Bortezomib and Cisplatin as First-Line Therapy in Treating Patients With Malignant Mesothelioma

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC (Other)

Overall Status

Completed

CT.gov ID

NCT00458913

Collaborator

(none)

Enrollment

Location

60.9

Duration (Months)

1.3

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Malignant Mesothelioma	Drug: bortezomib Drug: cisplatin	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

82 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Study of Bortezomib (VELCADE) With Cisplatin as First Line Treatment of Malignant Mesothelioma

Study Start Date :

Feb 1, 2007

Actual Primary Completion Date :

Apr 1, 2010

Actual Study Completion Date :

Mar 1, 2012

Outcome Measures

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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