The Online Asbestos, Asbestos Cancer, & Mesothelioma Authority

Clinical Trials

Primary Outcome Measures:

• Response rate (complete and partial response) [ Designated as safety issue: No ]
  

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

advanced malignant mesothelioma epithelial mesothelioma recurrent malignant mesothelioma sarcomatous mesothelioma

Mesothelioma Sorafenib Adenoma Recurrence Neoplasms, Glandular and Epithelial

Neoplasms Neoplasms by Histologic Type Mesothelioma Molecular Mechanisms of Pharmacological Action Antineoplastic Agents

Neoplasms, Mesothelial Therapeutic Uses Enzyme Inhibitors Protein Kinase Inhibitors Pharmacologic Actions