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

Purpose

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.

Condition	Intervention	Phase
Glioblastoma Multiforme Anaplastic Astrocytoma	Drug: Super-Selective Intraarterial Intracranial Infusion of Temozolomide	Phase 1


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I Trial of Super-Selective Intraarterial Cerebral Infusion of Temozolomide (Temodar) for Treatment of Newly Diagnosed Glioblastoma Multiforme and Anaplastic Astrocytoma

Resource links provided by NLM:

Drug Information available for: Temozolomide

Genetic and Rare Diseases Information Center resources: Glioblastoma Anaplastic Astrocytoma Glioma Neuroepithelioma

U.S. FDA Resources

Further study details as provided by Northwell Health:

Primary Outcome Measures:

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

Secondary Outcome Measures:

Composite overall response rate. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Six-month progression-free survival (PFS) and overall survival (OS) [ Time Frame: throughout the study. ] [ Designated as safety issue: No ]


Estimated Enrollment:	30
Study Start Date:	August 2010
Estimated Study Completion Date:	December 2016
Estimated Primary Completion Date:	December 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Temozolomide (Temodar)	Drug: Super-Selective Intraarterial Intracranial Infusion of Temozolomide 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)

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Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Criteria for Inclusion:

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.

Exclusion Criteria:

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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01180816

Locations


United States, New York
Lenox Hill Brain Tumor Center
New York, New York, United States, 10065

Sponsors and Collaborators

Northwell Health

Feinstein Institute for Medical Research

Hofstra North Shore

More Information


Responsible Party:	John A. Boockvar, Professor, Feinstein Institute for Medical Research
ClinicalTrials.gov Identifier:	NCT01180816 History of Changes
Other Study ID Numbers:	14-292A
Study First Received:	August 10, 2010
Last Updated:	January 12, 2016
Health Authority:	United States: Food and Drug Administration

Keywords provided by Northwell Health:


GBM AA AO Brain Tumors	Malignant Glioblastoma Multiforme Anaplastic Astrocytoma

Additional relevant MeSH terms:


Glioblastoma Astrocytoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms	Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Temozolomide Dacarbazine Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents

ClinicalTrials.gov processed this record on September 23, 2016