Back to resultsBortezomib and Cisplatin as First-Line Therapy in Treating Patients With Malignant Mesothelioma
Primary Purpose
Malignant Mesothelioma
Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
bortezomib
cisplatin
Sponsored by
About this trial
This is an interventional treatment trial for Malignant Mesothelioma focused on measuring localized malignant mesothelioma, recurrent malignant mesothelioma, advanced malignant mesothelioma
Eligibility Criteria
DISEASE CHARACTERISTICS:
Histologically confirmed pleural malignant mesothelioma, meeting 1 of the following criteria:
- Recurrent disease after radical surgery
- Disease not considered suitable for radical treatment
- Measurable or evaluable disease
- No clinical evidence of brain or leptomeningeal metastases
PATIENT CHARACTERISTICS:
- WHO performance status 0-1
- Life expectancy > 12 weeks
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Absolute neutrophil count > 1,500/mm³
- Platelet count > 100,000/mm³
- Creatinine clearance > 60 mL/min OR > 50 mL/min
- ALT and AST < 2.5 times upper limit of normal (ULN) (< 5 times ULN if liver metastases present)
- Bilirubin < 1.5 times ULN
- No concurrent secondary malignancy except carcinoma in situ of the cervix or adequately treated basal cell skin cancer
No other malignancy treated within the past 5 years
- Melanoma, breast cancer, or hypernephroma treated within the past 5 years and without recurrence are allowed
No uncontrolled or severe cardiovascular disease, including any of the following:
- Myocardial infarction within the past 6 months
- New York Heart Association class III-IV heart failure
- Uncontrolled angina
- Clinically significant pericardial disease or cardiac amyloidosis
- No infiltrative pulmonary or pericardial disease
- No preexisting peripheral neuropathy
- No known or suspected allergy or intolerance to boron, mannitol, or heparin, if an indwelling catheter is used
- No psychological, familial, sociological, or geographical condition that would preclude protocol compliance
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior systemic chemotherapy for mesothelioma
- No other concurrent antineoplastic agents except medications that may have antineoplastic activity but are taken for other reasons (e.g., megestrol acetate, cyclooxygenase-2 inhibitors, or bisphosphonates)
- No other concurrent experimental agents
Sites / Locations
- Royal Marsden - Surrey
Outcomes
Primary Outcome Measures
Progression-free survival (PFS) rate at 18 weeks
Secondary Outcome Measures
Overall objective response rate
Symptomatic response rate
Safety as measured by NCI CTCAE v3.0 and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity questionnaire
Duration of PFS
Overall survival
Full Information
NCT ID
NCT00458913
First Posted
April 9, 2007
Last Updated
July 11, 2018
Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
1. Study Identification
Unique Protocol Identification Number
NCT00458913
Brief Title
Bortezomib and Cisplatin as First-Line Therapy in Treating Patients With Malignant Mesothelioma
Official Title
Phase II Study of Bortezomib (VELCADE) With Cisplatin as First Line Treatment of Malignant Mesothelioma
Study Type
Interventional
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
February 2007 (undefined)
Primary Completion Date
April 2010 (Actual)
Study Completion Date
March 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
4. Oversight
5. Study Description
Brief Summary
RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with cisplatin may kill more tumor cells.
PURPOSE: This phase II trial is studying the side effects and how well giving bortezomib together with cisplatin works as first-line therapy in treating patients with malignant mesothelioma.
Detailed Description
OBJECTIVES:
Determine the activity and safety of bortezomib and cisplatin as first-line treatment in patients with malignant mesothelioma.
Validate the use of progression-free survival rate as a primary endpoint for the design of phase II mesothelioma trials.
OUTLINE: This is a nonrandomized, open-label, multicenter study.
Patients receive cisplatin IV over 1 hour on day 1 and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed periodically.
PROJECTED ACCRUAL: A total of 76 patients will be accrued for this study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Mesothelioma
Keywords
localized malignant mesothelioma, recurrent malignant mesothelioma, advanced malignant mesothelioma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
82 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
bortezomib
Intervention Type
Drug
Intervention Name(s)
cisplatin
Primary Outcome Measure Information:
Title
Progression-free survival (PFS) rate at 18 weeks
Secondary Outcome Measure Information:
Title
Overall objective response rate
Title
Symptomatic response rate
Title
Safety as measured by NCI CTCAE v3.0 and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity questionnaire
Title
Duration of PFS
Title
Overall survival
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS:
Histologically confirmed pleural malignant mesothelioma, meeting 1 of the following criteria:
Recurrent disease after radical surgery
Disease not considered suitable for radical treatment
Measurable or evaluable disease
No clinical evidence of brain or leptomeningeal metastases
PATIENT CHARACTERISTICS:
WHO performance status 0-1
Life expectancy > 12 weeks
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Absolute neutrophil count > 1,500/mm³
Platelet count > 100,000/mm³
Creatinine clearance > 60 mL/min OR > 50 mL/min
ALT and AST < 2.5 times upper limit of normal (ULN) (< 5 times ULN if liver metastases present)
Bilirubin < 1.5 times ULN
No concurrent secondary malignancy except carcinoma in situ of the cervix or adequately treated basal cell skin cancer
No other malignancy treated within the past 5 years
Melanoma, breast cancer, or hypernephroma treated within the past 5 years and without recurrence are allowed
No uncontrolled or severe cardiovascular disease, including any of the following:
Myocardial infarction within the past 6 months
New York Heart Association class III-IV heart failure
Uncontrolled angina
Clinically significant pericardial disease or cardiac amyloidosis
No infiltrative pulmonary or pericardial disease
No preexisting peripheral neuropathy
No known or suspected allergy or intolerance to boron, mannitol, or heparin, if an indwelling catheter is used
No psychological, familial, sociological, or geographical condition that would preclude protocol compliance
PRIOR CONCURRENT THERAPY:
See Disease Characteristics
No prior systemic chemotherapy for mesothelioma
No other concurrent antineoplastic agents except medications that may have antineoplastic activity but are taken for other reasons (e.g., megestrol acetate, cyclooxygenase-2 inhibitors, or bisphosphonates)
No other concurrent experimental agents
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mary O'Brien, MD
Organizational Affiliation
Royal Marsden NHS Foundation Trust
Official's Role
Study Chair
Facility Information:
Facility Name
Royal Marsden - Surrey
City
Sutton
State/Province
England
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
31576173
Citation
Walter RFH, Sydow SR, Berg E, Kollmeier J, Christoph DC, Christoph S, Eberhardt WEE, Mairinger T, Wohlschlaeger J, Schmid KW, Mairinger FD. Bortezomib sensitivity is tissue dependent and high expression of the 20S proteasome precludes good response in malignant pleural mesothelioma. Cancer Manag Res. 2019 Sep 24;11:8711-8720. doi: 10.2147/CMAR.S194337. eCollection 2019.
Results Reference
derived
PubMed Identifier
23791541
Citation
O'Brien ME, Gaafar RM, Popat S, Grossi F, Price A, Talbot DC, Cufer T, Ottensmeier C, Danson S, Pallis A, Hasan B, Van Meerbeeck JP, Baas P. Phase II study of first-line bortezomib and cisplatin in malignant pleural mesothelioma and prospective validation of progression free survival rate as a primary end-point for mesothelioma clinical trials (European Organisation for Research and Treatment of Cancer 08052). Eur J Cancer. 2013 Sep;49(13):2815-22. doi: 10.1016/j.ejca.2013.05.008. Epub 2013 Jun 20.
Results Reference
derived
Learn more about this trial
Bortezomib and Cisplatin as First-Line Therapy in Treating Patients With Malignant Mesothelioma
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