RATIONALE: Monoclonal antibodies can locate tumor cells and deliver radioactive tumor-killing substances such as radioactive iodine to them without harming normal cells.

PURPOSE: Randomized phase I/II trial to compare two methods of delivering radiolabeled monoclonal antibody therapy to patients with primary brain tumors.

Condition	Treatment or Intervention	Phase
adult brain tumor	Drug: iodine I 131 monoclonal antibody 81C6  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: conventional surgery  Procedure: isotope therapy  Procedure: monoclonal antibody therapy  Procedure: radiation therapy  Procedure: radioimmunotherapy  Procedure: surgery	Phase I Phase II

Further Study Details: 

OBJECTIVES:

• Determine which one of two delivery techniques (bolus injection versus microinfusion) provides the greater distribution volume of iodine I 131 antitenascin monoclonal antibody 81C6 (I 131 MAb 81C6) administered intratumorally in patients with newly diagnosed or recurrent malignant primary brain tumors.
• Determine the maximum tolerated dose of I 131 MAb 81C6 delivered intratumorally in these patients.
• Evaluate the efficacy of I 131 MAB 81C6 delivered intratumorally in these patients.

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

Patients are randomized to receive iodine I 131 antitenascin monoclonal antibody 81C6 (I 131 MAb 81C6) by one of two delivery techniques first, then crossover to receive the antibody by the other technique 3 days later. Each patient then receives a therapeutic dose by the most efficient method. Both methods are delivered via a stereotactically-placed intralesional catheter.

• Arm I: Bolus injection method
• Arm II: Microinfusion delivery method Cohorts of 3-6 patients receive escalating doses of I 131 MAb 81C6, with dose escalation occurring separately for each arm. After 10 patients are enrolled and the best method of administration is determined, all subsequent patients receive I 131 MAb 81C6 by that method, and the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more the 2 of 6 patients experience dose-limiting toxicity.

Patients with newly diagnosed tumors for which no effective conventional therapy exists, such as malignant glial tumors, are treated with external beam radiotherapy within 4 months after I 131 MAb 81C6 infusion. Patients with recurrent tumors receive no other therapy unless tumor progresses.

Patients are followed at 4, 8, 16, and 24 weeks and then every 12 weeks for one year.

PROJECTED ACCRUAL: At least 10 patients will be accrued for this study within 1 year.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically proven newly diagnosed or recurrent primary intracranial WHO grade III or IV glioma
• Reactivity of tumor cells with 81C6 demonstrated by immunohistology with either a polyclonal rabbit antibody or the monoclonal mouse antibody
• Radiographic evidence of a single lesion by MRI or CT scan
• No greater than 2 to 5 cm
• No cerebral herniation syndrome
• Midline brain shift less than 0.5 cm

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count greater than 1000/mm^3
• Platelet count greater than 100,000/mm^3
• Hemoglobin greater than 10 g/dL

Hepatic:

• Bilirubin less than 1.5 mg/dL
• Alkaline phosphatase less than 1.5 times normal
• SGOT less than 1.5 times normal

Renal:

• Creatinine less than 2.0 mg/dL

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No allergies to iodine or local anesthetics

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No concurrent autologous bone marrow transplant

Chemotherapy:

• No more than 1 prior conventional or phase II chemotherapy regimen
• No prior phase I chemotherapy regimens
• At least 4 weeks since prior chemotherapy
• No concurrent systemic chemotherapy

Endocrine therapy:

• Corticosteroids allowed but must be on stable dose for at least 1 week

Radiotherapy:

• At least 3 months since radiotherapy to site of measurable disease in the nervous system, unless evidence of progression

Surgery:

• Not specified

North Carolina
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States

Study chairs or principal investigators

Darell D. Bigner, MD, PhD,  Study Chair,  Duke Comprehensive Cancer Center   

Study ID Numbers:  CDR0000066515; DUMC-1529-01-8R4; DUMC-1363-97-9; DUMC-1409-98-9R1; DUMC-1529-00-8R3; DUMC-1630-99-9R2; DUMC-97112; NCI-5950NS20023; NCI-G98-1471; NCT00003478
Record last reviewed:  February 2005
Last Updated:  February 8, 2005
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003478
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08