MedPath

ZD6474 to Treat Advanced Brain Cancer in Patients

Phase 1
Completed
Conditions
Recurrent High-Grade Gliomas
Progressive Low-Grade Gliomas
Malignant Gliomas
Registration Number
NCT00272350
Lead Sponsor
National Cancer Institute (NCI)
Brief Summary

Background:

In vivo experiments have documented the ability of ZD6474 to inhibit tumor growth in various preclinical tumor models. Given the pronounced neovasculature associated with malignant gliomas, and abundant published data demonstrating the dependence of glioma growth on the maintenance and proliferation of this neovasculature, ZD6474 represents a potentially promising new therapeutic approach to these otherwise refractory tumors.

Thus, we now propose a phase I trial of ZD6474 in patients with recurrent and progressive low-grade gliomas who are on P450-inducing anti-epileptic drugs and a phase II trial for patients with recurrent gliomas not taking P450-inducing anti-epileptic drugs.

Objective:

Phase I - To establish the maximally tolerated dose of ZD6474 and to obtain preliminary information regarding the spectrum of toxicities of ZD6474, and to obtain pharmacokinetic data to patients taking EIAED.

Phase I - To obtain preliminary information regarding potential anti-tumor activity of ZD6474 in patients taking EIAED.

Phase II - To establish data regarding the anti-tumor activity of ZD6474 and to collect information regarding the spectrum of toxicities in patients not taking EIAEDs.

Eligibility:

Patients with histologically proven malignant primary gliomas will be eligible for this protocol. Additionally, patients with progressive low-grade gliomas and patients with infiltrative brain stem gliomas, diagnosed radiographically rather than by biopsy will also be eligible.

Design:

Phase I - Group B patients will be accrued to the formal dose-escalation phase I trial. Groups of patients with recurrent high-grade gliomas will be accrued to increasingly higher doses of ZD6474 until the MTD is established.

Phase II - Patients will be treated at a dose of 300 mg day, every day, on a 4-week cycle.

Detailed Description

Background:

In vivo experiments have documented the ability of ZD6474 to inhibit tumor growth in various preclinical tumor models. Given the pronounced neovasculature associated with malignant gliomas, and abundant published data demonstrating the dependence of glioma growth on the maintenance and proliferation of this neovasculature, ZD6474 represents a potentially promising new therapeutic approach to these otherwise refractory tumors.

Thus, we now propose a phase I trial of ZD6474 in patients with recurrent and progressive low-grade gliomas who are on P450-inducing anti-epileptic drugs and a phase II trial for patients with recurrent gliomas not taking P450-inducing anti-epileptic drugs.

Objective:

Phase I - To establish the maximally tolerated dose of ZD6474 and to obtain preliminary information regarding the spectrum of toxicities of ZD6474, and to obtain pharmacokinetic data to patients taking EIAED.

Phase I - To obtain preliminary information regarding potential anti-tumor activity of ZD6474 in patients taking EIAED.

Phase II - To establish data regarding the anti-tumor activity of ZD6474 and to collect information regarding the spectrum of toxicities in patients not taking EIAEDs.

Eligibility:

Patients with histologically proven malignant primary gliomas will be eligible for this protocol. Additionally, patients with progressive low-grade gliomas and patients with infiltrative brain stem gliomas, diagnosed radiographically rather than by biopsy will also be eligible.

Design:

Phase I - Group B patients will be accrued to the formal dose-escalation phase I trial. Groups of patients with recurrent high-grade gliomas will be accrued to increasingly higher doses of ZD6474 until the MTD is established.

Phase II - Patients will be treated at a dose of 300 mg day, every day, on a 4-week cycle.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
83
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
To establish the maximally tolerated dose of ZD6474 in patients with recurrent high-grade gliomas taking EIAED.
Secondary Outcome Measures
NameTimeMethod
To obtain preliminary information regarding the spectrum of toxicities, and to obtain pharmacokinetic data on ZD6474 administered to patients with recurrent high-grade gliomas taking EIAED.

Trial Locations

Locations (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

🇺🇸

Bethesda, Maryland, United States

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