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
18 Years
N/A
Both
Advanced Malignant Mesothelioma, Epithelial Mesothelioma, Localized Malignant Mesothelioma, Recurrent Malignant Mesothelioma, Sarcomatous Mesothelioma
Trial Information
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
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Outcome Measure:
Time to disease progression
Outcome Description:
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; stratum-specific inference for median event times will be performed as described in Karrison.
Outcome Time Frame:
Time from randomization until the first evidence of progression, up to 9 years
Safety Issue:
No
Principal Investigator
Hedy Kindler
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of Chicago Comprehensive Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-02430
NCT ID:
NCT00027703
Start Date:
October 2001
Completion Date:
Related Keywords:
- Advanced Malignant Mesothelioma
- Epithelial Mesothelioma
- Localized Malignant Mesothelioma
- Recurrent Malignant Mesothelioma
- Sarcomatous Mesothelioma
- Mesothelioma
Name | Location |
|---|---|
| University of Chicago Comprehensive Cancer Center | Chicago, Illinois 60637-1470 |
