Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Related Information
Registry Information

Alternate Title

Combination Chemotherapy With or Without Bevacizumab in Treating Patients With Malignant Mesothelioma

Basic Trial Information

Special Category: NCI Web site featured trial

Objectives

1. Compare the time to progression of patients with malignant mesothelioma treated with gemcitabine and cisplatin with or without bevacizumab.
2. Compare the objective response rate in patients treated with these regimens.
3. Compare the toxicity of these regimens when administered to these patients.
4. Compare the median and overall survival of patients treated with these regimens.
5. 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.

Entry 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

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

Patient Characteristics:

Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• More than 3 months

Hematopoietic:

• WBC at least 3,000/mm³
• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• 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

Expected Enrollment

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

Outcomes

Time to disease progression at 3 or 4 months

Complete response rate
Objective response rate (complete and partial response)
Rate of disease stabilization
Overall survival
Toxicity

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.

Kindler HL, Karrison T, Lu C, et al.: A multicenter, double-blind, placebo-controlled randomized phase II trial of gemcitabine/cisplatin (GC) plus bevacizumab (B) or placebo in patients (pts) with malignant mesothelioma (MM). [Abstract] J Clin Oncol 23 (Suppl 16): A-7019, 625s, 2005.

Trial Contact Information

Trial Lead Organizations

University of Chicago Cancer Research Center

Hedy Kindler, MD, Protocol chair		Ph: 773-702-0360; 888-824-0200

Related Information

Featured trial article

Registry Information
Official Title		A Double Blind, Placebo Controlled Randomized Phase II Trial Of Gemcitabine And Cisplatin With Or Without The VEGF Inhibitor Bevacizumab (NSC #704865) In Patients With Malignant Mesotheloma
Trial Start Date		2001-12-05
Trial Completion Date		2010-08-17
Registered in ClinicalTrials.gov		NCT00027703
Date Submitted to PDQ		2001-10-11
Information Last Verified		2005-06-02
NCI Grant/Contract Number		CM17102, CA14599, CA63187

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