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

Study Overview
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Brief Summary
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RATIONALE: Bortezomib 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. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with cisplatin may kill more tumor cells. PURPOSE: This phase II trial is studying the side effects and how well giving bortezomib together with cisplatin works as first-line therapy in treating patients with malignant mesothelioma.

Detailed Description
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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.

Official Title
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Phase II Study of Bortezomib (VELCADE) With Cisplatin as First Line Treatment of Malignant Mesothelioma

Conditions
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Malignant Mesothelioma

Intervention / Treatment
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* Drug: bortezomib
* Drug: cisplatin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: bortezomib|nan|
|Drug: cisplatin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) rate at 18 weeks |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall objective response rate |  |  | 
| Symptomatic response rate |  |  | 
| Safety as measured by NCI CTCAE v3.0 and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity questionnaire |  |  | 
| Duration of PFS |  |  | 
| Overall survival |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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localized malignant mesothelioma, recurrent malignant mesothelioma, advanced malignant mesothelioma