Primary Outcome Measures:
- Objective tumor response rate (complete response or partial response) as assessed by modified RECIST criteria [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Time to disease progression [ Designated as safety issue: No ]
- Overall survival [ Designated as safety issue: No ]
- Safety [ Designated as safety issue: Yes ]
- Quality of life [ Designated as safety issue: No ]
Detailed Description:
Objectives:
- Primary
-
- Assess the clinical efficacy of bortezomib based on the evaluation of objective tumor response rate.
- Secondary
-
- Assess additional clinical efficacy of bortezomib based on the evaluation of time to early disease progression and median overall 2-year survival rate.
- Assess safety and toxicity in these patients.
- Assess quality of life using the Lung Cancer Symptom Score.
Outline: This is a multicenter study. Patients are stratified according to current treatment (first-line vs second-line)
Patients receive bortezomib IV on days 1, 8, 15, and 22. Treatment repeats every 5 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients exhibiting objective response or stable disease by week 20, may continue treatment at the discretion of the investigator until evidence of disease progression.
Quality of life is assessed periodically.
After completion of study treatment, patients are followed for up to 2 years.
Projected Accrual: 57 first-line setting and 54 second-line setting patients will be accrued for this study.
Criteria
Disease Characteristics:
- Inclusion criteria:
-
- Histologically confirmed malignant pleural mesothelioma
- Meets 1 of the following criteria for first-line or second-line chemotherapy:
- Patients in the first-line setting must be unsuitable for, cannot access locally, or refuse combination chemotherapy
- Patients in the second-line setting must be unsuitable for, cannot access locally, or refuse cytotoxic chemotherapy after failure of a first-line regimen
- Second-line patients may not have received more than 1 prior line of antineoplastic treatment for this cancer
- Pleural effusions should be drained before treatment whenever possible
- Talc or tetracycline pleurodesis may be used per standard practice for uncontrollable pleural effusions (recurrent despite regular drainage)
- Exclusion criteria:
-
- Symptomatic or known brain or leptomeningeal metastases
Patient Characteristics:
- Inclusion criteria:
-
- ECOG performance status 0-2
- Hemoglobin ≥ 10 g/dL
- Neutrophil count ≥ 1,500 mm^3
- Platelet count ≥ 100,000/mm^3
- Creatinine clearance ≥ 30 mL/min
- AST and ALT < 3 times upper limit of normal
- Fertile patients must use effective contraception during study therapy
- Exclusion criteria:
-
- Pregnant or breastfeeding
- History of prior malignant tumor within the past 3 years except for nonmelanoma skin tumor or carcinoma in situ of the cervix
- Patients suitably fit to receive a platinum doublet based chemotherapy (first-line only)
- Uncontrolled or severe cardiovascular disease including any of the following:
- Myocardial infarction within the past 6 months
- New York Heart Association class III or IV heart failure
- Uncontrolled angina
- Clinically significant pericardial disease
- Cardiac amyloidosis
- Neuropathy ≥ grade 2 OR grade 1 with pain
- Serious medical (e.g., uncontrolled diabetes, hepatic disease, or infection) or psychiatric illness that would interfere with study participation
- Patients with known HIV or hepatitis B or C infection
Prior Concurrent Therapy:
- No prior bortezomib
- No prior extensive radiation therapy, systemic chemotherapy, or other antineoplastic therapy within 4 weeks before enrollment
- No preplanned surgery or procedures that would interfere with the study
- More than 4 weeks since enrollment in another therapeutic clinical trial (i.e., received an experimental drug or used an experimental medical device)
- Concurrent participation in non-treatment studies is allowed provided they do not interfere with participation in this study
- No concurrent experimental or antineoplastic agent other than bortezomib
- Medications that may have antineoplastic activity, but are taken for other reasons than specific antineoplastic effect (e.g., megestrol [Megace®], cyclo-oxygenase-2 [COX-2] inhibitors, or bisphosphonates) are allowed
