NCT01403610

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

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
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: The University of Texas Health Science Center at San Antonio · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Detailed 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.

Conditions

• HIGH GRADE GLIOMA

Interventions

Type	Name	Description
DRUG	TH-302 preoperative	TH-302 single dose at 575 mg/m2 administered preoperatively, followed by postoperative combination therapy bevacizumab at 10mg/kg every 2 weeks and TH-302 at 240 - 480 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.
DRUG	Placebo	Placebo administered preoperatively, followed by postoperative combination therapy bevacizumab at 10mg/kg every 2 weeks and TH-302 at 240 - 480 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.
DRUG	TH-302 (escalating) with bevacizumab 10mg/kg	Combination of 10mg/m2 of bevacizumab with an escalating dose of TH-302 from 240 to 670 mg/m2

Timeline

• Start date: 2011-06-01
• Primary completion: 2015-10-01
• Completion: 2015-10-01
• First posted: 2011-07-27
• Last updated: 2019-07-24
• Results posted: 2019-07-24

Locations

1 site across 1 country: United States