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

Study Primary Completion Date: December 2009

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.

Intervention(s) in this Clinical Trial

• Drug: bortezomib
• Drug: cisplatin

Primary Measures

• Progression-free survival (PFS) rate at 18 weeks
  • Safety Issue?: No

Secondary Measures

• Overall objective response rate
  • Safety Issue?: No
• Symptomatic response rate
  • Safety Issue?: No
• Safety as measured by NCI CTCAE v3.0 and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity questionnaire
  • Safety Issue?: Yes
• Duration of PFS
  • Safety Issue?: No
• Overall survival
  • Safety Issue?: No

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 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: European Organization for Research and Treatment of Cancer

Overall Clinical Trial Officials and Contacts

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

Information obtained from ClinicalTrials.gov on October 10, 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