Bortezomib in Treating Patients With Malignant Pleural 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. PURPOSE: This phase II trial is studying the side effects of bortezomib and how well it works in treating patients with malignant pleural mesothelioma.

Detailed Description
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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.

Official Title
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An Open Label Phase II Multicentre Clinical Trial of Single Agent Bortezomib in Patients With Malignant Pleural Mesothelioma

Conditions
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Malignant Mesothelioma

Intervention / Treatment
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* Drug: bortezomib
* Procedure: quality-of-life assessment


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bortezomib 1.6mg/m2<br> | Drug: bortezomib<br> <br> Procedure: quality-of-life assessment<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective tumor response rate (complete response or partial response) as assessed by modified RECIST criteria | The objective tumour response rate is a primary endpoint of the study. This will be a proportion of evaluable subjects who achieve a confirmed CR or PR per modified RECIST guidelines within four cycles (20 weeks) of treatment. | 28 days prior to baseline, at 10 weeks and at end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to disease progression |  | Time to disease progression is measured from first treatment until the date of PD or death whichever is first reported. Subjects who did not progress or die will be censored at the day of their last tumour assessment. | 
| Overall survival |  | Overall Survival is measured from the date of first treatment to the date of the subject's death. If the subject is alive or the vital status is unknown, the date of death will be censored at the date that the subject is last known to be alive. | 
| Safety |  | The assessment of safety will be based mainly on the frequency of adverse events and on the number of laboratory values that fall outside of the pre-determined normal ranges. | 
| Quality of life | Quality of life will be assessed using the Lung Cancer Symptom Score | Week 1, Week 10 and end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent malignant mesothelioma, stage IA malignant mesothelioma, stage IB malignant mesothelioma, stage II malignant mesothelioma, stage III malignant mesothelioma, stage IV malignant mesothelioma