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

(Summary Last Modified October 2005)

http://www.clinicaltrials.gov/ct/show/NCT00027703?amp;order=1

This study is currently recruiting patients.

Sponsored by
National Cancer Institute (NCI)
University of Chicago Cancer Research Center

PURPOSE

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as bevacizumab can locate tumor cells and kill them without harming normal cells. It is not yet known if combination chemotherapy is more effective with or without bevacizumab in treating malignant mesothelioma .

PURPOSE: Randomized phase II trial to compare the effectiveness of combination chemotherapy works better with or without bevacizumab in treating patients who have malignant mesothelioma.

Study Type: Interventional
Stuey Design: Treatment

Official Title: Phase II Randomized Study of Gemcitabine and Cisplatin With or Without Bevacizumab in Patients With Malignant Mesothelioma

Further Study Details:

OBJECTIVES:

I. Compare the time to progression of patients with malignant mesothelioma treated with gemcitabine and cisplatin with or without bevacizumab.

II. Compare the objective response rate in patients treated with these regimens.

III. Compare the toxicity of these regimens when administered to these patients.

IV. Compare the median and overall survival of patients treated with these regimens.

V. 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.

PROTOCOL 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.

ELIGIBILITY

Ages Eligible for Study: 18 Years and above

Criteria

PROTOCOL 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

--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 of deep vein thrombosis
    No myocardial ischemia or infarction 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
    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

LOCATION AND CONTACT INFORMATION

California

City of Hope Comprehensive Cancer Center
Duarte, California, 91010-3000
United States; Recruiting
Clinical Trials Office - New Patient Services 800-826-4673 becomingapatient@coh.org

City of Hope Medical Group
Pasadena, California, 91105
United States; Recruiting
Mark V. McNamara, MD 626-396-2900 mmcnamara@ccsmg.com

University of California Davis Cancer Center
Sacramento, California, 95817
United States; Recruiting
david R. Gandara, MD 916-734-3772 dgandara@cc.ucdmc.ucdavis.edu

USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, 90033-0804
United States; Recruiting
David I. Quinn, MD 323-865-0456 diquinn@hsc.usc.edu

Illinois

Cardinal Bernardin Cancer Center at Loyola University Medical Center
Maywood, Illinois, 60153
United States; Recruiting
Joseph I. Clark, MD 708-327-3236 jclark@lumc.edu

University of Chicago Cancer Research Center
Chicago, Illinois, 60637-1470
United States; Recruiting
Hedy L. Kindler, MD 773-702-0360

Indiana

CCOP - Northern Indiana CR Consortium
South Bend, Indiana, 46601
United States; Recruiting
David Allen Taber, MD 574-237-1328

Maryland

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231-1000
United States; Recruiting
Julie Brahmer, MD 410-502-7159

Massachusetts

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, 02115
United States; Recruiting
Pasi Janne, MD, PhD 617-632-6076 pjanne@partners.org

Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
United States; Recruiting
Panos Fidias, MD 617-726-9298 pfidias2@partners.org

Michigan

Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201-1379
United States; Recruiting
Shirish M. Gadgeel, MD 313-745-8389 gadgeels@karmanos.org

New York

Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
United States; Recruiting
Lee M. Krug, MD 212-639-8420

Pennsylvania

Abramson Cancer Center at the University of Pennsylvania
Philadelphia, Pennsylvania, 19104-4283
United States; Recruiting
James Stevenson, MD 215-662-6682

Hillman Cancer Center at University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, 15236
United States; Recruiting
Chandra Prakash Belani, MD 412-648-6619 belanicp@upmc.edu

Texas

University of Texas - MD Anderson Cancer Center
Houston, Texas, 77230-1402
United States; Recruiting
Charles Lu, MD 713-792-6363 clu@mdanderson.org

Wisconsin

Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, 53226
United States; Recruiting
Stuart J. Wong, MD 414-805-4603

University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, 53792
United States; Recruiting
Anne Traynor, MD 608-263-5389

Study chairs or principal investigators

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

More Information

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

Study ID Numbers: CDR0000069058; UCCRC-11046A; NCI-2710; NCT00027703
Record last reviewed: October 20, 2005
Record first received: December 7, 2001
ClinicalTrials.gov Identifier: NCT00027703
Health Authority: United States: Federal Government

** FIRST POSTED MAY 3, 2002 **
** RE-POSTED JANUARY 18, 2005 **
** RE-POSTED AUGUST 8, 2005 **
** RE-POSTED NOVEMBER 0, 2005 **