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	Treatment or Intervention	Phase
Adult Oligodendroglioma recurrent adult brain tumor adult glioblastoma multiforme adult ependymoma adult anaplastic astrocytoma adult brain stem glioma Mixed Gliomas	Drug: O6-benzylguanine  Drug: polifeprosan 20 with carmustine implant	Phase I

Further Study Details: 

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.

PROTOCOL 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.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY 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)

--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

--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

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

Study chairs or principal investigators

Jon Weingart,  Study Chair,  Johns Hopkins Oncology Center   

Study ID Numbers:  CDR0000067569; JHOC-NABTT-9803; NABTT-9803
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  March 7, 2000
ClinicalTrials.gov Identifier:  NCT00004892
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08