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Combination Chemotherapy With or Without Bevacizumab in Treating Patients With Malignant Mesothelioma
This study is ongoing, but not recruiting participants.
First Received: December 7, 2001   Last Updated: February 25, 2009   History of Changes
Sponsors and Collaborators: University of Chicago
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00027703
  Purpose

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
Malignant Mesothelioma
Biological: bevacizumab
Drug: cisplatin
Drug: gemcitabine hydrochloride
Phase II

Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Placebo Control
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Time to disease progression at 3 or 4 months [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complete response rate [ Designated as safety issue: No ]
  • Objective response rate (complete and partial response) [ Designated as safety issue: No ]
  • Rate of disease stabilization [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]

Study Start Date: December 2001
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00027703

Locations
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
City of Hope Medical Group
Pasadena, California, United States, 91105
University of California Davis Cancer Center
Sacramento, California, United States, 95817
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90089-9181
United States, Illinois
Cardinal Bernardin Cancer Center at Loyola University Medical Center
Maywood, Illinois, United States, 60153
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
United States, Indiana
CCOP - Northern Indiana CR Consortium
South Bend, Indiana, United States, 46601
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4283
Hillman Cancer Center at University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
M.D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
United States, Wisconsin
Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, United States, 53226
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164
Sponsors and Collaborators
University of Chicago
Investigators
Study Chair: Hedy L. Kindler, MD University of Chicago
  More Information

Additional Information:
Publications:
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.

Study ID Numbers: CDR0000069058, UCCRC-11046A, NCI-2710
Study First Received: December 7, 2001
Last Updated: February 25, 2009
ClinicalTrials.gov Identifier: NCT00027703     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
localized malignant mesothelioma
advanced malignant mesothelioma
recurrent malignant mesothelioma
epithelial mesothelioma
sarcomatous mesothelioma

Study placed in the following topic categories:
Antimetabolites
Immunologic Factors
Bevacizumab
Antiviral Agents
Immunosuppressive Agents
Angiogenesis Inhibitors
Recurrence
Cisplatin
Radiation-Sensitizing Agents
Mesothelioma
Gemcitabine
Adenoma
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Neoplasms, Mesothelial
Physiological Effects of Drugs
Bevacizumab
Cisplatin
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents
Gemcitabine
Neoplasms by Histologic Type
Growth Substances
Enzyme Inhibitors
Antiviral Agents
Immunosuppressive Agents
Angiogenesis Inhibitors
Pharmacologic Actions
Neoplasms
Radiation-Sensitizing Agents
Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on July 02, 2009