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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00027703
First received: December 7, 2001
Last updated: February 10, 2014
Last verified: December 2012
  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. 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.


Condition Intervention Phase
Advanced Malignant Mesothelioma
Epithelial Mesothelioma
Localized Malignant Mesothelioma
Recurrent Malignant Mesothelioma
Sarcomatous Mesothelioma
Drug: gemcitabine hydrochloride
Drug: cisplatin
Biological: bevacizumab
Other: placebo
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
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 [ Time Frame: Time from randomization until the first evidence of progression, up to 9 years ] [ Designated as safety issue: No ]
    The two treatment groups will be compared using a stratified logrank test. Kaplan-Meier time-to-event curves will be constructed for each treatment group. Median time-to-progression in each group and corresponding 95% confidence intervals will be derived using the method described in Brookmeyer and Crowley.


Secondary Outcome Measures:
  • Complete response rate [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    Will be compared between groups using chi-square or Fisher exact tests, as appropriate.

  • Objective response rate (complete and partial response) [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    Will be compared between groups using chi-square or Fisher exact tests, as appropriate.

  • Rate of disease stabilization [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    Will be compared between groups using chi-square or Fisher exact tests, as appropriate.

  • Overall survival [ Time Frame: Up to 9 years ] [ Designated as safety issue: No ]
    Kaplan-Meier estimates of overall survival rates will be derived and compared between the two groups using a stratified log-rank test.

  • Incidence of adverse events graded according to NCI CTCAE version 3.0 [ Time Frame: Up to 9 years ] [ Designated as safety issue: Yes ]
    Toxicity rates will be compared between the two groups via chi-square or Fisher exact tests.


Enrollment: 106
Study Start Date: October 2001
Primary Completion Date: May 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Other: laboratory biomarker analysis
Correlative studies
Experimental: 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.
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Other: placebo
Given IV
Other Name: PLCB
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • Performance status - ECOG 0-1
  • More than 3 months
  • 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
  • Bilirubin normal
  • AST/ALT no greater than 2.5 times upper limit of normal
  • INR no greater than 1.5
  • Creatinine no greater than 1.5 mg/dL
  • 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
  • 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
  • See Disease Characteristics
  • No history of pulmonary embolism
  • 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
  • No growth factors for 24 hours before, during, or for 24 hours after cytotoxic chemotherapy
  • See Biologic therapy
  • Prior intrapleural cytotoxic agents (including bleomycin) allowed
  • No prior systemic cytotoxic chemotherapy
  • See Disease Characteristics
  • At least 4 weeks since prior radiotherapy and recovered
  • See Disease Characteristics
  • At least 6 weeks since prior major surgery
  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00027703

Locations
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Sponsors and Collaborators
Investigators
Principal Investigator: Hedy Kindler University of Chicago
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00027703     History of Changes
Other Study ID Numbers: NCI-2012-02430, NCI-2012-02430, CDR0000069058, NCI-2710, UCCRC-11046A, 11046A, 2710, N01CM17102, P30CA014599
Study First Received: December 7, 2001
Last Updated: February 10, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Mesothelioma
Neoplasms, Mesothelial
Lung Neoplasms
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Antibodies
Antibodies, Monoclonal
Gemcitabine
Bevacizumab
Cisplatin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Radiation-Sensitizing Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents

ClinicalTrials.gov processed this record on July 31, 2014