Trial Of Super-Selective Intraarterial Cerebral Infusion Of Temozolomide (TEMODAR) For Treatment Of Newly Diagnosed Glioblastoma Multiforme And Anaplastic Astrocytoma

This study is currently recruiting participants.
Verified December 2012 by Weill Medical College of Cornell University
Information provided by (Responsible Party):
John A. Boockvar, Weill Medical College of Cornell University Identifier:
First received: August 10, 2010
Last updated: December 18, 2012
Last verified: December 2012

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

Resource links provided by NLM:

Further study details as provided by Weill Medical College of Cornell University:

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 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Temodar Drug: Super-Selective Intraarterial Intracranial Infusion of Temozolomide
This phase I clinical research trial will test the hypothesis that temozolomide can be safely used by direct intracranial superselective intraarterial infusion up to a dose of 250mg/m2 to ultimately enhance survival of patients with newly diagnosed GBM/AA.

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Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

A. Criteria for Inclusion:

  1. Male or female patients of =>18 years of age.
  2. Patients with a newly documented histologic diagnosis of glioblastoma multiforme (GBM), anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma (AOA).
  3. 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., Gd-enhanced MRI or CT scans) documenting existing lesions must have been performed within three weeks of treatment on this research study.
  4. Patients must have a Karnofsky performance status =>60% (or the equivalent ECOG level of 0-2) (see Appendix A; Performance Status Evaluation) and an expected survival of => three months.
  5. No chemotherapy for two weeks prior to treatment under this research protocol and no external beam radiation for two weeks prior to treatment under this research protocol.
  6. 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
  7. 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.
  8. Pre-enrollment coagulation parameters (PT and PTT) must be <=1.5X the IUNL. Patients taking Coumadin must have an INR less than 2.0.
  9. 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. We do not believe that study procedures place subjects with increased intracranial pressure at any additional risk.

  10. Study Specific: Patients on enzyme-inducing anticonvulsants or non-enzyme inducing anticonvulsants will be allowed in the study. Patients receiving proton pump inhibitor or H2 blockers will be allowed in the study. Patients taking antacids will be allowed in the study.
  11. Patients who experience dose delays or interruptions in first 42 days of treatment will still be eligible for the one time dose of SIACI Temozolomide
  12. 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.
  13. 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.
  14. Patients on steroids must receive prophylaxis for PCP pneumonia with Bactrim, unless they have a history of allergy to sulfa drugs in which case, alternate prophylaxis will be used.
  15. Patients able to understand and give written informed consent and those patients that are cognitively impaired (which is common in GBM) are eligible for the trial. Informed consent must be obtained at the time of patient screening (prior to Day 0 of the procedure) either by the patient or a legalized authorized representative (LAR) of the patient (healthcare proxy). All subjects must ascent to therapy. If they are able to understand and provide written informed consent, then consent must be obtained from the Legally Authorized Representative (LAR)

Exclusion Criteria:

- 1. Women who are pregnant or lactating.

2. 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
Please refer to this study by its identifier: NCT01180816

Contact: John Boockvar, MD 212-746-1996

United States, New York
Weill Cornell Medical College Department of Neurological Surgery Recruiting
New York, New York, United States, 10710
Contact: John Boockvar, MD    212-746-1996   
Contact: Trisha Ali-Shaw    212-746-7373   
Principal Investigator: John Boockvar, MD         
Sub-Investigator: Ehud Lavi, MD         
Sub-Investigator: Pierre Gobin, MD         
Sub-Investigator: Athos Patsalides, MD         
Sub-Investigator: Susan C. Pannullo, MD         
Sub-Investigator: Philip Stieg, PhD, MD         
Sub-Investigator: Theodore Schwartz, MD         
Sub-Investigator: Kane Prior, MD         
Sub-Investigator: Ronald Scheff, MD         
Sponsors and Collaborators
Weill Medical College of Cornell University
  More Information

No publications provided

Responsible Party: John A. Boockvar, Associate Professor, Weill Medical College of Cornell University Identifier: NCT01180816     History of Changes
Other Study ID Numbers: 0912010814
Study First Received: August 10, 2010
Last Updated: December 18, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Weill Medical College of Cornell University:

Additional relevant MeSH terms:
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses processed this record on April 17, 2014