Bortezomib in Treating Patients With Malignant Pleural Mesothelioma

December 30, 2014 updated by: Cancer Trials Ireland

An Open Label Phase II Multicentre Clinical Trial of Single Agent Bortezomib in 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

33

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Ghent, Belgium, B-9000
        • Universitair Ziekenhuis Gent
  • Ireland
      • Cork, Ireland
        • Cork University Hospital
      • Dublin, Ireland, 9
        • Beaumont Hospital
      • Dublin, Ireland, 7
        • Mater Misericordiae University Hospital
      • Dublin, Ireland, 4
        • St. Vincent's University Hospital
      • Dublin, Ireland, 24
        • Adelaide and Meath Hospital, Dublin Incorporating the National Children's Hospital
      • Dublin, Ireland, 8
        • St. James's Hospital
      • Galway, Ireland
        • Galway University Hospital
  • Netherlands
      • Amsterdam, Netherlands, 1066 BE
        • Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
  • United Kingdom
    • England
      • London, England, United Kingdom, EC1A 7BE
        • Saint Bartholomew's Hospital
      • Sutton, England, United Kingdom, SM2 5PT
        • Royal Marsden - Surrey
    • Northern Ireland
      • Belfast, Northern Ireland, United Kingdom, BT9 7BL
        • Centre for Cancer Research and Cell Biology at Queen's University Belfast
    • Scotland
      • Glasgow, Scotland, United Kingdom, G11 6NT
        • Beatson West of Scotland Cancer Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective tumor response rate (complete response or partial response) as assessed by modified RECIST criteria
Time Frame: 28 days prior to baseline, at 10 weeks and at end of treatment
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 Frame: 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.
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
Time Frame: 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.
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
Time Frame: 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.
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
Time Frame: Week 1, Week 10 and end of treatment
Quality of life will be assessed using the Lung Cancer Symptom Score
Week 1, Week 10 and end of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cancer Trials Ireland

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2006

Primary Completion (Actual)

December 1, 2009

Study Registration Dates

First Submitted

August 8, 2007

First Submitted That Met QC Criteria

August 8, 2007

First Posted (Estimate)

August 9, 2007

Study Record Updates

Last Update Posted (Estimate)

December 31, 2014

Last Update Submitted That Met QC Criteria

December 30, 2014

Last Verified

January 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 05-10 ICORG
  • ICORG-05-10
  • EUDRACT-2005-004420-39
  • EU-20748

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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