Bortezomib in Treating Patients With Malignant Pleural Mesothelioma

Malignant Mesothelioma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00513877
• Other study ID #: 05-10 ICORG
• Secondary ID: ICORG-05-10EUDRA
• Status: Completed
• Phase: Phase 2
• First received: August 8, 2007
• Last updated: December 30, 2014
• Start date: May 2006

Study information

• Verified date: January 2013
• Source: ICORG- All Ireland Cooperative Oncology Research Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Ireland: Irish Medicines Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lung Neoplasms
• Malignant Mesothelioma
• Mesothelioma

Intervention

Drug:
• bortezomib

Procedure:
• quality-of-life assessment

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Gent	Ghent
Ireland	Cork University Hospital	Cork
Ireland	Adelaide and Meath Hospital, Dublin Incorporating the National Children's Hospital	Dublin
Ireland	Beaumont Hospital	Dublin
Ireland	Mater Misericordiae University Hospital	Dublin
Ireland	St. James's Hospital	Dublin
Ireland	St. Vincent's University Hospital	Dublin
Ireland	Galway University Hospital	Galway
Netherlands	Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital	Amsterdam
United Kingdom	Centre for Cancer Research and Cell Biology at Queen's University Belfast	Belfast	Northern Ireland
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow	Scotland
United Kingdom	Saint Bartholomew's Hospital	London	England
United Kingdom	Royal Marsden - Surrey	Sutton	England

Sponsors (1)

Lead Sponsor	Collaborator
ICORG- All Ireland Cooperative Oncology Research Group

Countries where clinical trial is conducted

Belgium,  Ireland,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	Yes
Secondary	Quality of life	Quality of life will be assessed using the Lung Cancer Symptom Score	Week 1, Week 10 and end of treatment	No