Super-Selective Intraarterial Cerebral Infusion Of Temozolomide (Temodar) For Treatment Of Newly Diagnosed GBM And AA
Status:
Completed
Trial end date:
2020-08-11
Target enrollment:
Participant gender:
Summary
The high-grade malignant brain tumors, glioblastoma multiforme (GBM) and anaplastic
astrocytoma (AA), comprise the majority of all primary brain tumors in adults. This group of
tumors also exhibits the most aggressive behavior, resulting in median overall survival
durations of only 9-12 months for GBM, and 3-4 years for AA. Initial therapy has consisted of
surgical resection, external beam radiation or both. More recently, a Phase 3 clinical
published by Stupp et al in 2005 showed a benefit for using radiotherapy plus concomitant and
adjuvant Temozolomide. Still, all patients experience a recurrence after first-line therapy,
so improvements in both first-line and salvage therapy are critical to enhancing
quality-of-life and prolonging survival. It is unknown if currently used intravenous (IV)
therapies even cross the blood brain barrier (BBB). Superselective Intra-arterial Cerebral
Infusion (SIACI) is a technique that can effectively increase the concentration of drug
delivered to the brain while sparing the body of systemic side effects. One currently used
drug called Temozolomide (Temodar) has been shown to be active in human brain tumors but its
actual central nervous system (CNS) penetration is unknown. This phase I clinical research
trial will test the hypothesis that following the standard 42 day Temozolomide/radiotherapy
regimen, Temozolomide can be safely used by direct intracranial superselective intra-arterial
cerebral infusion (SIACI) up to a dose of 250mg/m2, followed by the standard maintenance
cycle of temozolomide to ultimately enhance survival of patients with newly diagnosed GBM/AA.
The investigators will determine the toxicity profile and maximum tolerated dose (MTD) of
SIACI Temozolomide. The investigators expect that this project will provide important
information regarding the utility of SIACI Temozolomide therapy for malignant gliomas, and
may alter the way these drugs are delivered to our patients in the near future.
Phase:
Phase 1
Details
Lead Sponsor:
Northwell Health
Collaborators:
Feinstein Institute for Medical Research Hofstra North Shore