Bortezomib in Treating Patients With Malignant Pleural Mesothelioma

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...

Date First Received: August 8, 2007

Last Updated: March 18, 2008

Verified by: National Cancer Institute (NCI), August 2007

Clinical Trial Phase: Phase 2 | Start Date: May 2006

Overall Status: Recruiting

Estimated Enrollment: 111

Brief Summary

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

Condition Keyword(s):

• Malignant Mesothelioma

Intervention(s):

• Drug: bortezomib
• Procedure: enzyme inhibitor therapy
• Procedure: quality-of-life assessment

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.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label

Detailed Clinical Trial 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.

Outcome Measures for this Clinical Trial

Primary:

• Objective tumor response rate (complete response or partial response) as assessed by modified RECIST criteria

Secondary:

• Time to disease progression
• Overall survival
• Safety
• Quality of life

Criteria for Participation in this Clinical Trial

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 <>
• 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

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Irish Clinical Oncology Research Group

Universitair Ziekenhuis Gent

Ghent B-9000 Belgium

Adelaide and Meath Hospital, Dublin Incorporating the National Children's Hospital

Dublin 24 Ireland

Beaumont Hospital

Dublin 9 Ireland

Cork University Hospital

Cork Ireland

Galway University Hospital

Galway Ireland

Mater Misericordiae University Hospital

Dublin 7 Ireland

St. James's Hospital

Dublin 8 Ireland

St. Vincent's University Hospital

Dublin 4 Ireland

Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital

Amsterdam 1066 CX Netherlands

Royal Marsden - Surrey

Sutton England SM2 5PT United Kingdom

Saint Bartholomew's Hospital

London England EC1A 7BE United Kingdom

Centre for Cancer Research and Cell Biology at Queen's University Belfast

Belfast Northern Ireland BT9 7BL United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow Scotland G11 6NT United Kingdom

Overall Clinical Trial Officials and Contacts

Dean A. Fennell, MD, PhD Principal Investigator Centre for Cancer Research and Cell Biology at Queen's University Belfast

Additional Information

Information obtained from ClinicalTrials.gov on April 01, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00513877

Study ID Number: CDR0000560151

ClinicalTrials.gov Identifier: NCT00513877

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial