination with any other agent)
• At least 4 weeks since prior pemetrexed disodium-containing chemotherapy regimen
• No concurrent chemotherapy NOTE: *Not considered systemic chemotherapy

Endocrine therapy

• No concurrent hormonal therapy except hormones for non-disease-related conditions (e.g., insulin for diabetes) or steroids for adrenal failure

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy
• No concurrent palliative radiotherapy

Surgery

• At least 3 weeks since prior major surgery

Other

• No prior signal transduction inhibitor therapy
• No prior protein tyrosine kinase inhibitor therapy
• Prior intracavitary cytotoxic or sclerosing therapy (including bleomycin) allowed
• More than 28 days since prior and no other concurrent investigational agents

• No concurrent therapeutic anticoagulation therapy with warfarin or heparin derivatives

  • Concurrent prophylactic anticoagulation (e.g., low-dose warfarin) for venous or arterial access devices allowed provided that the requirements for INR are met
• No concurrent combination antiretroviral therapy for HIV-positive patients