Clinical trial NCT00006656: Carmustine in Treating Patients With Progressive or Recurrent Glioblastoma Multiforme
Official title: A Phase I/II Study of the Safety and Tolerability of DTI-015 in Patients With Recurrent Glioblastoma Multiforme
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Brain and Central Nervous System Tumors
Keywords: recurrent adult brain tumor
adult glioblastoma
adult giant cell glioblastoma
adult gliosarcoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.)

Eligibility criteria: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: San Francisco
country: United States
facility: UCSF Cancer Center and Cancer Research Institute
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Denver
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital - Atlanta
state: Georgia
city: Evanston
country: United States
facility: Evanston Northwestern Health Care
state: Illinois
city: Edison
country: United States
facility: John F. Kennedy Medical Center
state: New Jersey
city: Cincinnati
country: United States
facility: Barrett Cancer Center
state: Ohio
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: Richmond
country: United States
facility: Massey Cancer Center
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Millennix
name: Gene David Resnick, MD
role: STUDY_CHAIR
References: