A Phase I Study of Bortezomib and Temozolomide in Patients With Refractory Solid Tumors
- To determine the dose-limiting toxicities and maximum tolerated doses of bortezomib and
temozolomide in patients with recurrent high-grade gliomas, recurrent metastatic brain
tumors, or other refractory solid tumors.
- To evaluate the pharmacokinetics of bortezomib in patients taking hepatic
enzyme-inducing anticonvulsants (Group A) and in those who are not (Group B).
- To describe the proportion of study patients treated with bortezomib and temozolomide
who obtain a confirmed complete response or partial response.
- To report the percentage of patients with 6-month progression-free survival.
OUTLINE: Patients are stratified according to concurrent hepatic enzyme-inducing
anticonvulsants (HEIAs) (Group A) versus concurrent anticonvulsant drugs that cause modest
or no induction of hepatic metabolic enzymes OR no anticonvulsant drugs (Group B).
- Group A: Patients receive oral temozolomide once a day on days 1-5 and bortezomib IV on
days 2, 5, 9, and 12. Courses repeat every 28 days in the absence of disease
progression or unacceptable toxicity.
- Group B: Patients receive temozolomide and bortezomib as in group A. Cohorts of
patients in both groups receive escalating doses of both study drugs until the maximum
tolerated doses are determined.
All patients undergo blood sample collection periodically for pharmacokinetic studies.
Samples are analyzed for bortezomib concentration (groups A and B) and trough levels of
anticonvulsants (group A only).
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Dose-limiting toxicity and maximum tolerated dose
Jana Portnow, MD
Beckman Research Institute
United States: Federal Government
|City of Hope Comprehensive Cancer Center||Duarte, California 91010|
|City of Hope Medical Group||Pasadena, California 91105|