Bortezomib and Cisplatin as First-Line Therapy in Treating Patients With Malignant Mesothelioma

OBJECTIVES:

• Determine the activity and safety of bortezomib and cisplatin as first-line treatment in patients with malignant mesothelioma.
• Validate the use of progression-free survival rate as a primary endpoint for the design of phase II mesothelioma trials.

OUTLINE: This is a nonrandomized, open-label, multicenter study.

Patients receive cisplatin IV over 1 hour on day 1 and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed periodically.

PROJECTED ACCRUAL: A total of 76 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed pleural malignant mesothelioma, meeting 1 of the following criteria:

• Recurrent disease after radical surgery
• Disease not considered suitable for radical treatment
• Measurable or evaluable disease
• No clinical evidence of brain or leptomeningeal metastases

PATIENT CHARACTERISTICS:

• WHO performance status 0-1
• Life expectancy > 12 weeks
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Absolute neutrophil count > 1,500/mm³
• Platelet count > 100,000/mm³
• Creatinine clearance > 60 mL/min OR > 50 mL/min
• ALT and AST < 2.5 times upper limit of normal (ULN) (< 5 times ULN if liver metastases present)
• Bilirubin < 1.5 times ULN
• No concurrent secondary malignancy except carcinoma in situ of the cervix or adequately treated basal cell skin cancer
• No other malignancy treated within the past 5 years

• Melanoma, breast cancer, or hypernephroma treated within the past 5 years and without recurrence are allowed
• No uncontrolled or severe cardiovascular disease, including any of the following:

• Myocardial infarction within the past 6 months
• New York Heart Association class III-IV heart failure
• Uncontrolled angina
• Clinically significant pericardial disease or cardiac amyloidosis
• No infiltrative pulmonary or pericardial disease
• No preexisting peripheral neuropathy
• No known or suspected allergy or intolerance to boron, mannitol, or heparin, if an indwelling catheter is used
• No psychological, familial, sociological, or geographical condition that would preclude protocol compliance

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior systemic chemotherapy for mesothelioma
• No other concurrent antineoplastic agents except medications that may have antineoplastic activity but are taken for other reasons (e.g., megestrol acetate, cyclooxygenase-2 inhibitors, or bisphosphonates)
• No other concurrent experimental agents