RATIONALE: The transferrin-CRM107 immunotoxin can locate tumor cells and kill them without harming normal cells. Giving transferrin-CRM107 immunotoxin directly into the tumor may kill more tumor cells. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether transferrin-CRM107 immunotoxin is more effective than best practice chemotherapy in treating glioblastoma multiforme.

PURPOSE: Randomized phase III trial to compare the effectiveness of intratumoral transferrin-CRM107 immunotoxin with that of best practice chemotherapy in treating patients who have progressive and/or recurrent glioblastoma multiforme that cannot be surgically removed.

Condition	Treatment or Intervention	Phase
adult glioblastoma recurrent adult brain tumor adult giant cell glioblastoma adult gliosarcoma	Drug: carboplatin  Drug: carmustine  Drug: cisplatin  Drug: lomustine  Drug: nimustine  Drug: procarbazine  Drug: temozolomide  Drug: transferrin-CRM107  Drug: vincristine  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: immunotoxin therapy	Phase III

OBJECTIVES: Primary

• Compare the efficacy of intratumoral transferrin-CRM107 vs best standard chemotherapy in patients with progressive and/or recurrent unresectable glioblastoma multiforme.

Secondary

• Compare the safety of these regimens in these patients.
• Correlate the efficacy and safety of transferrin-CRM107 with the degree of transferrin receptor expression in tumor tissue and serum anti-diphtheria toxin antibody titer levels in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo stereotactic surgery to biopsy the tumor and implant 2 catheters into the tumor on day 1. Patients receive transferrin-CRM107 intratumorally continuously beginning on day 2 and continuing for 4-7 days. The catheters are then removed. Treatment repeats once 4-8 weeks later.
• Patients receive best standard of care comprising one of the following chemotherapy drugs/combinations:
• Platinum-based chemotherapy (e.g., carboplatin or cisplatin)
• Temozolomide
• Nitrosoureas (e.g., carmustine, lomustine, or nimustine)
• Procarbazine
• Procarbazine, lomustine, and vincristine Quality of life is assessed at baseline and then periodically for 6 months after the completion of study treatment.

Patients are followed monthly for 6 months and then at 9 and 12 months.

PROJECTED ACCRUAL: A total of 323 patients (215 in arm I and 108 in arm II) will be accrued for this study within 12 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed glioblastoma multiforme
• Unifocal, unilateral, and supratentorial tumor
• Progressive and/or recurrent disease confirmed by MRI
• Progressive disease, defined as ≥ 25% increase in contrast-enhanced tumor compressed spectral activity (CSA) compared to the nadir or smallest previously measured CSA
• Recurrent disease after conventional treatment, including surgery (biopsy or debulking surgery), radiotherapy, and/or chemotherapy
• Lesion must have a diameter ≥ 1.0 cm but < 4.0 cm by contrast-enhanced MRI
• Not a candidate for surgical resection
• No infratentorial or intraventricular tumors
• No satellite tumors
• No mass effect by CT scan or MRI as evidenced by any of the following:
• More than a 5 mm midline shift
• Nausea
• Vomiting
• Reduced level of consciousness
• Clinically significant papilledema

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• At least 3 months

Hematopoietic

• Platelet count ≥ 100,000/mm^3
• Absolute neutrophil count ≥ 1,000/mm^3

Hepatic

• Bilirubin ≤ 2.0 mg/dL
• AST and ALT ≤ 3 times upper limit of normal
• PT and APTT ≤ 1.5 times control

Renal

• Creatinine ≤ 1.7 mg/dL

Other

• No medical condition that would preclude anesthesia
• No severe acute infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 2 months after study treatment

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior transferrin-CRM107

Chemotherapy

• See Disease Characteristics
• More than 90 days since prior regional therapy, including administration of biodegradable polymer wafers containing carmustine
• More than 30 days since prior chemotherapy (42 days for nitrosoureas or mitomycin)
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• More than 90 days since prior radiotherapy or stereotactic (gamma knife) radiosurgery
• More than 12 months since prior brachytherapy
• No concurrent radiotherapy

Surgery

• See Disease Characteristics
• More than 30 days since prior tumor debulking or other neurosurgery
• No other concurrent surgery

Other

• More than 30 days since prior investigational agents or participation in another clinical research study
• No prior enrollment in this study
• No other concurrent anticancer drugs
• No other concurrent investigational therapies

California
      Rebecca and John Moores UCSD Cancer Center, La Jolla,  California,  92093-0658,  United States; Recruiting
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033-0804,  United States; Recruiting
Illinois
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States; Recruiting
Kentucky
      Markey Cancer Center at University of Kentucky Chandler Medical Center, Lexington,  Kentucky,  40536-0084,  United States; Recruiting
Minnesota
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States; Recruiting
New York
      University Hospital at State University of New York - Upstate Medical University, Syracuse,  New York,  13210,  United States; Recruiting
      Zalmen A. Arlin Cancer Institute at Westchester Medical Center, Hawthorne,  New York,  10532,  United States; Recruiting
North Carolina
      Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill,  North Carolina,  27599-7295,  United States; Recruiting
Pennsylvania
      Temple University Hospital, Philadelphia,  Pennsylvania,  19140,  United States; Recruiting
South Carolina
      Hollings Cancer Center at Medical University of South Carolina, Charleston,  South Carolina,  29425-0721,  United States; Recruiting
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84112,  United States; Recruiting

Study chairs or principal investigators

Patrick Rossi, MD,  Study Chair,  Xenova Biomedix   

Study ID Numbers:  CDR0000373837; KSB-311R/CIII/001; UUMC-11502
Record last reviewed:  September 2004
Record first received:  July 8, 2004
ClinicalTrials.gov Identifier:  NCT00087230
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-10