Clinical trial NCT00009854: Carmustine Followed By Surgery in Treating Patients With Recurrent Supratentorial Malignant Glioma or Metastatic Brain Neoplasm
Official title: Phase I/II Study of Intratumoral Injection of DTI-015 Prior to Tumor Resection in Patients With Recurrent Malignant Glioma or Metastatic Neoplasm to Brain
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Brain and Central Nervous System Tumors
Metastatic Cancer
Keywords: adult glioblastoma
tumors metastatic to brain
adult anaplastic astrocytoma
adult anaplastic ependymoma
adult anaplastic oligodendroglioma
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 I/II trial to study the effectiveness of carmustine followed by surgery in treating patients who have recurrent supratentorial malignant glioma or metastatic brain neoplasm.

Detailed description: OBJECTIVES:

* Determine the extent and pattern of distribution of DNA adducts in patients with recurrent supratentorial malignant glioma or metastatic neoplasm to the brain treated with neoadjuvant intratumoral carmustine in ethanol (DTI-015) followed by tumor resection.
* Determine the qualitative and quantitative toxicity of this treatment regimen in these patients.

OUTLINE: This is a dose escalation study.

Patients receive neoadjuvant carmustine in ethanol (DTI-015) intratumorally under stereotactic guidance 45-90 minutes prior to craniotomy and tumor resection.

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 3 or 3 of 6 patients experience dose-limiting toxicity.

Patients are followed at 4, 8, and 12 weeks, and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed recurrent supratentorial malignant glioma with clear evidence of progression by MRI

  * Glioblastoma multiforme
  * Anaplastic ependymoma
  * Anaplastic astrocytoma
  * Anaplastic oligodendroglioma OR
* Metastatic tumor to the brain other than melanoma
* Planned resection of tumor (must be first surgery for recurrent disease)
* Tumor volume of each tumor component or residual tumor must be at least 4 cm3 and no greater than 33.4 cm3
* Tumor shape and surrounding structure(s) unlikely to cause an irregular distribution of the injected study drug

  * Tumor is spherical, spheroid, or ovoid
  * No tumors shaped into 3 or more components (e.g., multicentric or multilobulated)
  * No tumors extending into the ventricular system
  * Tumor has an intact stroma (i.e., tumor mass not partially incised or punctured)
  * Central necrosis and/or central cystic areas allowed if an enhancing rim with a thickness of more than 5 mm is present
* No tumors in the following locations of the brain:

  * Brainstem (pons or medulla)
  * Midbrain (mesencephalon)
  * Primary sensorimotor cortex in the dominant hemisphere
  * Within 1.5 cm of the optic chiasm, either optic nerve, or any other cranial nerve

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 and 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 OR
* BUN no greater than 30 mg/dL

Other:

* No active uncontrolled infection
* Afebrile (37.5 degrees C) unless fever due to tumor
* No other unstable or severe medical condition
* No complicating medical or psychiatric problem that would preclude study
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* At least 4 weeks since prior systemic chemotherapy (6 weeks for nitrosoureas, mitomycin, or Gliadel wafers) and recovered
* No anti-tumor chemotherapy within 12 weeks after study drug unless tumor volume increases by more than 25% by MRI

Endocrine therapy:

* Not specified

Radiotherapy:

* At least 4 weeks since prior radiotherapy and recovered
* No prior intracranial brachytherapy
* No anti-tumor radiotherapy within 12 weeks after study drug unless tumor volume increases by more than 25% by MRI

Surgery:

* See Disease Characteristics
* Prior surgery allowed
* No anti-tumor surgery within 12 weeks after study drug

Other:

* No concurrent anticoagulants
* No other concurrent investigational agents

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Cancer Center and Cancer Research Institute
state: California
city: Richmond
country: United States
facility: Massey Cancer Center
state: Virginia
Study officials:
affiliation: Millennix
name: Gene David Resnick, MD
role: STUDY_CHAIR
References: