AEE788 and Everolimus in Treating Patients With Recurrent or Relapsed Glioblastoma Multiforme

Brain and Central Nervous System Tumors Clinical Trial

Official title: A Phase IB/II Multicenter, Two-Arm, Dose-Escalation Study of Oral AEE788 Administered in Combination With Oral RAD001 on a Continuous Once Daily Dosing Schedule in Adult Patients With First or Second Recurrent or Relapsing Glioblastoma Multiforme

Status Completed

Clinical Trial Summary

RATIONALE: AEE788 and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving AEE788 together with everolimus may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of AEE788 when given together with everolimus and to see how well they work in treating patients with recurrent or relapsed glioblastoma multiforme.

Clinical Trial Description

OBJECTIVES:

Primary

• Determine the maximum tolerated dose and dose-limiting toxicity of AEE788 when administered in combination with 1 of 2 different doses of everolimus in patients with recurrent or relapsed glioblastoma multiforme.

Secondary

• Determine the safety and tolerability of this regimen, including acute and chronic toxic effects, in these patients.

• Determine the single-dose and repeated-dose pharmacokinetic profile of this regimen in these patients.

• Determine, preliminarily, the efficacy of this regimen, in terms of response rate, progression-free survival, and overall survival, in these patients. (Phase II)

• Determine the antiangiogenic effects of this regimen in these patients.

OUTLINE: This is an open-label, multicenter, dose-escalation study of AEE788.

• Phase I: Patients are assigned to 1 of 2 treatment groups.

• Group 1: Patients receive oral AEE788 once daily and oral everolimus once daily on days 1-28.

• Group 2: Beginning at the first occurrence of dose-limiting toxicity in group 1, patients receive AEE788 as in group 1 and a higher-dose of oral everolimus once daily on days 1-28.

In both groups, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients per group receive escalating doses of AEE788 until the maximum tolerated dose is determined.

• Phase II: Patients are assigned to 1 of 2 treatment groups according to eligibility for surgery.

• Group 1 (eligible for tumor biopsy, surgical resection, or tumor debulking):

Patients receive oral AEE788 once daily at the MTD and oral everolimus once daily for 5-9 days. Patients then undergo surgery. Beginning 15-21 days after surgery, patients receive oral AEE788 and oral everolimus once daily on days 1-28.

• Group 2 (ineligible for surgery): Patients receive oral AEE788 once daily at the MTD and oral everolimus once daily on days 1-28.

In both groups, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. In both phases, if treatment with AEE788 or everolimus is stopped due to toxicity, patients may continue to receive AEE788 or everolimus alone once daily.

After the completion of study treatment, patients are followed every 3 months for as long as the investigator deems necessary. ;

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Glioblastoma
• Nervous System Neoplasms

• NCT number: NCT00107237
• Study type: Interventional
• Source: Novartis
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: October 2003
• Completion date: June 2006