Sorafenib in Treating Patients With Recurrent or Progressive Malignant Glioma

NCT ID: NCT00093613

Last Updated: 2014-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-12-31
• Study Completion Date: 2011-12-31

Brief 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.

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.

Conditions

Adult Anaplastic Astrocytoma; Adult Anaplastic Oligodendroglioma; Adult Giant Cell Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

sorafenib tosylate

Intervention Type: DRUG

Given PO

pharmacological study

Intervention Type: OTHER

Correlative studies

Interventions

sorafenib tosylate

Given PO

Intervention Type: DRUG

pharmacological study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

BAY 43-9006; BAY 43-9006 Tosylate Salt; BAY 54-9085; Nexavar; SFN; pharmacological studies

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Louis Nabors

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 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

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Henry Ford Hospital

Detroit, Michigan, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

NCI-2012-03102

Identifier Type: REGISTRY

Identifier Source: secondary_id

NABTT-0401

Identifier Type: -

Identifier Source: secondary_id

ABTC-0401

Identifier Type: -

Identifier Source: secondary_id

NABTT 0401

Identifier Type: OTHER

Identifier Source: secondary_id

NABTT-0401

Identifier Type: OTHER

Identifier Source: secondary_id

U01CA062475

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-03102

Identifier Type: -

Identifier Source: org_study_id