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O6-Benzylguanine and Carmustine Implants in Treating Patients With Recurrent Malignant Glioma
This study has been completed.
First Received: March 7, 2000   Last Updated: February 6, 2009   History of Changes
Sponsored by: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00004892
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving drugs in different ways may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of O6-benzylguanine and implanted carmustine wafers in treating patients who have recurrent malignant glioma.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: O6-benzylguanine
Drug: polifeprosan 20 with carmustine implant
Procedure: conventional surgery
Phase I

MedlinePlus related topics: Cancer
Drug Information available for: O(6)-Benzylguanine Polifeprosan 20 Carmustine
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: Phase I GLIADEL and Continuous Infusion of Intravenous O6-Benzylguanine Trial in Patients With Recurrent Malignant Glioma

Further study details as provided by National Cancer Institute (NCI):

Study Start Date: April 2000
Detailed Description:

OBJECTIVES: I. Determine the dose of O6-benzylguanine that completely suppresses AGT levels in patients with recurrent malignant glioma. II. Evaluate the safety and tolerance of increasing duration for up to 2 weeks of continuously infused O6-benzylguanine at a dose that will completely suppress tumor AGT activity combined with intracranially implanted polifeprosan 20 with carmustine implants (Gliadel wafers) in this patient population.

OUTLINE: This is a dose escalation study of O6-benzylguanine (O6-BG). Patients in the first cohort receive O6-BG IV over 1 hour followed by continuous infusion of O6-BG for 2 days prior to surgery. Patients undergo surgical resection and receive up to 8 polifeprosan 20 with carmustine implants (Gliadel wafers) in the resected tumor cavity. Cohorts of 14 patients receive escalating doses of O6-BG until 11 out of 14 patients in a cohort have complete suppression of AGT levels. Once the dose of O6-BG that completely suppresses AGT has been established, subsequent patients receive O6-BG IV beginning at least 1 hour prior to surgery followed by the established continuous infusion dose beginning on the day of surgery. The infusion continues for up to 14 days postoperatively. Cohorts of 6-12 patients receive lengthened durations of continuous infusion O6-BG until the maximum tolerated dose (MTD) is determined or the length of the infusion reaches 14 days. The MTD is defined as the dose preceding that at which 3 of 6 or 5 of 12 patients experience dose limiting toxicities. Patients are followed at 3, 6, 9, and 12 months, and then until death.

PROJECTED ACCRUAL: A minimum of 38 patients will be accrued for this study over 9.5 months.

  Eligibility

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

DISEASE CHARACTERISTICS: Histologically confirmed malignant glioma determined from prior stereotactic biopsy or cytoreductive surgery for removal of a supratentorial brain tumor Unilateral supratentorial tumor, measuring at least 1 cm, as determined by CT scan or MRI No more than 1 focus of tumor and no tumor crossing the midline Surgical treatment indicated at baseline evaluation Received prior definitive (greater than 5,000 cGy) external beam radiotherapy more than 3 months ago Evidence of progression At time of tumor resection and Gliadel wafers implantation: Intraoperative pathological diagnosis on frozen section or squash preparation of malignant glioma OR Glioblastoma multiforme or anaplastic astrocytoma on permanent sections from a prior surgery and an intraoperative pathological diagnosis on frozen section or squash preparation of tumor, glioma, or malignant glioma (not necrosis)

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: At least 60 days Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 mg/dL Transaminases no greater than 4 times upper limit of normal Renal: Creatinine no greater than 1.7 mg/dL Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception for 1 year after surgery No other concurrent significant life threatening disease No known hypersensitivity to nitrosoureas No other malignancy in past five years except curatively treated carcinoma in situ of the cervix or basal cell carcinoma of the skin

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered No other concurrent chemotherapy during first 56 days of study Endocrine therapy: No concurrent dexamethasone as an antiemetic Radiotherapy: See Disease Characteristics Surgery: See Disease Characteristics

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00004892

Locations
United States, Alabama
University of Alabama Comprehensive Cancer Center
Birmingham, Alabama, United States, 35294
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
United States, Georgia
Emory University Hospital - Atlanta
Atlanta, Georgia, United States, 30322
United States, Maryland
Johns Hopkins Oncology Center
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
United States, Michigan
Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, North Carolina
Comprehensive Cancer Center of Wake Forest University Baptist Medical Center
Winston-Salem, North Carolina, United States, 27157-1082
United States, Pennsylvania
University of Pennsylvania Cancer Center
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78284-7811
Sponsors and Collaborators
Investigators
Study Chair: Jon Weingart, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Study ID Numbers: CDR0000067569, NABTT-9803, JHOC-NABTT-9803
Study First Received: March 7, 2000
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00004892     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent adult brain tumor
adult brain stem glioma
adult ependymoma
adult glioblastoma
adult oligodendroglioma
adult anaplastic astrocytoma
adult mixed glioma
adult giant cell glioblastoma
adult gliosarcoma

Study placed in the following topic categories:
Glioblastoma
Astrocytoma
Carmustine
Central Nervous System Neoplasms
Ependymoma
Recurrence
Brain Neoplasms
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma
O(6)-benzylguanine
Oligodendroglioma
Antineoplastic Agents, Alkylating
Glioma
Gliosarcoma
Alkylating Agents
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Neoplasms, Nerve Tissue
Nervous System Diseases
Carmustine
Enzyme Inhibitors
Central Nervous System Neoplasms
Pharmacologic Actions
Neuroectodermal Tumors
Neoplasms
Neoplasms by Site
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
O(6)-benzylguanine
Antineoplastic Agents, Alkylating
Glioma
Neoplasms, Neuroepithelial
Alkylating Agents
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on May 07, 2009