Bortezomib in Treating Patients With Malignant Pleural Mesothelioma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
ICORG- All Ireland Cooperative Oncology Research Group
ClinicalTrials.gov Identifier:
NCT00513877
First received: August 8, 2007
Last updated: January 24, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Malignant Mesothelioma
Drug: bortezomib
Procedure: quality-of-life assessment
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Phase II Multicentre Clinical Trial of Single Agent Bortezomib in Patients With Malignant Pleural Mesothelioma

Resource links provided by NLM:


Further study details as provided by ICORG- All Ireland Cooperative Oncology Research Group:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: Yes ]
  • Quality of life [ Time Frame: Week 1, Week 10 and end of treatment ] [ Designated as safety issue: No ]
    Quality of life will be assessed using the Lung Cancer Symptom Score


Enrollment: 33
Study Start Date: May 2006
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bortezomib 1.6mg/m2 Drug: bortezomib Procedure: quality-of-life assessment

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00513877

Locations
Belgium
Universitair Ziekenhuis Gent
Ghent, Belgium, B-9000
Ireland
Cork University Hospital
Cork, Ireland
Adelaide and Meath Hospital, Dublin Incorporating the National Children's Hospital
Dublin, Ireland, 24
Mater Misericordiae University Hospital
Dublin, Ireland, 7
St. James's Hospital
Dublin, Ireland, 8
Beaumont Hospital
Dublin, Ireland, 9
St. Vincent's University Hospital
Dublin, Ireland, 4
Galway University Hospital
Galway, Ireland
Netherlands
Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
Amsterdam, Netherlands, 1066 BE
United Kingdom
Saint Bartholomew's Hospital
London, England, United Kingdom, EC1A 7BE
Royal Marsden - Surrey
Sutton, England, United Kingdom, SM2 5PT
Centre for Cancer Research and Cell Biology at Queen's University Belfast
Belfast, Northern Ireland, United Kingdom, BT9 7BL
Beatson West of Scotland Cancer Centre
Glasgow, Scotland, United Kingdom, G11 6NT
Sponsors and Collaborators
ICORG- All Ireland Cooperative Oncology Research Group
Investigators
Principal Investigator: Dean A. Fennell, MD, PhD Centre for Cancer Research and Cell Biology at Queen's University Belfast
  More Information

Additional Information:
No publications provided

Responsible Party: ICORG- All Ireland Cooperative Oncology Research Group
ClinicalTrials.gov Identifier: NCT00513877     History of Changes
Other Study ID Numbers: CDR0000560151, ICORG-05-10, EUDRACT-2005-004420-39, EU-20748
Study First Received: August 8, 2007
Last Updated: January 24, 2013
Health Authority: Ireland: Irish Medicines Board

Keywords provided by ICORG- All Ireland Cooperative Oncology Research Group:
recurrent malignant mesothelioma
stage IA malignant mesothelioma
stage IB malignant mesothelioma
stage II malignant mesothelioma
stage III malignant mesothelioma
stage IV malignant mesothelioma

Additional relevant MeSH terms:
Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014