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

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:...

Date First Received: April 9, 2007

Last Updated: March 18, 2008

Verified by: National Cancer Institute (NCI), April 2007

Clinical Trial Phase: Phase 2 | Start Date: February 2007

Overall Status: Recruiting

Estimated Enrollment: 76

Brief Summary

Official Title: “Phase II Study of Bortezomib (VELCADE) With Cisplatin as First Line Treatment of Malignant Mesothelioma”

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.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label

Detailed Clinical Trial 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 every 3 months.

PROJECTED ACCRUAL: A total of 76 patients will be accrued for this study.

Outcome Measures for this Clinical Trial

Primary:

• Progression-free survival (PFS) rate at 18 weeks

Secondary:

• 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

Criteria for Participation in this Clinical Trial

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 <>
• Bilirubin <>
• 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 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

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: European Organization for Research and Treatment of Cancer

Royal Marsden - Surrey

Sutton England SM2 5PT United Kingdom

Overall Clinical Trial Officials and Contacts

Mary O'Brien, MD Study Chair Royal Marsden - Surrey

Additional Information

Information obtained from ClinicalTrials.gov on April 01, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00458913

Study ID Number: CDR0000538677

ClinicalTrials.gov Identifier: NCT00458913

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database

Clinical Trials Authorship and Review

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Labels: ClinicalTrial