Carmustine Followed By Surgery in Treating Patients With Recurrent Supratentorial Malignant Glioma or Metastatic Brain Neoplasm

• ClinicalTrials.gov Identifier: NCT00009854
• Recruitment Status: Unknown
• First Posted: January 27, 2003
• Last Update Posted: November 6, 2013
• Sponsor: Direct Therapeutics
• Information provided by: National Cancer Institute (NCI)

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Brain and Central Nervous System Tumors; Metastatic Cancer	Drug: carmustine in ethanol; Procedure: conventional surgery	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Primary Purpose: Treatment
• 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 Start Date: June 2000

Arms and Interventions

Outcome Measures

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, United States, 94143-0128

United States, Virginia

Massey Cancer Center

Richmond, Virginia, United States, 23298-0631

Sponsors and Collaborators

Direct Therapeutics

Investigators

• Study Chair: Gene David Resnick, MD; Millennix

More Information

• ClinicalTrials.gov Identifier: NCT00009854
• Other Study ID Numbers: CDR0000068416; DTI-0002; UCSF-H7858-17520-01; NCI-V00-1642
• First Posted: January 27, 2003
• Last Update Posted: November 6, 2013
• Last Verified: March 2003

Keywords provided by National Cancer Institute (NCI):

adult glioblastoma; tumors metastatic to brain; adult anaplastic astrocytoma; adult anaplastic ependymoma; adult anaplastic oligodendroglioma; adult giant cell glioblastoma; adult gliosarcoma

Additional relevant MeSH terms:

Neoplasms; Glioma; Nervous System Neoplasms; Central Nervous System Neoplasms; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms by Site; Nervous System Diseases; Ethanol; Carmustine; Anti-Infective Agents, Local; Anti-Infective Agents; Central Nervous System Depressants; Physiological Effects of Drugs; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents