Gliadel Wafer and O6-Benzylguanine in Treating Patients With Recurrent Glioblastoma Multiforme

Duke University

Status and phase

Completed

Phase 2

Conditions

Recurrent Adult Brain Tumor

Treatments

Drug: Gliadel wafers in combination with O6-benzylguanine

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00362921

CDR0000483768

DUMC-5515-04-1R0

Pro00004127

GP-DUMC-5515-06-1R2

DUMC-5515-06-1R2

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as Gliadel wafer and O6-benzylguanine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving Gliadel wafer together with O6-benzylguanine works in treating patients with recurrent glioblastoma multiforme.

Full description

OBJECTIVES:

Define the activity of Gliadel® wafers in combination with a 5-day infusion of O6-benzylguanine in patients with recurrent glioblastoma multiforme.
Define the toxicity of Gliadel® wafers in combination with 5-day infusion of O6-benzylguanine in patients with recurrent glioblastoma multiforme.

OUTLINE: This is an open-label study.

Patients undergo surgical resection of tumor followed by placement of Gliadel® wafers . Within 6 hours after completion of surgery, patients receive a 1 hour high dose infusion of O6-benzylguanine followed by a lower dose continuous infusion for 5 days. Every 48 hours a repeat infusion of the high dose over 1 hour will be administered for a total of 3 doses.

After completion of study treatment, patients are followed every 8 weeks.

PROJECTED ACCRUAL: A total of 50 patients should be accrued for this study.

Enrollment

52 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

DISEASE CHARACTERISTICS-

Histologically confirmed recurrent glioblastoma multiforme (including gliosarcoma) which can be confirmed, if not earlier, by intraoperative pathological diagnosis on frozen section
Evidence of a unilateral, single focus of measurable Central Nervous System (CNS) neoplasm on contrast-enhanced magnetic resonance imaging (MRI) or computed tomography (CT) scan that is supratentorial and measures ≥ 1.0 cm in diameter

PATIENT CHARACTERISTICS-

Greater than or equal to 18 years old
Life expectancy of greater than 12 weeks
Karnofsky performance status greater than or equal to 60%
Absolute neutrophil count ≥ 1,000/millimeters (mm)³
Platelet count ≥ 100,000/mm³
Total Serum Bilirubin < 2 times upper limit of normal (ULN)
Serum glutamic oxaloacetic transaminase (SGOT) < 3 times ULN
Blood urea nitrogen (BUN) < 1.5 times ULN
Creatinine < 1.5 times ULN
Negative pregnancy test
Recovered from any effects of major surgery
Patients or legal guardian must give written, informed consent.

PRIOR CONCURRENT THERAPY-

At least 2 weeks since prior surgical resection (if conducted) and recovered, unless there is unequivocal evidence of tumor progression
At least 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas), unless there is unequivocal evidence of tumor progression.. However, patients treated with chemotherapeutic agents such as etoposide who would normally be retreated after shorter intervals (eg, 21 days on, 7 days off schedule) may be treated at the usual starting time even if less than 4 weeks from the last prior dose of chemotherapy.

Exclusion criteria

Patients who have not recovered from surgery
Patients who are not neurologically stable for 2 weeks prior to study entry
Patients who are poor medical risks because of non-malignant systemic disease as well as those with acute infection treated with intravenous antibiotics
Frequent vomiting or medical condition that could interfere with oral medication intake (e.g., partial bowel obstruction)
Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
Known HIV positivity or AIDS-related illness
Pregnant or nursing women
Women of childbearing potential who are not using an effective method of contraception. Women of childbearing potential must have a negative serum pregnancy test 24 hours prior to administration of study drug and be practicing medically approved contraceptive precautions.
Men who are not advised to use an effective method of contraception
Patients taking immuno-suppressive agents other than prescribed corticosteroids
Patients who have had prior treatment with Gliadel Wafers.