Brachytherapy in Treating Patients With Recurrent Malignant Glioma

Phase I Brachytherapy Dose Escalating Study Using the Proxima Therapeutics, Inc. GliaSite RTS in Patients With Recurrent Malignant Gliomas

RATIONALE: Brachytherapy uses radioactive material to kill cancer cells remaining after surgery.

PURPOSE: Phase I trial to study the effectiveness of brachytherapy in treating patients who have recurrent malignant glioma.

OBJECTIVES:

• Determine the maximum tolerated dose of brachytherapy using an intracavitary applicator and liquid iodine I 125 in patients with recurrent malignant glioma.
• Determine the acute and chronic toxicity of this therapy in these patients.

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

Within 3-21 days after surgical resection, patients receive brachytherapy using an intracavity balloon application (GliaSite) with iodine I 125 solution for a total of 5-7 days.

Cohorts of 5-10 patients receive escalating doses of brachytherapy until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 10 patients experience dose-limiting toxicity.

Patients are followed at 4 weeks and then every 2 months for 1 year.

PROJECTED ACCRUAL: Approximately 20-30 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant glioma

  • Anaplastic astrocytoma, anaplastic oligodendroglioma, or glioblastoma multiforme

    • Low-grade astrocytoma that progresses to high-grade astrocytoma allowed

  • Unifocal disease

  • Progressive or recurrent after radiotherapy with or without chemotherapy

    • Previously treated with at least 5,000 cGy external beam radiotherapy more than 3 months ago

• Candidate for maximal surgical resection

  • Any expected residual enhancing tumor must be within expected brachytherapy treatment volume
  • Resection must not be expected to result in a new permanent neurologic deficit

• No tumor crossing more than 1 cm beyond the midline on preoperative MRI or CT scan

• No grossly or radiographically apparent leptomeningeal spread

• No ventricular invasion outside the anticipated radiotherapy treatment volume

• No marked edema on MRI or CT scan

• Patients with 2 or more separate foci of contrast-enhancing tumors that are more than 5 cm apart on preoperative MRI or CT scan are ineligible

PATIENT CHARACTERISTICS:

Age

• 18 and over

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

Hepatic

• Not specified

Renal

• Creatinine no greater than 1.7 mg/dL
• BUN no greater than 2 times upper limit of normal

Cardiovascular

• No uncontrolled hypertension
• No unstable angina pectoris
• No uncontrolled cardiac dysrhythmia

Other

• Mini mental score at least 15
• No other medical illness that would preclude study participation
• No serious infection
• No other malignancy within the past 5 years except curatively treated carcinoma in situ of the cervix or nonmelanoma skin cancer
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent immunotherapy
• No concurrent biologic agents (e.g., immunotoxins, immunoconjugates, antiangiogenesis compounds, antisense therapy, peptide receptor antagonists, interferons, interleukins, tumor-infiltrating lymphocytes, lymphokine-activated killer cells, or gene therapy)

Chemotherapy

• See Disease Characteristics
• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas)
• No concurrent polifeprosan 20 with carmustine implant (Gliadel wafer)

Endocrine therapy

• Concurrent corticosteroids allowed to improve quality of life

Radiotherapy

• See Disease Characteristics
• No concurrent radiosurgery

Surgery

• See Disease Characteristics
• See Radiotherapy

Other

• Recovered from prior therapy
• No prior investigational agents
• No investigational agents during and for 90 days after study participation
• Concurrent cytotoxic treatment allowed to improve quality of life