Carmustine in Treating Patients With Progressive or Recurrent Glioblastoma Multiforme
Carmustine in Treating Patients With Progressive or Recurrent Glioblastoma Multiforme
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
 they stop growing or die.

 PURPOSE: Phase II trial to study the effectiveness of carmustine in treating patients who
 have progressive or recurrent glioblastoma multiforme.
OBJECTIVES:

 -  Determine the maximum tolerated dose of intratumoral carmustine in ethanol (DTI-015) in
 patients with unresectable recurrent glioblastoma multiforme. (Phase I of this study
 closed to accrual as of 01/15/2002.)

 -  Determine the qualitative and quantitative toxicity of this regimen in these patients.

 -  Assess the activity of this regimen in these patients.

 -  Estimate peripheral blood carmustine levels in these patients treated with this regimen.

 OUTLINE: This is a dose-escalation, multicenter study.

 Patients receive carmustine in ethanol (DTI-015) intratumorally over 5 minutes during
 stereotactic biopsy or open craniotomy.

 Cohorts of 3-6 patients receive escalating doses of DTI-015 until the maximum tolerated dose
 (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 patients
 experience dose-limiting toxicity. (Phase I of this study closed to accrual as of
 01/15/2002.)

 Additional patients then receive treatment with DTI-015 at the recommended phase II dose.

 Patients are followed at 4, 8, and 12 weeks and then every 1-3 months until disease
 progression.

 PROJECTED ACCRUAL: A total of 12 patients were accrued for phase I of this study and
 approximately 14-18 patients will be accrued for phase II of this study. (Phase I of this
 study closed to accrual as of 01/15/2002.)
DISEASE CHARACTERISTICS:

 -  Histologically proven supratentorial malignant glioblastoma multiforme

 -  Clear evidence of disease progression by MRI

 -  Unresectable tumor that has spherical, spheroid, or ovoid shape (not multicentric
 or multilobulated)

 -  Central necrosis and/or central cystic areas allowed in the presence of enhancing
 rim thickness greater than 5 mm

 -  No brainstem (pons or medulla) or midbrain (mesencephalon) involvement

 -  No involvement of primary sensorimotor cortex in the dominant hemisphere or
 within 1.5 cm of the optic chiasm, either optic nerve, or any other cranial nerve

 -  No tumor extension into the ventricular system

 -  Tumor volume no greater than 33.4 cm3

 -  At least one prior radiotherapy

 PATIENT CHARACTERISTICS:

 Age:

 -  18 to 75

 Performance status:

 -  Karnofsky 60-100%

 Life expectancy:

 -  Not specified

 Hematopoietic:

 -  Absolute neutrophil count at least 1,500/mm^3

 -  Platelet count at least 100,000/mm^3

 -  No evidence of bleeding diathesis

 Hepatic:

 -  Bilirubin no greater than 2.0 mg/dL

 -  SGOT/SGPT no greater than 2.5 times normal

 Renal:

 -  Creatinine no greater than 2.0 mg/dL OR

 -  Creatinine clearance at least 40 mL/min

 -  BUN no greater than 30 mg/dL

 Other:

 -  Not pregnant or nursing

 -  Negative pregnancy test

 -  Fertile patients must use effective contraception

 -  No active uncontrolled infection

 -  Afebrile unless fever due to presence of tumor

 -  No other concurrent serious medical or psychiatric illness that would preclude study

 PRIOR CONCURRENT THERAPY:

 Biologic therapy:

 -  Not specified

 Chemotherapy:

 -  At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin
 including Gliadel wafer therapy) and recovered

 Endocrine therapy:

 -  Not specified

 Radiotherapy:

 -  See Disease Characteristics

 -  At least 4 weeks since prior radiotherapy and recovered

 -  No prior intracranial brachytherapy

 Surgery:

 -  Recovered from any prior surgery

 Other:

 -  No prior anticoagulants

 -  No other concurrent investigational agents