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

NCT01180816 | Completed Phase 1

• 1 other identifier: 14-292A
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Glioblastoma Multiforme; Anaplastic Astrocytoma

Keywords

GBM; AA; AO; Brain; Tumors; Malignant; Glioblastoma; Multiforme; Anaplastic; Astrocytoma

Outcome Measures

Primary Outcomes (1)

• Determine the safety of superselective intra-arterial cerebral infusion of Temozolomide up to a dose of 250 mg/m2 IA.

  2 years

Secondary Outcomes (2)

• Composite overall response rate.

  2 years

• Six-month progression-free survival (PFS) and overall survival (OS)

  throughout the study.

Study Arms (1)

Temozolomide (Temodar)

EXPERIMENTAL

Drug: Super-Selective Intraarterial Intracranial Infusion of Temozolomide

Interventions

Super-Selective Intraarterial Intracranial Infusion of Temozolomide DRUG

A single dose of Intraarterial Mannitol to open the blood brain barrier followed by Intra-arterial Temozolomide single dose (starting at 75mg/m2 and up to 250mg/m2)

Temozolomide (Temodar)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients of ≥18 years of age.
• Patients with a documented histologic diagnosis of newly diagnosed or glioblastoma multiforme (GBM), anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma (AOA).
• Patients must have at least one confirmed and evaluable tumor site.∗
• \*A confirmed tumor site is one in which is biopsy-proven. NOTE: Radiographic procedures (e.g., Gad-enhanced MRI or CT scans) documenting existing lesions must have been performed within three weeks of treatment on this research study.
• Patients must have a Karnofsky performance status ≥60% (or the equivalent ECOG level of 0-2) and an expected survival of ≥ three months.
• No other chemotherapy for two weeks prior to treatment under this research protocol
• Patients must have adequate hematologic reserve with WBC≥3000mm3, absolute neutrophils ≥1500mm3 and platelets ≥100,000 mm3. Patients who are on Coumadin must have a platelet count of ≥150,000 mm3
• Pre-enrollment chemistry parameters must show: bilirubin\<1.5X the institutional upper limit of normal (IUNL); AST or ALT\<2.5X IUNL and creatinine\<1.5X IUNL.
• Pre-enrollment coagulation parameters (PT and PTT) must be ≤1.5X the IUNL.
• Concomitant Medications:
• Growth factor(s): Must not have received within 1 week of entry onto this study.
• Steroids: Systemic corticosteroid therapy is permissible in patients with CNS tumors for treatment of increased intracranial pressure or symptomatic tumor edema. Patients with CNS tumors who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to study entry.
• Patients must agree to use a medically effective method of contraception during and for a period of three months after the treatment period. A pregnancy test will be performed on each premenopausal female of childbearing potential immediately prior to entry into the research study.
• Patients on steroids must receive prophylaxis for PCP pneumonia with Bactrim, unless they have a history of allergy to sulfa drugs.
• Patients must be able to understand and give written informed consent. Informed consent must be obtained at the time of patient screening.

You may not qualify if:

• Women who are pregnant or lactating.
• Subjects who decline birth control. Women of childbearing potential and fertile men will be informed as to the potential risk of procreation while participating in this research trial and will be advised that they must use effective contraception during and for a period of three months after the treatment period.
• Patients with significant intercurrent medical or psychiatric conditions that would place them at increased risk or affect their ability to receive or comply with treatment or post-treatment clinical monitoring.

Sponsors & Collaborators

• Northwell Health: lead
• Feinstein Institute for Medical Research: collaborator
• Hofstra North Shore: collaborator

Study Sites (1)

Lenox Hill Brain Tumor Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Glioblastoma; Astrocytoma; Neoplasms

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 10, 2010
• First Posted: August 12, 2010
• Study Start: August 1, 2010
• Primary Completion: December 1, 2017
• Study Completion: August 11, 2020
• Last Updated: March 4, 2021

Record last verified: 2021-03

Locations

US (1)