Treating Patients With Malignant Mesothelioma Clinical Study Is Currently Recruiting Patients

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. It is not yet known if combination chemotherapy works better with or without bevacizumab in treating malignant mesothelioma.

PURPOSE: This randomized phase II trial is to see if combination chemotherapy works better with or without bevacizumab in treating patients who have malignant mesothelioma.

Condition	Intervention	Phase
localized malignant mesothelioma advanced malignant mesothelioma recurrent malignant mesothelioma epithelial mesothelioma sarcomatous mesothelioma	Drug: bevacizumab  Drug: cisplatin  Drug: gemcitabine  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: growth factor antagonist therapy  Procedure: monoclonal antibody therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Compare the time to progression of patients with malignant mesothelioma treated with gemcitabine and cisplatin with or without bevacizumab.
• Compare the objective response rate in patients treated with these regimens.
• Compare the toxicity of these regimens when administered to these patients.
• Compare the median and overall survival of patients treated with these regimens.
• Assess plasma vascular endothelial growth factor and serum vascular cell adhesion molecule-1 levels before, during, and after study therapy as predictors of outcome in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to histology (epithelial vs other) and ECOG performance status (0 vs 1). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive gemcitabine IV over 30 minutes on days 1 and 8 and cisplatin IV over 30-60 minutes (beginning after gemcitabine infusion) and bevacizumab IV over 30-90 minutes (beginning after cisplatin infusion) on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve stable disease (SD), complete response (CR), or partial response (PR) after the sixth course may receive bevacizumab as a single agent once every 3 weeks in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive gemcitabine and cisplatin as in arm I and placebo IV over 30-90 minutes (beginning after cisplatin infusion) on day 1. Treatment repeats as in arm I. Patients who achieve SD, CR, or PR after the sixth course may receive placebo as a single agent once every 3 weeks in the absence of disease progression.

PROJECTED ACCRUAL: A total of 106 patients (53 per treatment arm) will be accrued for this study within 16 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed malignant pleural or peritoneal mesothelioma that is not amenable to curative surgery
• Epithelial, sarcomatoid, or mixed subtype
• Evidence of gross unresectability, including, but not limited to, the following conditions:
• Direct extension into the chest wall
• Mediastinal or hilar lymphadenopathy
• Pulmonary or cardiac function that is inadequate to tolerate resection
• Sarcomatoid or mixed histology
• Pleural mesothelioma must be stage II or greater using the International Mesothelioma Interest Group staging system
• Measurable disease outside prior irradiation port
• At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
• Pleural effusions and ascites are not considered measurable lesions
• Site in pleura, lung, liver, or retroperitoneum that can be assessed by MRI for evaluation of blood flow
• No obvious tumor involvement of major vessels by CT scan
• No known brain metastases

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• More than 3 months

Hematopoietic:

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• No history of bleeding diathesis

Hepatic:

• Bilirubin normal
• AST/ALT no greater than 2.5 times upper limit of normal
• INR no greater than 1.5

Renal:

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance at least 60 mL/min
• If 1+ or greater proteinuria on dipstick, then must have less than 500 mg of protein/24-hour urine collection
• No significant renal impairment

Cardiovascular:

• See Disease Characteristics
• No history deep vein thrombosis
• No myocardial ischemia or infarction within the past 6 months
• No uncompensated coronary artery disease within the past 6 months
• No uncontrolled hypertension
• No symptomatic congestive heart failure
• No unstable angina pectoris within the past 6 months
• No cardiac arrhythmia
• No transient ischemic attack within the past 6 months
• No cerebrovascular accident within the past 6 months
• No other arterial thromboembolic event within the past 6 months
• No clinically significant peripheral artery disease

Pulmonary:

• See Disease Characteristics
• No history of pulmonary embolism

Other:

• No prior allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab or other study agents
• No other active malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
• No ongoing or active infection
• No other concurrent uncontrolled illness that would preclude study participation
• No psychiatric illness or social situations that would preclude compliance
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No growth factors for 24 hours before, during, or for 24 hours after cytotoxic chemotherapy

Chemotherapy:

• See Biologic therapy
• Prior intrapleural cytotoxic agents (including bleomycin) allowed
• No prior systemic cytotoxic chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered

Surgery:

• See Disease Characteristics
• At least 6 weeks since prior major surgery

Other:

• At least 30 days since prior investigational drug
• No other concurrent investigational or commercial agents or therapies
• No concurrent combination antiretroviral therapy for HIV-positive patients

Please refer to this study by ClinicalTrials.gov identifier  NCT00027703

California
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States; Recruiting
      City of Hope Medical Group, Pasadena,  California,  91105,  United States; Recruiting
      University of California Davis Cancer Center, Sacramento,  California,  95817,  United States; Recruiting
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033-0804,  United States; Recruiting
Florida
      Mayo Clinic - Jacksonville, Jacksonville,  Florida,  32224,  United States; Recruiting
Illinois
      Cardinal Bernardin Cancer Center at Loyola University Medical Center, Maywood,  Illinois,  60153,  United States; Recruiting
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States; Recruiting
Indiana
      CCOP - Northern Indiana CR Consortium, South Bend,  Indiana,  46601,  United States; Recruiting
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231-1000,  United States; Recruiting
Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
      Massachusetts General Hospital Cancer Center, Boston,  Massachusetts,  02114,  United States; Recruiting
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States; Recruiting
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting
New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting
Pennsylvania
      Abramson Cancer Center of the University of Pennsylvania, Philadelphia,  Pennsylvania,  19104-4283,  United States; Recruiting
      Hillman Cancer Center at University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15232,  United States; Recruiting
Texas
      M.D. Anderson Cancer Center at University of Texas, Houston,  Texas,  77230-1402,  United States; Recruiting
Wisconsin
      Medical College of Wisconsin Cancer Center, Milwaukee,  Wisconsin,  53226,  United States; Recruiting
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792,  United States; Recruiting

Study chairs or principal investigators

Hedy L. Kindler, MD,  Study Chair,  University of Chicago Cancer Research Center