Safety and Efficacy Study of TH-302 CNS Penetration in Recurrent High Grade Astrocytoma Following Bevacizumab

HIGH GRADE GLIOMA Clinical Trial

Official title: A Phase 2, Investigator Initiated Study to Determine the Safety, Efficacy and CNS Penetration of TH-302 in Recurrent High Grade Astrocytoma Following Bevacizumab

Status Completed

Clinical Trial Summary

The Primary Objectives are:

• To determine the extent by which TH-302 is able to penetrate the blood brain barrier and affect tumor tissue

• To assess the safety of single dose TH-302 in patients with high grade glioma undergoing surgery

• To assess the safety of TH-302 in combination with bevacizumab for patients with high grade glioma

• To determine the MTD and DLT(s) of TH-302 in combination with bevacizumab

The Secondary Objectives are:

To determine the progression-free survival with or without debulking craniotomy for patients treated with combination bevacizumab and TH-302 following recurrence on single agent bevacizumab

Clinical Trial Description

Single center, dose-escalation, prospective study with TH-302 single dose at 575 mg/m2 or placebo administered preoperatively, followed by postoperative combination therapy bevacizumab at 10mg/kg every 2 weeks and TH-302 at 240 - 670 mg/m2 every 2 weeks (4 week cycle) until disease progression. Subjects will be randomized (2:1) to receive pre-operative dose of TH-302 (surgical subjects only). Subjects not receiving surgery will receive combination therapy of bevacizumab at 10 mg/kg every 2 weeks and TH-302 at 240-670 mg/m2 every 2 weeks (4 week cycle) starting from Cycle 1, Day 1 until disease progression.

This study will use a classic dose escalation design to determine the MTD of TH-302 when used in combination with bevacizumab. The dose of TH-302 will be escalated in cohorts of 3-6 subjects. The initial dose of TH-302 will be 240 mg/m2. A dose level minus 1 will be built into the study in the event that subjects experience excessive toxicity at Dose Level 1. Dose escalation will continue to 340 mg/m2 and 670 mg/m2. ;

Related Conditions & MeSH terms

• Astrocytoma
• Glioma
• HIGH GRADE GLIOMA

• NCT number: NCT01403610
• Study type: Interventional
• Source: The University of Texas Health Science Center at San Antonio
• Status: Completed
• Phase: Phase 2
• Start date: June 2011
• Completion date: October 2015