Clinical Trial: Super-Selective Intraarterial Cerebral Infusion Of Temozolomide (Temodar) For Treatment Of Newly Diagnosed GBM And AA

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Phase I Trial of Super-Selective Intraarterial Cerebral Infusion of Temozolomide (Temodar) for Treatment of Newly Diagnosed Glioblastoma Multiforme and Anaplastic Astrocytoma

Brief 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 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.

Detailed Summary:

The current standard of care for newly diagnosed GBM is radiation therapy plus concomitant oral Temozolomide of doses of 75mg/m2 up to 150mg/m2. Because of the blood brain barrier (BBB) where drugs do not penetrate the blood vessel walls well to get into the brain, no one knows for sure if these oral drugs actually get into the brain after infusion. Previous studies have shown that intra-carotid artery (intra-arterial) delivery is superior to standard intravenous or oral delivery for increasing the penetration of drug to the brain. Previous techniques using intra arterial (intracarotid) infusion still were non-selective as drug delivery still went to all blood vessels in the brain, so patients still had significant adverse events, such as blindness. Newer techniques in interventional neuroradiology have allowed for a more selective delivery of catheters into the arterial tree where chemotherapies can be delivered without the risk of adverse affects such as blindness. Therefore, this trial will ask one simple question: Is it safe to deliver a dose of Temozolomide intrarterially using these super selective delivery techniques in addition to the standard oral route of administration? This should not only increase the amount of drug that gets to the tumor but also spare the patient many of the adverse effects from a less selective delivery. Prior to this single dose of intra-arterial Temozolomide, the patient will also receive a dose of mannitol that will increase the permeability of the blood brain barrier to improve delivery of the agent to the brain. After this single dose of mannitol and Temozolomide, the patient will be evaluated for 4 weeks to assess for toxicity. If there is no toxicity at this point, then the patient will proceed with oral maintenance Temozolomide chemotherapy. In summary, this is a Phase I trial that is designed to test the safety of a single dose of intra-arterial delivery of Temozolomide immediate
Sponsor: Northwell Health

Current Primary Outcome: Determine the safety of superselective intra-arterial cerebral infusion of Temozolomide up to a dose of 250 mg/m2 IA. [ Time Frame: 2 years ]

Original Primary Outcome: To determine the safety of superselective intra-arterial cerebral infusion of Temozolomide up to a dose of 250mgm2 IA. [ Time Frame: 2 years ]

Current Secondary Outcome:

  • Composite overall response rate. [ Time Frame: 2 years ]
  • Six-month progression-free survival (PFS) and overall survival (OS) [ Time Frame: throughout the study. ]


Original Secondary Outcome:

  • Composite overall response rate: The composite overall response rate (CORR) will be examined. The overall response proportion along with a 95% confidence interval will be estimated via binomial proportions. [ Time Frame: 2 years ]
  • Six-month progression-free survival (PFS) and overall survival (OS) will be assessed by Kaplan-Meier survival analysis, assuming adequate follow-up time. [ Time Frame: 6 months ]
    PFS will be measured from the date of the first dose of Temozolomide to the date of progression. OS will be measured from the date of the first dose of Temozolomide to the date of death. A two-year follow-up time is expected.


Information By: Northwell Health

Dates:
Date Received: August 10, 2010
Date Started: August 2010
Date Completion: December 2017
Last Updated: January 30, 2017
Last Verified: January 2017