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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00093613
Other study ID # NCI-2012-03102
Secondary ID NCI-2012-03102NA
Status Completed
Phase Phase 1
First received October 6, 2004
Last updated May 29, 2014
Start date December 2004
Est. completion date December 2011

Study information

Verified date December 2013
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial Summary

This phase I trial is studying the side effects and best dose of sorafenib in treating patients with recurrent or progressive malignant glioma. Sorafenib may stop the growth of tumor cells by stopping blood flow to the tumor and by blocking the enzymes necessary for their growth.


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.


Recruitment information / eligibility

Status Completed
Enrollment 47
Est. completion date December 2011
Est. primary completion date October 2010
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility 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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Intervention

Drug:
sorafenib tosylate
Given PO
Other:
pharmacological study
Correlative studies

Locations

Country Name City State
United States Emory University/Winship Cancer Institute Atlanta Georgia
United States Adult Brain Tumor Consortium Baltimore Maryland
United States Johns Hopkins University/Sidney Kimmel Cancer Center Baltimore Maryland
United States University of Alabama at Birmingham Birmingham Alabama
United States Massachusetts General Hospital Cancer Center Boston Massachusetts
United States Cleveland Clinic Foundation Cleveland Ohio
United States Henry Ford Hospital Detroit Michigan
United States University of Pennsylvania/Abramson Cancer Center Philadelphia Pennsylvania
United States H. Lee Moffitt Cancer Center and Research Institute Tampa Florida
United States Wake Forest University Health Sciences Winston-Salem North Carolina

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 28 days Yes
Secondary Frequency of the toxicities associated with sorafenib tosylate treatment between patients with recurrent or progressive malignant glioma, receiving or not receiving anticonvulsants The proportion of patients with serious or life threatening toxicities will be estimated along with 95% confidence intervals. Up to 6 years Yes
Secondary Effect of taking enzyme inducing anticonvulsant drugs on the pharmacokinetics and metabolism of sorafenib tosylate 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. Days 1 and 15 of course 1 and day 15 of course 2 No
Secondary Magnitude of variability in the steady-state pharmacokinetics of the drug both within and between patients 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. Days 1 and 15 of course 1 and day 15 of course 2 No
Secondary Overall survival 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). From the time of first day of treatment to death occurrence, assessed up to 6 years No
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