- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00093613
Sorafenib in Treating Patients With Recurrent or Progressive Malignant Glioma
A Phase I Trial of BAY 43-9006 for Patients With Recurrent or Progressive Malignant Glioma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) of BAY 43-9006 when administered to adults with recurrent malignant glioma, receiving (Group A) or not receiving (Group B) anticonvulsants known to be metabolized by the P450 hepatic enzyme complex.
II. To assess and estimate the dose-related toxicities. III. To describe the pharmacokinetics of this route of administration, measuring BAY 43-9006, and to assess the pharmacokinetic difference between patients taking enzyme-inducing agents and those who are not.
IV. To estimate overall survival.
OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to the concurrent use of cytochrome P450-inducing anticonvulsants (yes vs no).
Patients receive oral sorafenib twice daily on days 1-28 (once daily on day 1 of course 1 only). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients per stratum receive escalating doses of sorafenib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity.
Patients are followed every 2 months.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Alabama
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Birmingham, Alabama, United States, 35294
- University of Alabama at Birmingham
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Florida
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Tampa, Florida, United States, 33612
- H. Lee Moffitt Cancer Center and Research Institute
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Georgia
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Atlanta, Georgia, United States, 30322
- Emory University/Winship Cancer Institute
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Maryland
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Baltimore, Maryland, United States, 21287
- Johns Hopkins University/Sidney Kimmel Cancer Center
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Baltimore, Maryland, United States, 21231-1000
- Adult Brain Tumor Consortium
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Massachusetts
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Boston, Massachusetts, United States, 02114
- Massachusetts General Hospital Cancer Center
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Michigan
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Detroit, Michigan, United States, 48202
- Henry Ford Hospital
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North Carolina
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Winston-Salem, North Carolina, United States, 27157
- Wake Forest University Health Sciences
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Ohio
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Cleveland, Ohio, United States, 44195
- Cleveland Clinic Foundation
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- University of Pennsylvania/Abramson Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients must have histologically proven malignant glioma (anaplastic astrocytoma, anaplastic oligodendroglioma or glioblastoma multiforme) which is progressive or recurrent after radiation therapy ± chemotherapy; patients with previous low grade glioma who progressed after radiotherapy ± chemotherapy and are biopsied and found to have a high grade glioma are eligible
- Patients must have measurable progressive or recurrent malignant glioma by MRI or CT imaging; (Within 14 days before starting treatment)
- Patients must have recovered from toxicity of prior therapy; an interval of at least 3 months must have elapsed since the completion of the most recent course of radiation therapy, while at least 3 weeks must have elapsed since the completion of a non-nitrosourea containing chemotherapy regimen, and at least 6 weeks since the completion of a nitrosourea containing chemotherapy regimen
- Patients must have a Karnofsky performance status >= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
- Absolute Neutrophil Count >= 1500/mm^3
- Platelets >= 100,000/mm^3
- Creatinine =< 1.7mg/dl
- Total Bilirubin =< 1.5mg/dl
- Transaminases =< 4 times above the upper limits of the institutional norm
- PT, PTT, INR within institutional norm
- Patients must be able to provide written informed consent
- Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception; women of childbearing potential must have a negative serum pregnancy test; (The anti-proliferative activity of this experimental drug may be harmful to the developing fetus or nursing infant)
- Patients must have a Mini Mental State Exam score >= 15
Exclusion Criteria:
- Patients with serious concurrent infection or medical illness which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety; (Examples of medical illnesses are [but not limited to] the following: uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements)
- Patients who are pregnant or breast-feeding; (The anti-proliferative activity of this experimental drug may be harmful to the developing fetus or nursing infant)
- Patients who have received more than two prior treatments
- Patients receiving concurrent therapy for their tumor (with the exception of steroids)
- Patients with a concurrent malignancy are ineligible unless they are patients with curatively treated carcinoma-in-situ or basal cell carcinoma of the skin; patients with a prior malignancy are ineligible unless they have been free of disease for >= five years
- Patients must not have any evidence of bleeding diathesis
- Patients must not be on therapeutic anticoagulation; prophylactic anticoagulation (i.e. low dose warfarin) of venous or arterial access devices is allowed provided that the requirements for PT, INR or PTT are met; (Patients will be taken off treatment if they require therapeutic anticoagulation during BAY 43-9006 treatment)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (sorafenib tosylate)
Patients receive oral sorafenib twice daily on days 1-28 (once daily on day 1 of course 1 only). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients per stratum receive escalating doses of sorafenib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity. |
Correlative studies
Other Names:
Given PO
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Maximum tolerated dose (MTD) of sorafenib tosylate in patients with recurrent or progressive malignant glioma, receiving (group A) or not receiving (group B) anticonvulsants known to be metabolized by the P450 hepatic enzyme complex
Time Frame: 28 days
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28 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Frequency of the toxicities associated with sorafenib tosylate treatment between patients with recurrent or progressive malignant glioma, receiving or not receiving anticonvulsants
Time Frame: Up to 6 years
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The proportion of patients with serious or life threatening toxicities will be estimated along with 95% confidence intervals.
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Up to 6 years
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Effect of taking enzyme inducing anticonvulsant drugs on the pharmacokinetics and metabolism of sorafenib tosylate
Time Frame: Days 1 and 15 of course 1 and day 15 of course 2
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The geometric mean +/- standard deviation of the estimated values of the pharmacokinetic parameter for groups of patients evaluated at each dose level will be calculated.
Parametric statistical tests (ie, single factor ANOVA, Student's t-test) of pharmacokinetic variables will be performed after logarithmic transformation of the data.
All tests will be two-sided and a value of P < 0.05 will be used as the criteria for significance.
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Days 1 and 15 of course 1 and day 15 of course 2
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Magnitude of variability in the steady-state pharmacokinetics of the drug both within and between patients
Time Frame: Days 1 and 15 of course 1 and day 15 of course 2
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The geometric mean +/- standard deviation of the estimated values of the pharmacokinetic parameter for groups of patients evaluated at each dose level will be calculated.
Parametric statistical tests (ie, single factor ANOVA, Student's t-test) of pharmacokinetic variables will be performed after logarithmic transformation of the data.
All tests will be two-sided and a value of P < 0.05 will be used as the criteria for significance.
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Days 1 and 15 of course 1 and day 15 of course 2
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Overall survival
Time Frame: From the time of first day of treatment to death occurrence, assessed up to 6 years
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Non-parametric estimates of survival will be calculated.
An overall failure rate will be estimated along with the 95% confidence interval.
The overall failure rate is expressed as hazard of failure per person-year of follow-up (the number of deaths divided by the total exposure time in the study cohort).
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From the time of first day of treatment to death occurrence, assessed up to 6 years
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Louis Nabors, National Cancer Institute (NCI)
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Glandular and Epithelial
- Disease Attributes
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Glioblastoma
- Recurrence
- Glioma
- Astrocytoma
- Gliosarcoma
- Oligodendroglioma
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Sorafenib
Other Study ID Numbers
- NCI-2012-03102 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- U01CA062475 (U.S. NIH Grant/Contract)
- NABTT-0401 (Other Identifier: CTEP)
- ABTC-0401
- NABTT 0401 (Other Identifier: Adult Brain Tumor Consortium)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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