NCT00859222

LBH589 and Bevacizumab in Patients With Recurrent High Grade Glioma

Phase I/II Study of LBH589 and Bevacizumab in Patients With Recurrent High Grade Glioma

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 51 (actual)
• Sponsor: Patrick Y. Wen, MD · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this research study is to determine the amount of LBH589 that can be given to people safely when LBH589 is given in combination with bevacizumab. LBH589 in combination with bevacizumab is a drug combination that may stop cancer cells from growing abnormally. LBH589 has been used alone in other trials for solid tumor malignancies. Bevacizumab is FDA approved for use in patients with colorectal cancer and has been studied extensively in other types of solid tumors. The combination of LBH589 and bevacizumab has not yet been studied but information from other studies suggests that the combination may help prevent the growth of the participant's tumor.

Detailed description

Phase I Primary Objective • To determine the maximum tolerated dose (MTD) of LBH589 in combination with bevacizumab given at 10 mg/kg every 2 weeks in patients with recurrent glioblastoma (GBM), gliosarcoma, anaplastic astrocytoma, anaplastic oligodendroglioma or mixed anaplastic oligoastrocytoma. Secondary Objective • To define safety. Phase II Primary Objective • To determine the efficacy of LBH589 in combination with bevacizumab in patients with recurrent GBM or gliosarcoma as measured by 6-month progression-free survival (PFS6). Secondary Objectives * To measure overall survival, time-to-tumor progression and objective tumor response. * To further evaluate safety. Exploratory Objectives * To provide preliminary data on the efficacy in patients with recurrent anaplastic astrocytoma, anaplastic oligodendroglioma or mixed anaplastic oligoastrocytoma. * To explore the relationship of the molecular phenotype of the tumor with survival. * To investigate correlation of treatment response with laboratory correlates including, plasma angiogenic proteins and perfusion MRI. Statistical Design The Phase I study follows a standard 3+3 dose escalation design. Three potential dose levels of oral LBH589 3x per week days 1, 3 and 5 are under evaluation including a starting dose 0 on a weekly schedule as well as dose level 2 and a de-escalation dose level 1 on a weekly schedule. \[Note: The study was amended to revise the starting dose due to concerns for thrombocytopenia with the weekly dosing regimen.\] The DLT observation period is the first 30 days of treatment. For the Phase II study, based on prior research of bevacizumab monotherapy, a PFS6 rate of 35% does not justify further utilization of LBH589 in combination with bevacizumab while a PFS6 rate of 55% is worthy of further study. With 41 GBM eligible participants in the Phase II study, the treatment would be deemed promising if at least 20 GBM participants achieve 6-month progression-free survival. This design has at least 85% power and a 0.07 significance level to predict the difference between the null hypothesis of 35% PFS6 rate and the alternative hypothesis of 55% PFS6 rate. The protocol specifies a planned interim analysis after the first 21 participants have been accrued. If 12 or more of those participants have died or experienced disease progression/ relapse within 6 months of initiating treatment, accrual will be suspended and the data carefully reviewed before proceeding with additional patient accrual. Participants who are removed from active treatment for toxicity prior to reaching 6 months on treatment are not included in this interim analysis. Participants with recurrent GBM enrolled in the phase I study at the maximum tolerated dose (ie, the phase II dose) are eligible for inclusion in the interim analysis.

Conditions

• Malignant Glioma

Interventions

Type	Name	Description
DRUG	LBH589
DRUG	bevacizumab

Timeline

• Start date: 2009-03-01
• Primary completion: 2013-09-01
• Completion: 2015-12-01
• First posted: 2009-03-10
• Last updated: 2017-03-14
• Results posted: 2016-11-28

Locations

5 sites across 1 country: United States