Carmustine in Treating Patients With Progressive or Recurrent Glioblastoma Multiforme

A Phase I/II Study of the Safety and Tolerability of DTI-015 in Patients With 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