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

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ClinicalTrials.gov Identifier: NCT01180816
Recruitment Status : Active, not recruiting
First Posted : August 12, 2010
Last Update Posted : January 9, 2018
Sponsor:
Collaborators:
Feinstein Institute for Medical Research
Hofstra North Shore
Information provided by (Responsible Party):
John A. Boockvar, Feinstein Institute for Medical Research

Study Description
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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.

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

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Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : August 2010
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

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Arms and Interventions
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Arm Intervention/treatment
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)


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

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

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
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Responsible Party: John A. Boockvar, Professor, Feinstein Institute for Medical Research
ClinicalTrials.gov Identifier: NCT01180816     History of Changes
Other Study ID Numbers: 14-292A
First Posted: August 12, 2010    Key Record Dates
Last Update Posted: January 9, 2018
Last Verified: January 2018

Keywords provided by John A. Boockvar, Feinstein Institute for Medical Research:
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