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Phase I GLIADEL and Continuous Infusion of Intravenous O6-Benzylguanine Trial in Patients With Recurrent Malignant Glioma


Phase 1
18 Years
N/A
Not Enrolling
Both
Brain and Central Nervous System Tumors

Thank you

Trial Information

Phase I GLIADEL and Continuous Infusion of Intravenous O6-Benzylguanine Trial in Patients With Recurrent Malignant Glioma


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Jon Weingart, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000067569

NCT ID:

NCT00004892

Start Date:

April 2000

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • 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
  • Glioma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms

Name

Location
University of Alabama Comprehensive Cancer Center Birmingham, Alabama  35294
H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida  33612
Emory University Hospital - Atlanta Atlanta, Georgia  30322
Johns Hopkins Oncology Center Baltimore, Maryland  21287
Comprehensive Cancer Center of Wake Forest University Baptist Medical Center Winston-Salem, North Carolina  27157-1082
University of Pennsylvania Cancer Center Philadelphia, Pennsylvania  19104
University of Texas Health Science Center at San Antonio San Antonio, Texas  78284-7811
Massachusetts General Hospital Cancer Center Boston, Massachusetts  02114
Henry Ford Hospital Detroit, Michigan  48202